ABSTRACT BOOK

17 th INTERNATIONAL CONFERENCE
ON PHOSPHORUS CHEMISTRY
(ICPC-17)
ABSTRACT BOOK
April 15 - 19, 2007
Xiamen, China

Plenary Lecture
INDEX
PL-1 Structure and reactivity of inorganic phosphorus compounds Francois Mathey······································ 1
PL-2 Phosphate - the cornerstone of life G. Micheal Blackburn············································································· 2
Symposium 1
PHOSPHORUS IN ORGANIC SYNTHESIS & STEREOCHEMISTRY; STRUCTURE AND
REACTIVITY OF ORGANOPHOSPHORUS COMPOUNDS
KL-1 Chemistry of carbaphosphatranes Takayuki Kawashima·············································································· 5
KL-2 Development methods synthesis of polyheterophosphacyclanes with endocyclic P-C bond on the
basis of functionalized alkylphosphonates(-phosphinates) M.A.Pudovik, N.A.Khailova,
R.Kh.Bagautdinova, S.A.Terent’eva, L.K.Kibardina································································································· 6
KL-3 Rings and cages derived from phospha-alkynes John Nixon ···································································· 7
IL-1 Metal-mediated P-H addition as a powerful tool for the construction of C-P bonds: from
academic interests to practical applications Li-Biao Han ········································································· 8
IL-2 New synthetic approaches to the chiral cyclic and macrocyclic phosphine ligands O.G.Sinyashin,
A.A.Karasik, E.Hey-Hawkins································································································································10
O-1 Synthesis and properties of λ 5 -phosphinines and λ 5 -azaphosphinines Aleksandr N.Kostyuk,
Yurii V.Svyashchenko, Dmitrii M.Volochnyuk, Dmitrii A.Sibgatulin, Aleksandr M.Pinchuk·······································12
O-2 The synthesis and spectroscopic properties of spiro-ansa-spiro phosphazenes Amgalan Natsagdorj,
Selen Bilge, Semsay Demiriz, Zeynel Kilic·············································································································13
O-3 Acetylenephosphonates: reactions with nucleophiles B.I. Ionin, A.V. Dogadina, A.V. Aleksandrova
N.G. Didkovskii ···················································································································································14
O-4 New insights in P-nucleophile addıtıons onto unsaturated imino derivatıves for the synthesıs of
P-analogues of glutamıc acid Christian V. Stevens, Kristof Moonen, Ellen Van Meenen ·························15
O-5 A facile and highly efficient method for α-amino phosphonates via three-component reactions
from aryl azides catalyzed by iron-iodine in the absence of solvent You Huang, Yaqin Yu,
Tanglin Liu, Dexin Feng, Ruyu Chen ····················································································································16
O-6 Reaction mechanism studies of solvolytic displacement of chloride from phosphorus Dennis N. Kevill,
Han Joong Koh, Suk Jin Kang ······························································································································17
O-7 The new tipe of calix[4]resorcines bearing phosphonates and phosphonium fragments at the
lower rim E.L. Gavrilova, A.A. Naumova, N.I. Shatalova, A.R. Burilov, M.A. Pudovik, E.A. Krasil’nikova,
A.I. Konovalov·····················································································································································18
O-8 Microbial resolution of racemic phosphonates derivatives with one or two stereogenic centres
Ewa Żymańczyk-Duda, Małgorzata Brzezińska-Rodak, Magdalena Klimek-Ochab, Renata Kuriata, Marta Miszuk,
Paweł Kafarski, Barbara Lejczak··························································································································19
I

O-9 Advantages of organophosphorus synthesis in ionic liquids:“Green” approaches to useful
phosphorus substituted building-blocks I. L. Odinets, E.V. Matveeva, E. V.Sharova, O. I.Artyushin,
V.A.Kozlov, D.V. Vorob’eva, S. N. Osipov, T. A. Mastryukova, G.-V. Röschenthaler ················································20
O-10 Synthesis and chemical properties of benzo[e]-1,2-oxaphosphorinine derivatives – P-analogues of
coumarines E.N.Varaksina, D.A.Tatarinov, K.Yu.Cherkin, V.F.Мironov, A.I.Konovalov ··································21
O-11 The reaction of 1,2-naphthoquinones with some P(III) derivatives – a versatile sythetic
approach to potentially useful naphthoquinones and dihydroxynaphthale-nes containing
phosphorus–carbon bond A.V.Bogdanov, V.F.Мironov, N.R.Khasiyatullina, D.B.Krivolapov ···················22
O-12 Ylides and carbenes. The first carbene catalyzed reaction Shevchenko I.V., Rogalyov A.E.,
Poliakov D.V., Röschenthaler G.-V. ······················································································································23
O-13 Synthesis, optical properties and reactivities of a dibenzophosphaborin and its derivatives
Junji Kobayashi, Tomohiro Agou, and Takayuki Kawashima··················································································24
O-14 Phosphinous acid-boranes:an emerging class of organophosphorus reagent K. Michal Pietrusiewicz,
Marek Stankevič ··················································································································································25
O-15 Synthesis of new functionalized phosphorus substituted derivatives of 2,6-di-tert-butyl-4methylphenol
A.A. Prishchenko, M.V. Livantsov, O.P. Novikova, L.I. Livantsova, E.R. Milaeva·························26
O-16 Microbial desymmetrization of racemic mixture of (1-hydroxyphenylmethyl)phenylphosphinate
ethyl ester via oxidation of one optical isomer Magdalena Klimek-Ochab, Ewa Żymańczyk-Duda,
Małgorzata Brzezińska-Rodak, Paweł Kafarski and Barbara Lejczak······································································27
O-18 Guanidinophosphazenes: design and synthesis of a novel family of uncharged organic super
bases Alexander A. Kolomeitsev, Ilmar A. Koppel, Toomas Rodima, Jan Barten, Enno Lork,
Gerd-Volker Röschenthaler, Ivari Kaljurand, Agnes Kütt, Ivar Koppel, Vahur Mäemets, Ivo Leito····························28
O-19 Preparation and characterization of novel room temperature ionic liquids based on quaternary
phosphonium cations on quaternary phosphonium cations Katsuhiko Tsunashima, Masashi Sugiya ···29
O-20 Investigating the michaelis-becker reaction in phosphonium and imidazolium ionic liquids
Laura K. Byington Congiardo, Ahn Vu, Erika Shaffer, W. David Stegbauer, Robert Hartsock, D. Andrew Knight···30
O-21 A new useful synthetic pathway to trifluoromethyl phosphates O. A. Shyshkov, A.A. Kolomeitsev
G.-V. Röschenthaler·············································································································································31
O-22 New methods, and strategies for asymmetric synthesis of organophosphorus compounds
Kolodiazhnyi O.I., Guliayko, I.V, Gryshkun E.V., Kolodiazhna, A.O., Nesterov V.V., Kachkovskyi G. O. ···················32
O-23 Imidoyl chlorides: new promising building blocks in synthesis of α-aminophosphoryl compounds
P. P. Onys’ko, Yu. V. Rassukana, A. A. Sinitsa·······································································································33
O-24 Kinetics and mechanism of the oxidation of lower oxyacids of phosphorus by morpholinium
chlorochromate Pradeep K. Sharma············································································································34
O-25 Functionalized phosphoryl compounds: synthesis, extraction, transport and ionophore
properties R.A. Cherkasov, A.R. Garifzjanov, N.S. Krasnova, A.S. Talan, L.A. Burnaeva, G.A. Ivkova·······35
O-26 Investigating the synthetic potential of aminoalkylferrocenyldichlorophosphanes S. Tschirschwitz,
P. Lönnecke, E. Hey-Hawkins·······························································································································36
O-27 Synthesis and redox properties of crowded diphosphines: approaches toward
phosphorus-phosphorus inter-valence charge transfer systems Shigeru Sasaki, Masatoshi Izawa,
Kohji Sasaki, Kiyotoshi Kato, Midori Murakami, Fumiki Murakami, Masaaki Yoshifuji, Noboru Morita ···················37
II

O-28 The organophosphorus sulfenyl bromides as versatile reagents for cysteine derivatives
functionalization by unsymmetrical disulfide bond formation Mateusz Szymelfejnik,
Sebastian Demkowicz, Dariusz Witt, and Janusz Rachon························································································38
O-29 Ambident electrophilicity of 5-membered ring phosphate triesters Nissan Ashkenazi,
Yoffi Segall, Yishai Karton, Sanjio S. Zade, Michael Bendikov················································································39
O-30 A new approach to the synthesis of phosphoranes on the basis of the reaction of
benzo[d]-1,3,2-dioxaphospholes, having β- or γ-unsaturated group in substituent, with
compounds containing multiple bonds V.F.Mironov, L.M.Burnaeva, L.M.Abdrakhmanova,
M.N.Dimukhametov, Yu.yu. Kotorova, I.V.Konovalova···························································································40
O-31 Diastereoselective synthesis of enantiopure α-aminophosphonic acids derivatives Vladimir A. Alfonsov ·······41
O-32 Phosphorylation of imino analogs of α-halocarbonyl compounds Yuliya V. Rassukana,
Petro P. Onys’ko, Anatoly D. Sinitsa·····················································································································42
O-105 Highly stereoselective and stereospecific epoxidation of 2-phospholenes and N-glycosides of
phospha sugars and their bioassays Mitsuji Yamashita, Taishi Niimi, Michio Fujie,
Valluru Krishna Reddy, Hirono Totsuka, Buchammagari Haritha, Maddali Kasthuraiah Reddy, Satoki Nakamura,
Kazuhide Asai, Takuya Suyama, Gang Yu, Masaki Takahashi, and Tatsuo Oshikawa ···············································43
O-106 Chiral P-heterocycles: efficient method for the optical resolution of 3-methyl-3-phospholene
1-oxides Tibor Novák, József Schindler, Viktória Ujj, János Deme, Ádám Bódis, Elemér Fogassy,
György Keglevich ················································································································································44
O-107 Air-stable chiral primary phosphines L. J. Higham, R. M. Hiney , D. G. Gilheany ································45
P-1 α-iminotrifluoroethyl phosphonate – the first representative of C-phosphorylated N-H imines
A. D. Sinitsa, M. V. Kolotylo, Yu. V. Rassukana, V.V. Pirozhenko, P. P. Onys’ko,·················································46
P-2 Synthesis of calix[4]resorcins, containing phosphoryl fragments on the bottom rim of the
molecule A. R. Burilov, I. R. Kniazeva, Yu. M. Sadykova, M. A. Pudovik, W.D. Habicher, I. Baier,
A. I. Konovalov····················································································································································47
P-4 Interaction of 3-alkyl-2-alkoxy-1,3,2-oxazaphosphinanes with alkylchloroformates A.E. Shipov,
G.K. Genkina, P.V. Petrovskii, T.A. Mastryukova···································································································48
P-6 2,2,2-tribromonaphtho[2,3-d]-1,3,2-dioxaphosphole: obtaining and reaction with phenylacetylene
A.V.Bogdanov, V.F.Мironov, B.I.Buzykin, A.B.Dobrynin, D.B.Krivolapov, А.I.Konovalov········································49
P-7 Synthesis, characterization and applications of novel iminophosphinites Jake Yorke,
Sarah K. D. Beaton, Aibing Xia ····························································································································50
P-9 Synthesis and reactions of phosphaisocoumarins Ai-Yun Peng, Bo Wang, Xun Yang···························51
P-14 Nucleophilic phosphine-catalyzed [3+2] cycloaddition of allenes with N-(thio)phosphoryl imines:
facile synthesis of substituted 3-pyrrolines Bo Zhang, Zhengjie He························································52
P-17 Diselenophosphates: synthesis, reaction with electrophiles, and P-Se bond cleavage Chen-Wei Liu ···53
P-23 Tricycles synthesized by the reaction of PCl5 with open-chained molecules Ferdinand Belaj·······54
P-24 Monodentate spiro phosphonites: highly efficient ligands for asymmetric hydrogenation of
non-acylated enamines Guo-Hua Hou, Shou-Fei Zhu, Jian-Hua Xie, Qi-Lin Zhou···································55
P-25 Microwave-assisted synthesis in organophosphorus chemistry György Keglevich, Melinda Sipos,
Anna Szekrényi, Eszter Dudás, Daniella Takács and Emília Hohmann ·································································56
P-30 Synthesis and properties of pentacoordinate phosphorus compounds containing a pentacoodinate
silicon atom Hideaki Miyake, Naokazu Kano, and Takayuki Kawashima·······················································57
III

P-31 Synthesis of a novel apical–equatorial–equatorial type tridentate ligand and construction of
pentacoordinate phosphorus compounds Hideaki Yamamichi, Shiro Matsukawa, Yohsuke Yamamoto···58
P-34 The catalytic ring-closure reaction in the presence of phosphorous oxychloride Hui Wang,
Renzhong Qiao····················································································································································59
P-35 Dithiophosphorylation of cyclic monoterpenes Il’yas S. Nizamov , Artiem V. Sofronov,
Rafael A. Cherkasov, Liliya E. Nikitina ·················································································································60
P-36 Backgrounds for the technology for the preparation of organophosphorous precursors
Magdeev I.M., Budnikova Yu.H., Muslinkin A.A., Nabiullin V.N., Berdnik I.V. ·························································61
P-37 Synthesis of 1,2-azaphosphetidines with amino acid fragment Inga M.Aladzheva,
Olga V.Bykhovskaya, Pavel V.Petrovskii, Tatyana A.Mastryukova ··········································································62
P-38 Asymmetric syntheses of new phosphonotaxoids Irina V. Guliaiko, Oleg I. Kolodiazhnyi························63
P-42 X-ray crystal structure of hydrolysates of triphenylphosphine dichloride Jian Chen Zhang,
Wen Ping Shi, Jun Xu, Yu Fen Zhao······················································································································64
P-46 The synthesis of 7,11,18,21-tetraoxa-1,3,5,13,15,17-hexaaza-2,4,6λ5,12λ5, 14,16-hexaphospha
trispiro[5.2.2.5.2.2]heneicosa-1,3,5,12,14,16-hexaene Ju Zhiyu, Zou Ruyi, Yin Zhengming, Ye Yong,
Liao Xincheng, Zhao Yufen···································································································································66
P-47 P-nitrophenoxycarbonylphosphonate diesters-potent reagents for the synthesis of hindered
carbamoylphosphonates Julia Frant, Irena Beylis, Naama Mussai, Reuven Reich and Eli Breuer··················67
P-48 Phosphorylation of dihydroxy anthraquinones by Atherton-Todd reaction Jun-Feng Zhao,
Xian-Li Wu, Si-Xing Zhang, Xin-Cheng Liao, Shu-Xia Cao, Yan-Chun Guo, Yu-Fen Zhao ······································68
P-49 Decomposition reaction of tetra-hydroxymethylphosphonium chloride Kaiqi Shi, Ya Li,
Lan Jiang, Qiaoyun Ye, Shuangxi Shao············································································································69
P-50 Phosphonilation of 1,3-diaryl-2,3-dihydro-1H-naphth[1,2-е][1,3]oxazine by dialkyl and diaryl
phosphonates Kirill E. Metlushka, Vladimir A. Alfonsov, Charles E. McKenna, Boris A. Kashemirov,
Olga N. Kataeva, Viktor F. Zheltukhin, Dilyara N. Sadkova, Alexey B. Dobrynin·····················································70
P-51 Dimenthyl (2R)-2-hydroxy-3-chloropropylphosphonate – accessible chiron for the asymmetric
synthesis of hydroxyphosphonates Kolodiazhnyi O.I., Nesterov V.V. ·····················································71
P-55 Synthesis n-phosphorylated chrysin-7-yl amino acid esters Li Wenfeng, Chen Xiaolan, Yuan Jinwei,
Qu Lingbo, Zhao Yufen ········································································································································72
P-57 Applications of Lawasson’s reagent in synthesis of biologically active phopshorus-heterocycles
Liang-Nian He, Jin-Quan Wang, Ya Du, Fei Cai ···································································································73
P-62 Phosphorous acid nucleophilic addition at carbonyl groups Li-Ping Zhanga , LingBo Qu,
Yu-Fen Zhao ·······················································································································································74
P-64 The synthesis of tetracyclic phosphorate M.A.Pudovik, L.K.Kibardina, S.A.Terent’eva, O.N.Kataeva,
G.A.Chmutova, V.A.Alfonsov································································································································75
P-65 Abnormal reactivity of arylaminomethylenebisphosphonates. aminomethylation on benzene ring
in base medium M.O.Lozinsky, A.L.Chuiko ·······································································································76
P-69 The preparation of nitrogen-containing heteroaryoylphosphonates and their reactions with
trialkyl phosphites D. Vaughan Griffiths, Michael C. Salt and Helen V. Taylor············································77
P-71 Reaction of racemic and non-racemic silylated (1-phenyl)ethylamine with O-phenylchloromethyl
isothiocyanatothiophosphonate. Synthesis of optically active 1,3,4-thiazaphosphole Ludmila K.
Kibardina, Mikhail A. Pudovik, Natalia A. Khailova, Vladimir A. Alfonsov, Olga N. Kataeva···································78
IV

P-73 Study of reaction of acetylenic phosphonates with carbanionic nucleophiles N.G. Didkovskii,
A.I Petryanina, A.V. Dogadina, N.I. Svintsitskaya and B.I. Ionin·············································································79
P-75 The phospho-aldol reaction and complexes of aluminium containing salcyan and related ligands
Nichola E. Cosgrove, Terence P. Kee····················································································································80
P-78 Synthesis of 2-substitued-pyrano[2,3-d]pyrimidin-4(3H)-one derivatives using iminophosphorane
Qing-Yun Ren, Hong-Wu He·································································································································81
P-81 Synthesis of solanesyl phosphonate Qu Lingbo, Shi Xiaona, Chen Xiaolan ················································82
P-86 Synthesys and structural peculiarities of phosphorus pentachloride complexes with
4-dimethylaminopyridine and N-methylimidazole S.E.Pipko, L.V.Bezgubenko, A.D.Sinitsa,
E.G.Kapustin, E.B.Rusanov, M.I.Povolotskii··········································································································83
P-87 Chemistry of fulvene-type P-heterocyclic compounds Shigekazu Ito, Hideaki Miyake, Satoshi
Sekiguchi, Matthias Freytag, Masaaki Yoshifuji·····································································································84
P-89 Synthesis and complexations of a novel stable carbene bearing a phosphorus ylide Shin-ya Nakafuji,
Junji Kobayashi, and Takayuki Kawashima···········································································································85
P-91 An efficient synthesis of α-(substituted phenoxy acetoxy)alkyl phosphinates sodium salts Tao Wang,
Hong Wu He························································································································································86
P-93 Phosphorylacetic acid thioamides as key substancesfor phosphorylated heterocycles V.A. Kozlov,
I. L. Odinets, D.V. Aleksanyan, P.V. Petrovskii, T. A. Mastryukova ·········································································87
P-94 The formation of ion-radical salts in the reaction of fullerene C60 with Phosphorus (III) amides
I.P.Romanova, V.F.Mironov, G.G.Yusupova, О.А.Larionova, V.I.Morozov, O.G.Sinyashin·······································88
P-95 New method for the asymmetric reduction of ketophosphonates Vitaly V. Nesterov,
Oleg I. Kolodiazhnyi············································································································································89
P-96 Diastereoselective synthesis of enantiopure cyclic α- aminophosphonic acids Vladimir A. Alfonsov,
Charles E. McKenna, Еvgenia V. Bayandina, Boris Kashemirov, Liliya N. Yarmieva, Olga N.Kataeva, Lyudmila
N.Punegova·························································································································································90
P-100 Studies on the synthesis and separation of isoleucine oligopeptides assisted by phosphorus
oxychloride Wei-Na CAO,Li-Na TANG,Li MA,Kui LU,Yu-Fen ZHAO················································91
P-101 Synthesis of bis(phosphonates) pyrrolidines derivatives Feng Gao, Ting-ting Wang,
Ying-jun Song, Wen-hu Wang ·······························································································································92
P-104 Synthesis of novel bicycli caged phosphate derivatives Wen-Yan MO, Hong-Wu HE···························93
P-106 The synthesis and reactions of alkyl 2,3,3-tris(dialkoxyphosphoryl)propionates and alkyl
2,3,3-tris(dialkoxyphosphoryl)acrylates Yuen-Ki Cheong, Philip Duncanson, D. Vaughan Griffiths,
Xiao Han ····························································································································································94
P-112 Reactions between N-(thio)phosphoryl imines and diethylzinc Xinpeng Ma, Xinyuan Xu,
Chungui Wang, Guofeng Zhao, Zhenghong Zhou, Chuchi Tang ··············································································95
P-113 Aza-henry reaction between N-thiophosphoryl imines and nitromethane Xinpeng Ma,
Xinyuan Xu, Chungui Wang, Guofeng Zhao, Zhenghong Zhou, Chuchi Tang ···························································96
P-114 Organocatalytic asymmetric synthesis of α- hydroxy phosphonates Xinyong Li, Weiwei Jin,
Caibao Chen, Wen-Jing Xiao································································································································97
P-115 The aza-morita-baylis-hillman reaction of N-thiophosphoryl imines catalyzed by
1,3,5-triaza-7-phosphaadmantane Xinyuan Xu, Chungui Wang, Zhenghong Zhou, Chuchi Tang ···············98
V

P-118 Polarity and conformations of 1,2,4,5-tetra(tert-butylphospha)cyclohexanes in solution Ya.A. Vereshchagina,
E.A. Ishmaeva, D.V. Chachkov, A.A. Gazizova, Z.S. Novikova ················································································99
P-119 Novel ionic phosphine ligands: their synthesis and application in suzuki coupling reaction in
ionic liquid Yan Chen,Guang-Ao Yu,Yong Ren,Xiang-Gao Meng,Jin-Tao Guan,Sheng Hua Liu ······100
P-120 Synthesis and characterization of novel bile acids derived H-phosphonates conjugates Yan Li,
Yong Ju, Yufen Zhao ··········································································································································101
P-121 Study of the reaction between N- (O, O-diisopropyl) phosphoryl amino acids and the mixed
nucleotides Yanchun Guo, Shuxia Cao, Yali Xie, Xianli Wu, Xincheng Liao, Yufen Zhao ······························102
P-127 Organocatalytic friedel-crafts alkylations of indoles with dialkyl Ying-Cen Guo, Dong-Pin Li,
Wen-Jing Xiao···················································································································································103
P-129 Synthesis of L-phenylalanine dipeptide mediated by phosphorus oxychloride and separation by
RPLC Ying-yan Yao,Kui-Lu··················································································································104
P-130 Synthesis of some new 2-(bis-β-chloroethylamin) 7-methoxyl-3-substitutedphenyl-4-methyl-1, 3,
2-benzoxazaphosphorin 2-oxides Yuan Jinwei, Chen Xiaolan, Qu Lingbo, Yufen Zhao,·························106
P-132 The reaction of pyrrole-2,5-diones and their halogenated derivatives with trivalent phosphorus
compounds Yuen-Ki Cheong, Philip Duncanson, D. Vaughan Griffiths························································107
P-134 Synthesis of diphenyl α-(O-phenyl bis(2-chloroethyl)amidophosphorylamino)phosphonates
Zhanwei Cui, Zhiwei Miao, Jianfeng Zhang, Ruyu Chen·······················································································108
P-138 Modified alkaloids as organocatalysts for the asymmetric synthesis of organophosphorus
compounds A.O. Kolodiazhnaya, V.P.Kukhar, O.I. Kolodiazhnyi······························································110
P-144 Reactions of aminoacetylenephosphonates with N-nucleophilic reagents Anastasia V. Aleksandrova,
Alla V. Dogadina, and Boris I. Ionin···················································································································111
P-154 Template-directed synthesis of phosphorous containing macrocycles:structure
P-159
/reactivity-relationships S. Bozkurt, S. Ekici, D. Jaspers, M. Nieger, E. Niecke·······································112
Synthesis and structure of thiophene, selenophene, and related compounds carrying four
phosphoryl groups Shigeru Sasaki, Kazutaka Adachi, Masaaki Yoshifuji, Noboru Morita···························113
P-164 Synthesis of new β-amino-derivatives of alkenylphosphonates R.A.Cherkasov, N.G.Khusainova,
O.A.Mostovaya, E.A.Berdnikov, S.M.Rybakov······································································································114
P-171 Green synthesis of phosphoramides by trimetaphosphate(P3m) NI, F.; Fu, C.; Sun, S. T.; Zhao, Y. F··116
P-175 Phosphinoglycines and phosphinoglycolates J. Heinicke, J. Lach, N. Peulecke, P. G. Jones, I. Dix······117
P-178 Stereospecific preparation of P-chirogenic phosphide boranes from the corresponding
chlorophosphines H. Lauréano, G. Morata, M.L. Auclair, J.C. Henry, P. Richard, C. Darcel, S. Jugé ·······118
P-179 Recent progresses on P-chirogenic phosphine synthesis M. L. Auclair, G. Morata, M. Gomès,
S. Loutsenko, J. C. Henry, P. Richard, C. Darcel, S. Jugé·············································································119
P-186 Synthesis of hexaisopropyltriamidephosphite: Myth or reality? Anatoliy P. Marchenko,
Georgyi N. Koidan, Yurii M. Pustovit , Mark I. Povolotskii, Aleksandr N. Chernega, Aleksandr M.Pinchuk·············120
P-187 A convenient method for the synthesis of cyclophosphamide analogues Zhang Liuji,
Qu Lingbo, Zhang Baojun, Zhao Yufen················································································································121
P-188 Convenient synthesis of α-hydroxyphosphinate Tao Ji, Guo Tang , Hua Fang, Yufen Zhao ···············122
P-190 Synthesis of N-(diisopropyloxyphosphoryl)dipeptides in a one-pot method Kan Lin,
Xiantong Huang, Guo Tang, Yufen Zhao ·············································································································123
VI

P-191 Organicphosphorus compounds as small molecular catalysts in the direct asymmetric aldol
reaction Qin Tao, Guo Tang, Yu-Fen Zhao·······························································································124
Symposium 2
PHOSPHORUS COORDINATION COMPOUNDS AND THEIR USE AS CATALYSTS
KL-5 Design and synthsis of spiro phosphorus ligands for asymmetric catalysis Qi-Lin Zhou················125
KL-6 Synthesis and application of new p-chiral phosphine ligands Tsuneo Imamoto ······························126
KL-15 My excursion to the chemistry of stable diradicals: diphosphetanediyles Edgar Niecke ················127
KL-17 Innovative chiral phosphorines for hydrogenation and hydroformylation Xumu Zhang················128
KL-30 Phosphorus ligands design for coordination chemistry and catalysis P.L. Floch····························129
IL-8 Ambiphilic phosphine/borane derivatives: synthesis and coordination properties S. Bontemps,
G. Bouhadir, K. Miqueu, L. Maron, D. Bourissou ································································································130
IL-11 Synthesis and asymmetric catalysis of new chiral tetradentate aminophosphine ligands
Yan-Yun Li, Zhen-Rong Dong, Wei-Yi Shen, Gui Chen, Xue-Qing Zhang, Hui Zhang , Jingxing Gao·······················131
IL-13 Phosphorus chemistry & sustainable development Pascal Metivier ··················································133
IL-14 Phosphine and phosphine-mimic complexes in catalysis T. S. Andy Hor·······································134
IL-40 Synthesis and chemistry of metallabenzyne Tingbin Wen, Guochen Jia···············································135
O-35 Synthesis of strained-ring phosphorus heterocycles from phosphatriafulvenes and
phosphaheptafulvenes Heydt, H. Bergsträber, U. Hofmann, M.A. Werner, S. Regitz, M·························136
O-36 Highly functionalised phosphorus ligands: synthesis and diverse coordination chemistry Martin B. Smith··137
O-37 P* chiral aminophosphine complexes of Copper (I): Synthesis and X-ray structural characterization
T. Arun Luiz , Babu Varghese, M. N. Sudheendra Rao··························································································138
O-38 Phosphorus trivalent reagents: efficient tools for multicomponent and organocatalytic reactions
David Virieux, Anne Françoise Guillouzic, Henri-Jean Cristau, Jean-Luc Pirat ····················································139
O-39 Bisdithiophosphonic acids in metal complex formation reactions Il’yas S. Nizamov,
Yevgeniy M. Martiyanov, Il’nar D. Nizamov, Alfiya N. Gataulina, Rafael A. Cherkasov ·········································140
O-40 Synthesis and biological evaluation of a highly reaction Zn(II) mononuclear complex for
phosphodiester cleavage Chao Li, Ren-Zhong Qiao, Yu-Fen Zhao·························································141
O-41 Complexes of crown-containing N-phosphorylthioureas with Ni(II) cation F. D. Sokolov,
S. V. Baranov, N. G. Zabirov, R. A. Cherkasov·····································································································142
O-42 Novel heterocyclic p-ligands: synthesis and application in Pt(II) complexes György Keglevich,
Andrea Kerényi, Melinda Sipos, Annamária Balassa, Beatrix Mayer, Tamás Körtvélyesi·····································143
O-43 DoM chemistry of phosphinic amides: synthesis of ligands and their application in robust high
performance catalysts D. Bradley G. Williams······················································································144
O-109 Design, synthesis, and application of phosphaalkenes to unique palladium and gold catalysts
Shigekazu Ito, Matthias Freytag, Hongze Liang, Katsunori Nishide, Masaaki Yoshifuji ··········································145
P-18 Novel 36- and 38-membered P,N-containing cyclophanes with large hydrophobic cavities
D.V.Kulikov, A.S.Balueva, A.A.Karasik, A.V.Kozlov, Sh.K.Latypov, O.N.Kataeva, P.Lönnecke, E.Hey-Hawkins,
O.G.Sinyashin ···················································································································································146
P-20 Phosphorus functionalised carbenes: synthesis and coordination properties D.Morvan, J.J.Yaouanc,
P.A.Jaffrès, J.F.Capon, P.Schollhammer, J.Talarmin, F.Gloaguen.·······································································148
VII

P-22 Extraction properties of 1,10-da-18-crown-6, modified by exocyclyc chelating groups Felix D. Sokolov,
Maria G. Babashkina, Damir A. Safin, Nail G. Zabirov, Rafael A. Cherkasov ·····················································149
P-26 Chiral spiro monophosphites for Rh-catalyzed asymmetric addition of arylboronic acids to
aldehydes, ketones and imines Hai-Feng Duan, Shou-Fei Zhu, Yi-Xia Jia, Qi-Lin Zhou···························150
P-59 Synthesis of O,O-dialkyl-2-oxo-2-(4-(selenomor pholinosulfonyl)phenylamino)ethylphosphonate
Fang Wang, Liming Hu, Xiaopeng Li, Xuemei Xu························································································151
P-105 Synthesis of chiral spirobitetraline phosphoramidite ligands Hai-Feng Duan, Shou-Fei Zhu,
Yi-Xia Jia, Qi-Lin Zhou······································································································································152
P-161 Synthesis and mechanism of phosphaisoquinolin-1-ones by Pd(II)-catalyzed cyclization of
O-(1-alkynyl)phenylphosphonamide monoesters Wei Tang, Yi-Xiang Ding········································153
P-174 Novel pyrido- and benzo-annulated 1,3-azaphospholes J. Heinicke, M. S. S. Adam, B. R. Aluri,
P.G. Jones·························································································································································155
P-177 Designing phosphorus ligands at the P-center for asymmetric reactions catalyzed by Rh or Pd
complexes C. Darcel, D. Moulin, C. Bauduin, M. Gomès, J.C. Henry, M. Lagrelette, P. Richard·················156
P-196 N-heterocyclic carbene-Copper complex-catalyzed hydrophosphinylation of alkynes Mingyu Niu, Hua
Fu, Yuyang Jiang, Yufen Zhao ····························································································································157
Symposium 3
STRUCTURE AND REACTIVITY OF INORGANIC PHOSPHORUS COMPOUNDS
KL-11 Biologically relevant phosphoranes: structural characterization of glucofuranose and
xylofuranose phosphoranes as applied to phosphoryl transfer enzymes Robert Holmes,
A. Chandrasekaran, Natalya V. Timosheva··········································································································159
KL-19 Studies on stable 1,3-diphosphacyclobutane-2,4-diyls Masaaki Yoshifuji, Anthony J. Arduengo, III and
Shigekazu Ito·····················································································································································161
IL-31 Organophosphorus Pi-conjugated materials for optoelectronic applications Muriel Hissler,
Christophe Lescop, Régis Réau···························································································································162
IL-32 Recent advances in the chemistry of P,N-heterocycles Streubel, R., Özbolat, A., Helten, H., Perez,
J. M., Nieger M.·················································································································································163
IL-50 Radiation-induced synthesis of polymers on the basis of elemental phosphorus N.P. Tarasova ····164
O-72 Influence of media components on processes of radiation-indused polymerization of white
phosphorus I.M. Artemkina, A.S. Vilesov, Y.V. Smetannikov, N.P. Tarasova············································165
O-73 An effective methodology of P,N-macrocycles design A.A. Karasik, A.S. Baluev, R.N. Naumov,
D.V.Kulikov, Yu.S.Spiridonova, O.G.Sinyashin, E. Hey-Hawkins ··········································································166
O-74 The mechanism of the reaction of alkali metal phenoxides with hexahalocyclotriphosphazenes
Christopher W. Allen, Michael Calichman, Amy Freund·······················································································167
O-75 Strained P2C and P2C2 cyclic cations from phosphaalkenes Derek P. Gates ································168
O-76 New reagents for halogenation of phosphorus Rikard Wärme, Lars Juhlin··········································169
O-79 Bimetallic activation of white phosphorus Dmitry Yakhvarov, Maurizio Peruzzini, Maria Caporali,
Pierluigi Barbaro, Luca Gonsalvi, Stefano Midollini, Annabella Orlandini, Fabrizio Zanobini,Yulia Ganushevich,
Oleg Sinyashin ··················································································································································170
VIII

O-80 Environmentally being chemical conversion of CO2 into organic carbonates catalyzed by
phosphinium salts J.S.Tian, C.X.Miao, J.Q.Wang, F.Cai, Y.Du, Y.Zhao, L.N.He ······································171
O-81 Transition metal complexes containing phosphenium and phosphite ligands: formation and
theoretical approach Hiroshi Nakazawa, Katsuhiko Miyoshi, and Keiko Takano·····································172
O-82 The formation of spherical giant molecules and dynamic behaviour of supramolecular assemblies
based on PN ligand complexes Manfred Scheer, L. J. Gregoriades, R. Merkle, B. P. Johnson, F. Dielmann 173
O-84 The chemical properties of alkali metals heptaphosphides V.А.Miluykov, O.G.Sinyashin,
А.V.Kataev, P.Lonnecke, E.Hey-Hawkins············································································································174
P-10 Designing new metallo-organic catalysts for the asymmetric phospho-aldol reaction Alexandra C. Gledhill,
Tracy D. Nixon, Terence P. Kee··························································································································176
P-15 Electrosynthesis of metal phosphides on the basis of white phosphorus Budnikova Yu.H.,
Krasnov S.A., Gryaznova T.V., Tazeev D.I., Sinyashin O.G.··················································································177
P-76 Novel synthetic routes to phosphorus organic compounds on the basis of the elemental
phosphorus (P4) O. G. Sinyashin, E. S. Batyeva, E.V. Platova, E.K. Badeeva, L.I. Kursheva······················178
P-99 Reaction of 2-R-benzo[d]-1,3,2-oxazaphosphorin-6-ones with hexafluoroacetone V.F.Mironov,
Yu.Yu.Borisova, L.M.Burnaeva, A.T.Gubaidullin, I.A.Litvinov, G.A.Ivkova, N.K.Amerkhanova, I.V.Konovalova ······179
P-117 Study on structure and properties of amorphous Ni-Cu-P alloy coatings prepared by electroless
plating Xu Ruidong, Wang Junli,Guo Zhongcheng ························································································180
P-139 Determination of dexamethasone sodium phosphate in medicament by fluorescence probe of
Symposium 4
Tb 3+ -Tiron complex Chaobiao Huanga, Zhenrong Yu, Libin Zhou······························································181
NUCLEOTIDES AND OLIGONUCLEOTIDES-FROM BASIC TO MEDICINAL
APPLICATIONS; BIOLOGICAL ASPECTS OF PHOSPHORUS CHEMISTRY
KL-14 The chemical biology of histidine triad nucleoside binding proteins Carston R. Wagner···················183
KL-16 Studies on modified oligonucleotides Lihe Zhang·················································································184
KL-21 Kinase and kinase inhibitor as anticancer therapeutics Chen Li ························································185
KL-40 Stereochemistry of enzyme-assisted P-N bond cleavage in adenosine 5'-phosphoramidates and
–phosphoramidothioates Agnieszka Krakowiak, Renata Kaczmarek, Janina Baraniak,
Michał Wieczorek, Wojciech J. Stec ····················································································································186
KL-42 Polyphosphates for drug and gene delivery Renxi Zhuo, Shiwen Huang ··········································187
KL-46 Synthesis and biochemical activity of new oligonucleotide analogs Marvin H. Caruthers ················188
IL-41 Study of artificially selected biocatalysts covalently modified by organophosphorus compounds
Alexander G. Gabibov, Andrey V. Reshetnyak, Maria Francesca Armentano, Natalia A. Ponomarenko, Oxana
Durova, Rustam Ziganshin, Marina Serebryakova, Vadim Govorun, Gennady Gololobov, Herbert C. Morse III,
Alain Friboulet, Sudesh P. Makker, Alfonso Tramontano······················································································189
IL-42 Thermosensitive phosphate/thiophosphate protecting groups and the development of thermolytic
oligonucleotide prodrugs Andrzej Grajkowski, Cristina Ausín, Serge L. Beaucage··································190
IL-43 Advancing biomedical research by development of fluorescent oligonucleotide-based assays
Gerald Zon························································································································································192
IL-44 Non watson-crick structure recognition and its applications Zhen Xi··············································193
IX

IL-45 Probing mechanisms of phosphotransferases with thio effects Karol Bruzik ···································194
IL-47 RNA interference: the new paradigm of drug discovery based on nature's phosphorous
chemistry Muthiah Manoharan·················································································································195
IL-49 Synthesis and biological studies of G-quadruplex stabilizers Lige Ren, Jing Huang, Boqiao Fu,
Xiang Zhou ·······················································································································································196
O-96 Perifosine inhibits multiple signaling pathways in glial progenitors and cooperates with
temozolomide to arrest cell proliferation in gliomas in vivo. Alan H. Shih, Hiro Momota,
Edward Nerio, Eric C Holland ···························································································································197
O-97 A low-molecular phosphinic inhibitor of leucine aminopeptidase of potential medical significance
A.Mucha ···························································································································································198
O-98 Mapping of the functional phosphate groups in the catalytic core of deoxyribozyme 10-23
Barbara Nawrot, Kinga Widera, Marzena Wojcik, Beata Rebowska, Wieslawa Goss, Wojciech J. Stec····················199
O-100 The aza-α-aminophosphonate macrocycles as potential supramolcular hosts for metal ions and
biologically important molecules P.Mlynarz, A.Rydzewska, S.Sliwinska, G.Schroeder,P.Kafarski············200
O-101 Studies on the condensation of H-phosphonate monoesters with S-nucleophiles Renata Hiresova ,
Jacek Stawinski ·················································································································································201
O-103 ESI investigation of non –covalent complexes between phosphorylated daidzein and insulin Chen Xiaolan,
Shi Xiaona, Yuan Jinwei, Lu Jiansha, Qu Lingbo, Zhao Yufen ··············································································202
O-104 Synthesis of novel steroidal bioconjugates with azt and phosphorus Peiyuan Jin, Kai Liu, Yong Ju,
Yufen Zhao························································································································································203
P-33 The chemical synthesis of oligonucleotide phosphoramidates HongYu Zhang, ChunJian Duan,
XiangQian Liu, XiaoLan Chen, LingBo Qu, YuFen Zhao······················································································204
P-41 Studies on the self-assembly of L-serine into L-Serine phosphopeptide mediated by phosphorus
oxychloride Jianchen Zhang, Wenping Shi, Jun Xu, Yufen Zhao·········································································205
P-43 Synthesis of N-protected O-hydroxyl-phenyl - α-aminophosphonic monoester Jianfeng Zhang,
Zhiwei Miao, Zhanwei Cui and Ruyu Chen··········································································································206
P-44 A novel mechanism about the cleavge of N-glycosidic bond in electrospray ionization tandem
mass spectra of nucleotide Jihong Liu, Shuxiao Cao, Ruyi Zou, Jiansha Lu, Xincheng Liao, Yufen Zhao····207
P-45 Synthesis of isoprenoid olefin isomers via phosphonium and phosphoryl stabilized carbanions
José S. Yu, David F. Wiemer·······························································································································208
P-52 Investigation on interaction of L-methionine dipeptide with ct-DNA by ultraviolet spectroscopy
method Kui Lu,Rui Li,Li Ma,Yufen Zhao························································································209
P-61 Remineralization effects of honeysuckle flower solution on initial enamel carious lesions in vitro
Linglin Zhang····················································································································································211
P-72 Self-assembly of L-glutamine into oligo-peptides mediated by phosphroric chloride Li Ma,
Ming-xiu Lü, Wei-na Cao, Kui Lu ·······················································································································212
P-74 Synthesis and biological activity of α-hydroxyphosphonates Na Zuo, Hong-Wu He························213
P-85 Bio-relevant derivatives of calixarene phosphonic acids S.Cherenok, A.Vovk, I.Muravyova,
A.Marcinowicz, J.Poznanski, O. Muzychka, V.Kukhar, W.Zielenkiewicz, V.Kalchenko············································214
P-123 Effects of phosphorylation on the conformation of peptide and protein Yan-Mei Li, Yu-Fen Zhao ···215
P-124 Synthesis and purification of L-hydroxyproline oligo-peptides assisted by phosphorus
oxychloride Yan-ting Sun, Ye-zhen Feng, Kui Lu ·······················································································216
X

P-125 Self-assembly of L-glutamine into oligo-peptides mediated by phosphroric chloride Li Ma,
Ming-xiu Lü, Wei-na Cao, Kui Lu ·······················································································································217
P-135 Design and synthesis of 5’-fluorescently labeled nucleosides Zheng Jinyun, Zhang Shufeng, Zhao Yufen········218
P-140 Microwave-assisted syntheses of 2',3'-o-isopropylidene ribonucleoside 5'-monophosphates Z. Wang,
Y.F. Zhao ··························································································································································219
P-141 The correlation between the estimated partition coefficient P and capacity factor K of amino
acids and phosphoryl amino acids Hongxia Liu, Canfang Zhao, Mian Liu, Yuyang Jiang, Yufen Zhao·····221
P-148 Synthesis of α, β-difluoromethylenebisphosphonate analogs of dntps: probes for DNA
polymerase β Thomas G. Upton1, Boris A. Kashemirov, Charles E. McKenna, Myron F. Goodman, G. K.
Surya Prakash, Roman Kultyshev, Vinod K. Batra, David D. Shock, Lars C. Pedersen, William A. Beard, Samuel
H. Wilson··························································································································································222
O-167 Synthesis of bicyclic furopyrimidine deoxynucleosides conjugated with N-diisopropylphosphoryl
amino acids Qiang XiaoA, Xuanye Jin, Weihong Xiao, Yong Ju··································································223
P-168 Effects of chrysin and its tetraethyl bis-phosphoric ester in the cell cycle and P 21/WAF1 proteins of the human
cervical carcinoma cell line hela Ting Zhang, Xiaolan Chen, Lingbo Qu, Manji Sun, Yufen Zhao·················224
P-170 The peptide bond formation reaction with peptides and proteins in aqueous solution by
inducement of N-phosphoryl α-amino acids Jia Ning Wang, Yan Liu, Dacheng He , Yu-Fen Zhao ··········225
P-172 The synthesis and resolution of the opticle active derivatives of N-thiophosphoramidate
derivatives Anfu Hu, Peng Liu , Pengxiang Xu ,Yufen Zhao ········································································227
P-176 New β-ferrocenyl phosphino α-aminoacids as modular electrochemical biomarker for
CSF114(glyco)peptides A. Colson, J. Bayardon, E. Rémond, F. Nuti, R. Meunier-Prest, M. Kubicky,
C. Darcel, A.M. Papini, S. Jugé ··························································································································228
P-183 A study on the nucleoside analogs using electrospray ionization mass spectrometry Liu Ruoyu,
Ye Yong, Cao Shuxia, Liao Xincheng , Zhao Yufen·······························································································229
P-184 Studies on the noncovalent bonding between ATP and α-aminophosphonic acids derivatives by
ESI-MS and molecular modeling Liu Xiaoxia, Fang Hua, Liu Yan, Zhao Yufen······································230
P-185 Peptide bond formation on C-terminal of peptides in organic solution by inducement of
N-phosphoryl amino acid Liu Xiaoxia, Liu Yan, Zhao Yufen ·································································231
P-193 Synthesis of O-nucleoside N-phosphoryl amino acid methyl ester Chen Wei-Zhu, Gao Yu-Xing,
Li Gang, Zhao Yu-Fen ·······································································································································232
P-195 Protein phosphorylation regulates protein local structure and function Jia Hu, Yu-Fen Zhao, Yan-Mei Li··233
P-196 A fast way to synthesis nucleoside H-phosphonate derivatives Jian-Bin Wu, Jian-Nan Guo, Jun Zhang,
Shu-Na Luo, Xiang Gao, Yu-Fen Zhao ················································································································233
Symposium 5
THEORETICAL ASPECTS OF PHOSPHORUS CHEMISTRY ;
31 P NMR IN BIOLOGICAL SYSTEMS
KL-7 Molecular simulation studies of protein kinases Martin J. Field ························································235
KL-8 From powder NMR tensor to 3D molecular structure, promises or illusion - a 31 P and 13 C case
study on cimitidine Steve C.F. Au-yeung··································································································236
IL-15 NMR investigations of phosphate transfer enzymes Jonathan P. Waltho···········································237
XI

IL-16 Photophysics of DNA and light harvesting systems GuanHua Chen ··················································238
IL-18 QM-MM computation of phosphate transfer by enzymes Charles E. Webster····································239
O-44 1.3-diphosphacyclobutane-diyls as building blocks for extended structures Wolfgang W. Schoeller ··240
O-45 Development of a bidentate ligand based on decafluoro-3-phenyl-3-pentanol: steric effect of
pentafluoroethyl groups on the stereomutation of oequatorial C-apical spirophosphoranes
Y.Yamamoto, X.d.Jiang, K.I.Kakuda, S. Matsukawa, H.Yamamichi ·······································································241
O-46 Conformational analysis of 1,4-heterophosphinanes Ya.A. Vereshchagina, E.A. Ishmaeva,
A.A. Gazizova, D.V. Chachkov, M.G. Voronkov ···································································································242
O-47 Stereoselective synthesis and interconversions of 1,9-diaza-3,7,11,15-tetraphospha
cyclohexadecanes R.N.Naumov, A.A.Karasik, A.V.Kozlov, Sh.K.Latypov, D.B.Krivolapov, A.B.Dobrynin,
I.A.Litvinov, O.N.Kataeva, P.Lönnecke, E.Hey-Hawkins, O.G.Sinyashin ·······························································243
O-48 Reactions of phosphonic acids with bases in aqueous solutions Myund, L. A.; Lu, N; Sidorov, Yu. V.,
Burkov, K. A.·····················································································································································244
O-49 Distinct π bonding capability between phosphinidene and phosphonium ion Hisn-Mei Cheng,
San-Yan Chu ·····················································································································································245
O-50 Dimerization and trimerization of phosphaacetylene. a mechanistic study T. Veszprémi, T. Höltzl,
M.T. Nguyen······················································································································································246
O-52 Bond activation processes in N-heterocyclic phosphines D.Gudat, S.Burck, I.Hajdók, F.Lissner,
M.Nieger···························································································································································247
O-53 Determination of optical purity of aminophosphonates by means of NMR spectroscop E.Rudzińska ·········248
O-54 Phosphorus stabilzes and can be stabilized László Nyulászi······························································249
O-94 Mechanism of amino acids mediated oligomerization into peptides by phosphorus trichloride
W.J.Zhao D.X.Zhao K.Lu ···································································································································250
P-103 Mechanism of amino acids mediated oligomerization into peptides by phosphorus trichloride
Wenjie Zhao, Dongxin Zhao, Kui Lu ···················································································································251
P-137 Can four membered heterophosphete structures exist? “Heterogen” hetero antiaromaticity as a
destabilizing effect Zoltán Mucsi, Tamás Körtvélyesi, Tibor Novák, György Keglevich·······························252
P-155 Synthesis and mechanism studies on amide bond by hexamethylphosphoramide(HMPA)
Jianbo Hou, Tongjian Wang, Kan Lin, Guo Tang, Yufen Zhao ··············································································253
P-163 Interaction of 2H-1,2,3-diazaphosphole with diols M.A.Khusainov, R.A.Cherkasov, N.G.Khusainov ,
O.A.Mostovaya, I.F.Gataulina····························································································································254
P-169 Locating the reaction paths of N-(dialkyloxyphosphoryl) amino acids by Nudged Elastic
Band(NEB) method NI, F.; Zeng, Z. P.; Zhao, Y. F ·················································································255
P-194 The formation mechanism of the α-hydroxyphosphonate: a theoretical study Zeng Zhiping,
Fang Hua, Zhao Yufen ·······································································································································257
P-182
31
P NMR assay of the enantiomeric excess by using quinine as chiral solvating agent Liu Ruoyu,
Ye Yong, Chen Xiaolan , Liao Xincheng, Zhao Yufen····························································································258
XII

Symposium 6
PHOSPHORUS COMPOUND AND MEDICINAL CHEMISTRY
KL-9 A correlation of antiresorptive structure activity relationships in nitrogen-containing
bisphosphonates Co-crystalized in farnesyl diphosphate synthase suggests their binding mode
F. H. Ebetino, B. L. Barnett, B. A. Kashemirov, C. Roze, C. E. McKenna, J. Hogan, A. G. Evdokimov, M. E.
Pokross, J. Dunford, Z. Xia, K. Kavanagh, R. G. G. Russell··················································································259
KL-10 Specificity of phosphothreonine recognition by FHA domains Ming-Daw Tsai ·····························260
KL-18 Phosphonate analogs for drug design Charles E. McKenna ·································································261
KL-20 Chiral functionalized phosphonates with biological significance Chengye Yuan······························262
IL-19 Stereocontrolled synthesis of phsophorothioate DNA and RNA by the oxazaphospholidine
approach Takeshi Wada ···························································································································263
IL-20 3',5'-cyclic diguanylic acid and related compounds: synthesis, chemical properties, and biological
activities Yoshihiro Hayakawa ··················································································································265
IL-23 Synthesis of dinucleoside phosphates from c-di-GMP to AZTppppA Zhaoying Zhang, Qianwei Han,
Jianwei Zhao, Barbara L. Gaffney, Roger A. Jones ······························································································266
IL-24 The effects of revisible phosphorylation on peptide and protein local structure Yan-Mei Li,
Yu-Fen Zhao ·····················································································································································267
IL-25 All phosphates are not born chemically equal in RNA Jyoti Chattopadhyaya··································268
IL-26 Design, synthesis and biological activity of α-amino-substituted thiophosphate-phosphonates and
novel naphthoquinone fused phosphorus heterocycles Zhanwei Cui ,Zhiwei Mia, Jianfeng Zhang,
Ruyu Chen ························································································································································269
IL-27 Recent advances in carbamoylphosphonate based matrix metalloproteinase (MMP) inhibitors.
a class of non-toxic in-vivo active drug candidates Eli Breuer ···························································271
IL-48 Novel functionality in organophosphorus chemistry Koop Lammertsma ···········································272
IL-64 Studying the phosphorylation of flavonoids E. E. Nifantyev, M. P. Koroteev, G. Z. Kaziev, T. Wang,
L. H. Cao ··························································································································································273
O-56 Cationic lipids based on phosphonate & phosphoramidate chemistry: synthesis and application
to gene therapy Paul-Alain Jaffrès, Mathieu Mével, Jean-Jacques Yaouanc, Jean-Claude Clément,
Dominique Cartier, Laure Burel, Philippe Giamarchi, Tristan Montier, Pascal Delépine, Pierre Lehn, Claude
Férec, Chantal Pichon, Patrick Midoux ··············································································································274
O-57 Enantiomeric separation of a novel α-anminophosphonates containing benzothiazol moiety by
liquid chromatography using amylose stationary phase Ping Lu, Baoan Song, Deyu Hu,
Song Yang, Linhong Jin, Wei Xue, Yuping Zhang·································································································275
O-58 BEAD-based approaches to develop thioaptamers for diagnostics and therapeutics Xianbin Yang,
Duane Beasley, Bruce A. Luxon, Johnnie Engelhardt, Mark Shumbera, David G. Gorenstein ·································276
O-59 Design and construction of diagnostic chips for cancers Anna Czernicka and Paweł Kafarski············277
O-62 Factors that may predict clinical potencies of nitrogen-containing bisphosphonates; novel
methods dissociate enzyme- and hydroxyapatite-binding affinities Z.Xia,J.Dunford,
M.A.Lawson, J.T.Triffitt, B.L.Barnett, C.Roze, B.Kashemirov, C.E.McKenna, F.H.Ebetino, R.G.G. Russell ·············278
O-63 Novel organophosphorus inhibitors of glutamine synthetase Łukasz Berlicki, Agnieszka Grabowiecka,
Giuseppe Forlani, Paweł Kafarski ······················································································································279
XIII

O-67 Investigations into the oxidative stability of hydroxymethyl- and bis(hydroxymethyl)phosphines
D. V. Griffiths, H. J. Groombridge ······················································································································280
O-69 Organophosphonate inhibitors of cathepsins Paweł Kafarski···························································281
O-70 Synthesis and dental aspects of 1,3-bis(methacrylamido)propane-2-yl dihydroxyphosphate
F. Zeuner, N. Moszner, J. Angermann ·················································································································282
O-71 New efficient synthesis of 2-substituted benzothieno[3,2-d]pyrimidin-4(3H)-ones via an
iminophosphorane Sheng-Zhen Xu, Yang-Gen Hu, Ming-Wu Ding··························································283
P-3 Calixarene methylenebisphosphonic acids: alkaline phosphatase inhibition and docking studies
A. Vovk, V. Kalchenko, O. Muzychka, V. Tanchuk, I. Muravyov, A. Shivanyuk, S. Cherenok, V. Kukhar···················284
P-5 α-(N-benzylamino)benzylphosphonic acids: stereoselectivity of binding to prostatic acid
phosphatase O.I. Kolodiazhnyi, A.I.Vovk, I.M. Mischenko, S.V. Tanchuk, G.A. Kachkovskyi, S.Yu. Sheiko,
V.P. Kukhar ······················································································································································285
P-11 Geranyl and farnesyl bisphosphonates inhibit protein geranylgeranylation through ggpp
depletion Andrew J. Wiemer, Huaxiang Tong, David F. Wiemer, Raymond J. Hohl. ·····································286
P-39 Preparation of new [1,4,2]-oxazaphosphinanes: potentially antidepressive agent David Virieux,
Jean-Noël Volle, Jean-Luc Pirat ·························································································································287
P-40 Antitumor effect of betaine and its impact on the phosphorylation process of rats bearing S180
Ji Yu-Bin, Zhang Yu-Jin ·····································································································································288
P-54 Synthesis and seperation of L-trytophan oligo-peptides assisted by phosphorus oxychloride
Li Ma, Hai-ping Ren, Kui Lu,Yu-fen Zhao ···········································································································289
P-66 Thioureido derivatives of methylenebisphosphonic acid as potential inhibitors of alkaline
phosphatases M. Lozynsky, A. Vovk, A. Chuiko, L. Kononets, V. Tanchuk, I. Muravyova, V. Kukhar·············290
P-67 Phosphoryl substituted 3,5-bis(arylidene)-4-piperidones posessing high antitumor- activity M.V. Makarov,
I.L. Odinets, O.I. Artyushin,E.Yu. Rybalkina, K.A. Lyssenko, T.V. Timofeeva, M.Yu. Antipina ·································291
P-77 New polyamines phosphoramidate vectors for gene therapy Mathieu Mével, François Lamarche,
Jean-claude Clément, Jean-jacques Yaouanc, Laure Burel, Philippe Giamarchi, Tristan Montier, Pascal Delépine,
Pierre Lehn, Paul-Alain Jaffrès, Claude Férec.····································································································292
P-79 Synthesis and drug release behavior of unsaturated polyphosphoester Qiu Jin-Jun, Bao Rui,
Liu Cheng-Mei ··················································································································································293
P-80 In vitro degradation properties of unsaturated polyphosphoester β-tricalcium phosphate
composites Qiu Jin-Jun, Bao Rui, Liu Cheng-Mei ······················································································294
P-82 The synthesis, acid-basic and membrane-transport properties of the phosphorylated amines
Rafael A. Cherkasov, Airat R.Garifzjanov, Maxim V. Khakimov, Alexey S. Talan, Gul’nara A. Ivkova·····················295
P-102 Identification of self-assembly products of valine mediated by phosphorus trichloride by ESI
mass spcetrometry Wenjie Zhao, Li Ma, Kui Lu, Yufen Zhao ····································································296
P-108 Discovery of alkenylphosphorus compounds as a new class of cytotoxic agents for cancer cells
Xiaohui Wang, Li-Biao Han ·······························································································································297
P-109 The synthsis of tripyrrole peptide containing phosphonyl Li-feng Cao, Li-li Shen, Ru-yi Zou,
Cun-jiang Liu, Yong Ye, Xin-cheng Liao, Yu-fen Zhao··························································································298
P-142 Developing a simple assay to screen for organophosphatases Gareth Williams ································299
P-143 The pharmacokinetics analysis of the phosphoryl peptides in MCF-7/ADR cells Peng Zhang,
Hongxia Liu, Zhenhua Xie ,Feng Liu, Mian Liu ,Yuyang Jiang ·············································································300
XIV

P-145 New phosphoramidate dicationic vectors for gene therapy Mathieu Mével, François Lamarche,
Jean-claude Clément, Jean-jacques Yaouanc, Laure Burel, Philippe Giamarchi, Tristan Montier, Pascal Delépine,
Pierre Lehn, Paul-Alain Jaffrès, Claude Férec ····································································································301
P-146 Novel cidofovir prodrugs: conceptual and synthetic strategies Boris A. Kashemirov, Joy Lynn F. Bala,
Xiaolan Chen, Zhidao Xia, R. Graham G.Russell, Charles E. McKenna ································································302
P-147 Fluorescently labeled risedronate and related analogs: novel synthesis and evaluation as imaging
probes Larryn W. Peterson, Boris A. Kashemirov, John M. Hilfinger, Charles E. McKenna···························303
P-149 Syntheses and characterizations of α-aminophosphonic acids and their derivatives Fang Hua,
Fang Meijuan, Liu Linna, Zhao Yufen·················································································································304
P-150 Ligand-protein inverse docking as a potential tool in the computer search of protein targets of
mycoediketopiperazine, a novel fungal metabolite from a papularia SP. Fang Meijuan, Fang Hua,
Ji Zhiliang, Luo Shun, Zhao Yufen ······················································································································305
P-151 Synthesis of mopholino oligonucleotide with normal phosphate backbone by phosphoramidite
methodology Pu-Qin Cai, Nan Zhang, Chun Guo, Pei-Zhuo Zhang, Yu-Yang Jiang, Yu-Fen Zhao··················307
P-152 Electrospray ionization mass spectra of amino acid methyl ester 5'-phosphoramidates of 2',
3'-isopropylideneuridine Chen Wei-Zhu, Gao Yu-Xing, Zhao Yu-Fen ························································308
P-153 Synthesis and bioactivity of six-ring nucleoside modified siRNA Nan Zhang, Yue Wang, Pu-Qin Cai,
Pei-Zhuo Zhang, Yu-Yang Jiang, Yufen Zhao·······································································································309
P-156 A novel synthesis of o-phosphorylatedn-menthoxy-carbonyl tyrosine Wang Tongjian, Cheng Fang,
Tang Guo, Zhao Yufen ·······································································································································310
P-157 Inhibition of pokemon gene expression by antisense oligonucleotides Nan Zhang, Yue Wang,
Zhen-Hua Xie, Yu-Yang Jiang , Yu-Fen Zhao·······································································································311
P-158 Antisense therapy targeting pokemon oncogene in MCF-7 CEL Lan Zhang, Wen-Peng Li,
Zhen-Hua Xie, Yu-Yang Jiang , Yu-Fen Zhao·······································································································312
P-162 The positive and negative electrospray ionization (ESI) mass spectrometry of
P-197
1-(N-ethoxycarbonylamino) arylmethylphosphonic monoesters Yuan Ma, Wei Liu, Yufen Zhao·········313
The synthesis and biological evaluation of benzamide riboside and its phosphordiamidate
prodrug Jianning Zhou, Nan Zhang, Chunyan Tan, Jian Fan, Chun Guo, Yuyang Jiang ·································313
Symposium 7
PHOSPHORUS CHEMISTRY IN AGRICULTURE, INDUSTRY
AND MATERIALS SCIENCE
KL-12 Overview on op metabolism chemistry and its relationship to biological and toxic actions Philip W. Lee ·····315
IL-33 Food safety: monitoring of organophosphate pesticide residues in crops and food Canping Pan ·····316
IL-34 The role of phosphorus in crop protection: experimental and commercial disease and weed
control agents Roger G. Hall····················································································································317
IL-35 The use of op and development of new organophosphorus agrochemicals in China Hong-wu He ··318
IL-36 Current status of organophosphorus insecticide and stereochemistry Mitsuru Sasaki······················319
IL-37 Global use of organophosphorus pesticides William H. Hendrix, III,···················································320
O-85 “Green” ways of phosphorus compounds preparation Budnikova Yu.H., Krasnov S.A., Graznova T.V.,
Tomilov A.P., Turigin V.V., Magdeev I.M.., Sinyashin O.G. ··················································································321
XV

O-86 Phosphate - an important element in the agricultural and environmental sphere Dirk Freese·······323
O-88 Phosphate removal and recovery with calcined layered double hydroxides as an adsorbent
Liang Lü , Zhaoliang Zhou , Jing He , Yulin Wang , Guoqiang Wu········································································325
O-89 Development, scaleup and commercialisation of catalyst lignds Ranbir Padda and Gordon Docherty 326
O-90 Bleaching chemisty of tris(hydroxymethyl)phosphine and tetrakis(hydroxymethyl)phosphonium
sulfate Thomas Q. Hu , Brian R. James , Richard Chandra , Eric Yu, Dmitry Moiseev···································327
O-91 Use of ion exchange composites based of titanium and zirconium phosphates for cleaning of
water solutions Valery P. Nesterenko·······································································································328
O-92 Selective chromium oligomerisation catalysts with various phosphorus ligands Kevin Blann,
John T. Dixon, Esna Killian, Hulisani Maumela, M., Chris Maumela, Ann E. McConnell, David H. Morgan, Mari
Pretorius, Henriette de Bod, William Gabrielli, Alex Willemse, Pumza Zweni, Palesa Nongodlwana·······················329
O-94 An efficient catalytic asymmetric synthesis and biological evaluation of α-substituted aroyloxyl
phosphonates Hui Liu, Hongwu He, Wen-Jing Xiao ················································································330
O-95 Controlled synthesis of organic-inorganic materials derived from phosphorous compounds.
variable porosity, photoinduced electron-transfer and hydrogen storage Ernesto Brunet,
Olga Juanes, Juan Carlos ··································································································································331
O-108 Study on the preparation of wheat starch phosphate with low degree of substitution Liu Zhongdong,
Yang Yan ··························································································································································333
P-8 Structural characteristic and electrode activities of phosphorus incorporated tetrahedral
amorphous carbon films Aiping Liu, Jiaqi Zhu, Jiecai Han, Huaping Wu·················································334
P-12 Electron conducting materials on the basis of perfluorophenylene-phosphanes Berthold Hoge,
Sonja Hettel, Nina Rehmann·······························································································································335
P-13 Synthesis and cytotoxic evaluation of novel naphthoquinone fused phosphorus heterocycles Bin Wang,
Zhiwei Miao, You Huang, Ruyu Chen, Jie Wang ··································································································336
P-16 1,3,4-oxazodizaole containing cyclo- and polyphosphazene Chen Zhao, Rui Bao, Jin-jun Qiu,
Cheng-mei Liu···················································································································································338
P-19 Stereoselective synthesis and biological activities of O-(E)-1-{1-[(6-chloropyridin-3-yl)methyl]
-5-methyl-1h-1, 2, 3-triazol-4-yl}ethyleneamino O-ethyl O-aryl phosphorothioates De-qing Shi····339
P-27 The influential factor of temperature on synthesis of L-arginine oligo-peptides mediated by
phosphorus oxychloride Haiping Ren , Li Ma , Kui Lu··········································································340
P-28 Distribution and concentration of total nitrogen, total phosphorous and total organic carbon in
South Sea, China Haiyan Wang,Daxiong Han,Jianyun Lin································································341
P-29 Molecular docking of substituted alkylphosphonates to pyruvate dehydrogenase Hao Peng,
Hong-Wu He ·····················································································································································342
P-32 A practical route to synthesis some phosphorylated prodrug Hong-bo Zhang, Ren-Zhong Qiao,
Yufen Zhao························································································································································343
P-53 Ultrasonic photocatalytic degradation of the pesticide “methyl parathion” LI He-ping ··················344
P-56 Application of tetrakis hydroxymethyl phosphonium in leather production Li Ya, Shao Shuangxi,
Jiang Lan, Han Ying, Shi Kaiqi···························································································································345
P-58 The synthesis of N-hydroxymethyl-3-(dialkylphosphono) propionamide Xiao-lian Hu, Ru-yi Zou,
Shang-bin Zhong, Jun-liang Yang, Zhi-yu Ju, Yong Ye, Xin-cheng Liao, Yu-fen Zhao·············································346
XVI

P-60 Electrospray ionization tandem mass spectrometry of N-phosphoryl-α-, β- and γ- amino acids
Liming Qiang, Shuxia Cao, Jianchen Zhang, Xincheng Liao, Yufen Zhao ······························································347
P-63 Sediment phosphorus buffering capacity in drainage ditch in hilly area of purple soil, China
Luo Zhuan-xi1, Zhu Bo,Wang Tao ······················································································································348
P-83 Liquid crystalline behavior of cyclotriphosphazene Rui Bao, Chen Zhao, Jin-jun Qiu, Cheng-mei Liu ··349
P-84 Monitoring influence of reaction conditions on self-assembly into oligo-peptides for three
sulf-amino acids by using ESI-MS Kui Lu,Rui Li,Li Ma ··································································350
P-90 Isolation and determination of diastereoisomers of amino acid hydridophorane by
HPLC-ESI-MS Shuxia Cao, Yali Xie, Jinming Liu, Yanchun Guo, Xincheng Liao, Yufen Zhao ····················351
P-97 Synthesis of long chair organophosphorus compounds on the basis of industrial fractions of
higher olefins Il’yas S. Nizamov, Yan Ye. Popovich, Yevgeniy S. Ermolaev, Il’nar D. Nizamov,
Gulnur G. Sergeenko, Vladimir A. Alfonsov,Elvira S. Batyeva, Magdeev I.M., Reznik V.S., Sinyashin O.G.,
Yarullin R.S.······················································································································································352
P-107 Synthesis and biological activities of O,O-dialkyl 1-((2-chlorothiazol-5-yl or 6-chloropyridin-3-yl)
methyl -4-methyl-1h-1, 2, 3-triazol-4-yl-5-carbonyloxy substituted methyl phosphonates Xiao-Bao
Chen, De-Qing Shi·············································································································································353
P-110 Determination of orgranophosphorous pesticides using phosphorous ionic liquid as extraction
and LPME-HPLC Xie Hongxue, He Lijun, Wang Meimei, Wu Xiuling, Wu NaNa········································354
P-111 Synthesis and thermal property of bis(1-oxo-2,6,7-trioxo-1-phosphabicyclo[2,2,2]octane
-4-methanoic)-2,2-dimethyl-1,3-propanediester Xi-Jun Sheng, Zheng-Qiu Li, Hong-Wu He···················356
P-116 The improved method for the industrial scale preparation of adenosine cyclophosphate (cAMP)
Xiu Qiang Wang, Dong Chao Wang, Ran Xia, Zhi Guang Zhang, Hai Ming Guo, Gui Rong Qu······························357
P-122 Synthesis and herbicidal activity of α- [2-(fluoro-substituted phemoxy)-propionyloxy]
alkylphosphonates Yan-Jun Li Hong-Wu He·························································································358
P-126 Synthesis, crystal structure and bioactivities of dimethyl[(3,7-dichloroquinolin-8-yl carbonyloxy)
alkyl] phosphonate Ying Liang, Ya-Zhou Wang, Hong-Wu He ··································································359
P-131 Long-persistent fluorescent films of europium and dysprosium co-doped aluminates Yuan Ming Huang,
Fu-fang Zhou ····················································································································································362
P-133 Ab initio study on the toxicity of organic phosphorus agrochemical Zhang Yu·······························362
P-136 Pattern of sediment phosphorus fractions in a shallow wuliangsuhai lake, China: effects of
macrophytes Zhenying Liu, Zhaohui Jin, Yawei Li, Tielong Li, Jiujun Gu, Si Gao, Xiaoyu Chai ···················363
P-166 New functionalized phosphoryl membrane carriers of organic and nonorganic substrates
Krasnova N.S., Garifzyanov A.R., Cherkasov R.A.································································································364
P-173 High throughput screening under Zinc-database and synthesis a dialkylphosphinic acid as a
potential KARI inhibitor Liu Xinghai, Chen Peiquan, Guo Wancheng, Wang Suhua, Li Zhengming·················365
P-191 Investigation on the peptides formation from amino acids reacted with trimetaphosphate by
LC-MS Xiang Gao, Yan Liu, Pengxiang Xu, Guo Tang, Yufen Zhao ····························································369
Symposium 8
SPECIAL SESSION DEDICATED TO THE LATE PROFESSOR L. HORNER
KL-4 Olefination reaction in organic sulfur chemistry and synthesis of natural products Marian Mikolajczyk ···371
XVII

IL-3 2-hydroxy- and 2-amino-functional arylphosphines-synthesis, reactivity and use in catalysis J. Heinicke,
W. Wawrzyniak, N. Peulecke, B. R. Aluri, P.G. Jones, S. Enthaler, M. Beller ······················································372
IL-4 Enantioselective synthesis of P-chirogenic phosphorus compounds via the ephedrine-borane
complex methodology Sylvain Juge·········································································································373
IL-5 Umpolung in Horner reaction: phosphoramidates as a source of P-chiral organophosphates
Wojciech Jacek Stec and Janina Baraniak···········································································································375
IL-6 Synthesis and applications of phosphonates prepared from electrophilic phosphorus reagents
David F. Wiemer ···············································································································································376
IL-7 Development of novel chiral phosphorus ligands for enantioselective homogeneous and
heterogeneous catalysis Kuiling Ding·····································································································377
O-34 Chiral phosphorus-contained calixarenes S.O.Cherenok, V.I.Boiko, V.I.Kalchenko ······························379
AUTHOR INDEX .............................................................................................................. 381
XVIII

Plenary Lecture

PL-1
STRUCTURE AND REACTIVITY OF INORGANIC PHOSPHORUS COMPOUNDS
Francois Mathey
Physical Sciences Unit 1 424, University of California, Riverside, CA 92521, USA
This lecture highlights a few recent developments in organophosphorus chemistry. A first
identified trend is directed toward very simple molecules such as P2 and PC - . A second trend is
directed toward complex molecules such as organophosphorus polymers and phosphaporphyrins. A
third trend concerns new applications such as hydrogen storage, optoelectronic devices and killer
cells growth.
1

PL-2
PHOSPHATE - THE CORNERSTONE OF LIFE
G. Micheal Blackburn
Krebs Institute, Department of Chemistry , Sheffield University, Sheffield, S3 7HF, UK
Phosphate monoesters and diesters have well-known roles in genetic materials, in co-enzymes, in
energy reservoirs, as intermediates in biochemical transformations, and in the regulation of
biological activity through protein phosphorylation. Their enormous kinetic stability is at the heart
of these functions. Alkyl phosphate dianions have rates of spontaneous hydrolysis of 2 x 10 -20 s -1
and dimethyl phosphate has kuncat 10 -15 s -1 at 25˚C. Thus, enzymes that hydrolyse or transfer the
phosphoryl group manifest some of the largest rate accelerations known. Staphylococcal nuclease
accelerates P-O bond fission by at least 10 16 -fold while phosphate monoesterases show rate
accelerations ~10 21 -fold in some cases.[1,2]
Investigations of enzyme mechanisms have been very successful in defining the stereochemistry
of phosphoryl group transfer – usually inversion of configuration with some examples of retention
involving double inversion). Kinetics, isotopic methods, pH-rate profiles, and other physical
organic chemistry tools have sought generally to differentiate between three possible mechanisms:
• A dissociative, SN1-type mechanism (DN + AN, in IUPAC nomenclature) that involves a stable
metaphosphate anion PO3 – ;
• An associative, two-step, addition–elimination mechanism (AN + DN) that involves a
penta-covalent phosphorane intermediate; and
• A concerted. SN2-like mechanism (ANDN) with no intermediate.
In purely chemical reactions, phosphate monoesters generally follow a dissociative pathway with a
loose transition state while phosphate diesters usually react via a synchronous transition state.[1]
X-ray structures of enzymes that catalyse phosphoryl transfer reveal that they share limited
similarity through having positive charge in the active site, either from cationic amino acid
side-chains (His, Lys, Arg) or from metal ions (Mg, Zn, etc), but little else. Because of the
difficulties in separating effects of systematic structural variation of substrates on Km and kcat,
general physical methods have provided results that are less clear-cut than for model systems.[1] As
a result, much reliance has been placed on the interpretation of structures of complexes of enzymes
with substrate or product analogues to give mechanistic information, though this is unavoidably
based on a ground-state complex. Approaches to transition states have been hampered by the
instability of acyclic dialkyl pentaco-ordinate phosphoranes and the absence of alternative, reliable
transition-state analogues. Among the most successful, the aluminium tetrafluoride anion has
provided structures of several enzyme complexes, although it necessarily has an octahedral
aluminium core replacing a pentacovalent phosphorus species.
Magnesium trifluoride, MgF3 – , has been assigned [3,4] and under-assigned [5] as the molecular
core seen in X-ray structures of trigonal-bipyramidal species (TBP) of enzymes catalysing
phosphoryl transfer. A structure of ß-phosphoglucomutase (ßPGM) complexed with glucose
6-phosphate (G6P) has been mis-represented as a pentacovalent tbp phosphorus intermediate [1,5]
while our alternative interpretation of MgF3 – as the core tbp species[6], endorsed by computational
analysis,[7] was at first rejected [8] but later fully substantiated. Kinetic, spectroscopic, and
structural data confirm MgF3 – as a TSA for ßPGM.[9] Fluoride is a potent inhibitor for ßPGM and
2

19 –
F NMR analysis shows three F ions are recruited into the active site of the enzyme in the
presence of G6P. NOE analysis using 15 N, 2 H-labelled identifies 5 amino acids in close contact with
two fluorides while the third F – is co-ordinated to a catalytic Mg 2+ ion and to the hexose 2-OH
group. These data [9] accurately locate the binding site for the magnesium ion, which is further
co-ordinated to G6P C 1 -OH group and to Asp-8, and are totally in accord with the published X-ray
structure.[4,7]
In examples of metal fluoride complexes of phosphoryl transfer enzymes identified solely by
x-ray analysis, the presence of F – (rather than OH – ) has necessarily been inferential at the
resolutions achieved. Our results [9] thus constitute the first direct observation of a metal fluoride
complex as a TSA for a phosphoryl transfer enzyme. † The bonding in the tbp accurately portrays
the transition state for phosphoryl transfer in ßPGM and reveals the details of protein catalysis.
Because the MgF3 – species is both isoelectronic and isosteric with metaphosphate, PO3 – , it is a
near-perfect transition state analogue for phosphoryl transfer and can provide details of
mechanisms of enzyme catalysis not hitherto available. Most importantly, re-calculation of the
electron-density data for the MgF3–ßPGM complex (PDB accession 1O08 [4]) provides hydrogen
bond lengths for the transition state for phosphoryl transfer at 1.2Å resolution that show no
evidence for short, strong hydrogen bonds![11]
A kindred situation has been identified for F1ATPase [4a] which enables a direct comparison of
beryllium, aluminium, and magnesium fluoride structures.[4b, and Plenary Lecture by J.E.Walker]
Several enzyme structures have been reported in which AlF3 has been identified a tbp TSA for
phosphoryl transfer.[12] We have explored this situation for βPGM and also for a phosphoserine
phosphatase in competition with MgF 3- by 19 F NMR and will report surprising developments.[10]
They expose the risks inherent in an isolated x-ray crystallographic approach to enzyme
mechanisms for phosphoryl transfer and further illuminate enzyme mechanisms for phosphoryl
group transfer.
References
1. Cleland, W.W.; Henge, A.C. Chem.Rev., (2006) 106, 3252-3278.
2. Lad, C.; Williams, N.H.; Wolfenden, R. J. Amer. Chem. Soc. (1998) 120, 833-837.
3. Graham, D.L.; Lowe, P.N.; et al. Chem. Biol. (2002), 9, 375-381.
4. [a] Bowler, M.F.; Blackburn, G.M.; Leslie, A.G.W.; Walker, J.E. abstr. Gordon conf. Biophys. (2005). [b] “A new
intermediate in the catalytic cycle of bovine mitochondrial F1-Atpase”, Bowler, M.W.; Blackburn, G.M.; Leslie,
A.G.W.; walker. J.w.; Embo J in prepn.
5. Lahiri, S.D.; Zhang, G.; Dunaway-Mariano, D.; et al. Science (Washington, DC, USA) (2003), 299, 2067-2071.
6. Blackburn, G.M.; Williams, N.H.; et. al. Science (Washington, DC, USA) (2003), 301, 1184.
7. Webster, C.E. J. Amer. Chem. Soc. (2004) 126, 6840-6841.
8. Tremblay, L.W.; Zhang, G.; et al. J. Amer. Chem. Soc. (2005), 127, 5298-5299.
9. Baxter, N.J.; Olguin, L.F.; Golicnik, M.; Feng, M.; Hounslow, A.M.; Bermel, W.; Blackburn, G.M.; Hollfelder, F.;
Waltho, J.P.; Williams, N.H. Proc. Nat. Acad. Sci. USA, (2006) 103(40), 14732-14737.
10. Baxter, N.J.; Hounslow, A.M.; Waltho, J.P. unpublished results.
11. Blackburn, G.M.; Gamblin, S.J.; Smerdon, S.L. unpublished data.
12. Inter alia: Schlichting, I.; Reinstein, J.; Nature Struct. Biol. (1999), 6(8), 721-723.
† As opposed to a GTP hydrolase.[3]
3

Symposium 1
Phosphorus in Organic Synthesis & Stereochemistry;
Structure and Reactivity of Organophosphorus Compounds

KL-1
CHEMISTRY OF CARBAPHOSPHATRANES
Takayuki Kawashima
Department of Chemistry, Graduate School of Science, The University of Tokyo
7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan Email: takayuki@chem.s.u-tokyo.ac.jp
Main group atranes are tricyclic compounds that have transannular dative bond from nitrogen to
central main group elements as shown below. The characteristics of proazaphosphatranes
(conjugate bases of azaphosphatranes 1, a typical example of main group atranes), 1 which are
known as basic catalysts, are strongly attributable to the transannular dative bond of nitrogen to the
central phosphorus. Replacement of the dative bond by a covalent bond would supply different
reactivity and structure to the compound. From such a viewpoint, we succeeded in synthesizing
1-hydro-5-carbaphosphatrane 2 as the first main group atrane derivative bearing a 1-5 covalent
bond, which has the perfectly “anti-apicophilic” arrangement. 2 Here we report the synthesis,
structures, and reactions of 1-hydro-6-carbaphosphatrane 3 3 containing a novel tetradentate ligand
with three six-membered rings and its tautomer 4 as well as their comparison with those of
5-carbaphosphatrane 2.
In sharp contrast to 1-hydro-5-carbaphsophatrane 2, 1-hydro-6-carbaphosphatrane 3 was
obtained as a mixture with its tautomer, phosphonite 4. Interestingly, single crystals of 3 and 4
were obtained by the slow evaporation of saturated solutions of a mixture of 3 and 4 in ether or
benzene, respectively, whose crystal structures were determined by X-ray crystallographic analysis.
Oxidation and sulfurization reactions using the mixture of 3 and 4 were found to proceed
quantitatively via trivalent tautomer 4, whereas quantitative hydride abstraction using
triphenylmethyl cation proceeded via pentacoordinate tautomer 3. Theoretical calculations as well
as other reactions including radical reactions will also be discussed.
X
X
1
E
N
5
2
X
3
4
main group atranes
E= main group element
X= O, NR
R
R
N
N
H R
P
N
1
N
+
R
R
O
O
5
H
P
C
O
R
R
R
O
O P
C
H
O
R
O
O
R
R
2 (R= t-Bu) 3 (R= t-Bu) 4 (R= t-Bu)
References
1. J. G. Verkade, Coord. Chem. Rev. 1994, 137, 233.
2. J. Kobayashi, K. Goto, T. Kawashima, J. Am. Chem. Soc. 2001, 123, 3387; J. Kobayashi, K. Goto, T. Kawashima, M.
W. Schmidt, S. Nagase, J. Am. Chem. Soc. 2002, 124, 3703.
3. S. Nakafuji, J. Kobayashi, T. Kawashima, M. W. Schmidt, Inorg. Chem. 2005, 44, 6500.
P
C
R
OH

KL-2
DEVELOPMENT METHODS SYNTHESIS OF POLYHETEROPHOSPHACYCLANES
WITH ENDOCYCLIC P-C BOND ON THE BASIS OF FUNCTIONALIZED
ALKYLPHOSPHONATES(-PHOSPHINATES)
M.A.Pudovik, N.A.Khailova, R.Kh.Bagautdinova, S.A.Terent’eva, L.K.Kibardina
A. E. Arbuzov Institute of Organic and Physical Chemistry, Kazan Scientific Centre of the Russian Academy of
Sciences, Arbuzov Str. 8, 420088 Kazan, Russian Federation
Within the direction, devoted evolution methods synthesis of polyheterophosphacyclanes with
endocyclic P-C bond, two approaches.have obtained a development First is based on the reactions
of intramolecular cyclization of polyfunctional phosphonates(-phosphinates), where phosphorus
atom is connected with halogenalkylgroups, in combination with other structural fragments (ureas,
thioureas, thiouretanes, thioamides etc.). They can be easily obtained by addition proton
nucleophiles to chloromethylphosphonylated(-phosphinilated) isocyanates or isothiocyanates.
Polyfunctional P(IV) derivatives in most cases at the presence of a base undergo intramolecular
cyclization with the formation of saturated or unsaturated cyclic structures with endocyclic P-C
bond.
R
Hal(CH2)n PNCX
Y
+ ZH
R
Hal(CH2)n PNHC(X)Z
Y
B
-B . HCl
Y
R P
(CH2) n
N
X
Z
n= 1; 2 X=O; S Y= O; S Z= NH2; NHAlk; NAlk2; OR; SR; Ph2P Hal= Cl; Br
O
O
X
H
PhO
HalCH2 PNCS
ROH PhO
HalCH2 PNHC(S)OR
-RCl
PhO P
N
S
C=O
In a number of cases reactions proceed stereoselectively with the preferred formation one of the
diastereomers; that has allowed to obtain cyclic compounds in optically pure stste.
For example, as a result of the reaction chiral O-phenyl(chloromethyl)isothiophosphonate with
(R)-(+) or (S)-(-) (1-phenyl) ethylamines 2-(1-phenyl)ethylamino-4-thioxo-4-phenoxy
-1,3,4-thiazaphosphol-2-ines were isolated in optically pure form.
Ph
(PhO) 2P(O)CHNHMe + ArNCX (PhO) 2P(O)CHN-C-NHAr
X= O; S
6
Ph
Me
X
PhO
O
P
Ph
CH
N Me
-PhOH N
Ar C
Second approach is based on the employment α- and β-aminoalkylphosphonates as the basic
compounds, including optically active. As a result of addition them to isocyanates or
isothiocyanates phosphorus containing ureas or thioureas are formed, which are cyclized with
evolving of phenol molecule.
Acknowledgement. This study was supported by the Russian Foundation for Basic Research (grant
no. 06-03-32085).
X

KL-3
RINGS AND CAGES DERIVED FROM PHOSPHA-ALKYNES
John Nixon
Chemistry Department, School of Life Sciences, University of Sussex, Falmer, Brighton, BN19QJ, Sussex, UK
Phosphaalkynes, typified by Bu t CP, are excellent building blocks for synthesising a range of
unsaturated organophosphorus rings systems as well as cages. The lecture will discuss the
4-membered 1,3-diphosphacyclobutadiene ring, 5-membered polyphospholyl ring anions P3C2Bu t 2
and P2C3Bu t 3 and the 1,3,5-triphosphabenzene, P3C3Bu t 3, including new synthetic routes and their
likely mechanisms. Some main group element and transition metal complexes will also be
discussed.
Oxidation of the ring anion P3C2Bu t 2 affords the hexaphospha-pentaprismane cage, P6C4Bu t 4
which undergoes specific insertion reactions between the two phosphorus atoms that connect the
two 5-membered rings, when treated with “carbene-like” fragments E, (E = S, Se, Te, R2M, (M
=Ge, Sn and Pb), to afford the cage compounds EP6C4Bu t 4. Ready insertion of the isolobally related
[Pt(PPh3)2] also occurs, however a different type of reaction occurs with [PtCl2] involving both
insertion into the cage and Cl migration from platinum to phosphorus . Interesting features of these
structures and their NMR spectra will be presented and discussed.
* In collaboration with Laszlo Nyulaszi, Guy Clentsmith, Matthew Francis, Mahmoud Al-Ktaifani, Peter Hitchcock,
Phil Power, Scott Clendenning, Tony Avent, Michael Lappert, Philip Merle, Philip Uiterweerd and Monte Helm. The
research was funded by the EPSRC and the Royal Society.
7

IL-1
METAL-MEDIATED P-H ADDITION AS A POWERFUL TOOL FOR THE
CONSTRUCTION OF C-P BONDS: FROM ACADEMIC INTERESTS TO
PRACTICAL APPLICATIONS
Li-Biao Han
National Institute of Advanced Industrial Science and Technology
Tsukuba, Ibaraki 305-8565, Japan; Email: libiao-han@aist.go.jp
Compared to the progress in regio- and stereocontrol in carbon-carbon bond-forming reactions,
the precise synthesis of organophosphorus compounds (efficient and controlled phosphorus-carbon
bond-forming reactions) remains rather undeveloped. This situation hampers further exploration on
the applications of these compounds in material and medicinal chemistry which demand a huge
chemical pool of structurally well defined functional organophosphorus. Since our first report on
the palladium-catalyzed addition of H-phosphonates to alkynes in 1996, we have been
concentrating on the development of practically useful new reactions for the synthesis of
organophosphorus compounds (see below). Some of them are currently being evaluated by the
industry showing that kilograms of alkenylphosphinates can be easily generated by using a trace
amount (

(d) Pd and Rh-catalyzed P(O)-H addition to isocyanides
R-NC + R'2P(O)H cat. Pd
R'2(O)P N
cat. Rh
R
HN
R'2(O)P R
9
P(O)R' 2
(e) Rh-catalyzed homo- and heterodehydrocouplings of P-H bonds
RPH2 Rh cat. (RPH) 2 + H2 Ph
(R2PH) [(R
2PH +
Rh cat.
PhSH
2P) 2]
(2) Optically active phosphorus compounds
RO
R'
R = (-)menthyl
P
O
H
Ph
1 Rp
+
R2 H P
O R
O
O
1
R2 R1 cat. [Pd]
cat. [Rh]
O
RO P
O
RO P
Pd(OAc) 2 (5 mol %),
L (7.5 mol %), additive
Dioxane, 100 oC (3) New-phosphorus containing polymers
O O
H P Ar P H
X X
R
Ph
Ph
R'
R'
O R
P O
O
1
R2 R1R2 up to 88.5% ee
cat. Rh
condition A
O
RO
P
Ph
+
H
R = (-)menthyl
cat.Ni/Ph 2P(O)OH
condition B
L =
R'
R' 2P
O
P
R
O
P
R
Fe
O
Ar P
R
O
Ar P
AIBN or base
Ph 2PSPh
stereoretention
PR 2
CH 3
H
R
R
R
n
RO P
n
+ H 2
(4) A novel new class of potent anticancer agents
New organophosphorus compounds showing strong anticancer activity towards several tumor cell
lines have been revealed (will also be presented in the poster section).
This work was partially supported by New Energy and Industrial Technology Development Organization (NEDO) of
Japan (Industrial Technology Research Grant Program in 2004).
References
T. Hirai and L.-B. Han, J. Am. Chem. Soc. 2006,128, 7422; L.-B. Han and T. Tilley, J. Am. Chem. Soc. 2006, 128,
13698; Q. Xu and L.-B. Han, Org. Lett., 2006, 8, 2099; L-B Han and C.-Q. Zhao, J. Org. Chem. 2005, 70, 10121; L-B
Han, Z. Huang, S. Matsuyama, Y. Ono and C.-Q. Zhao, Journal of Polymer Science Part A Polymer Chemistry, 2005,
43, 5328-5336; L.-B. Han, Y. Ono and H. Yazawa, Org. Lett., 2005, 7, 2909; L.-B. Han, C. Zhang, H. Yazawa, and S.
Shimada, J. Am. Chem. Soc. 2004, 126, 5080.
O
Ph
R'

IL-2
NEW SYNTHETIC APPROACHES TO THE CHIRAL CYCLIC AND MACROCYCLIC
PHOSPHINE LIGANDS
O.G.Sinyashin a , A.A.Karasik a , E.Hey-Hawkins b .
a A. E. Arbuzov Institute of Organic and Physical Chemistry, Russian Academy of Sciences, Arbuzov str. 8, Kazan,
Russia, 420088. E-mail: oleg@iopc.knc.ru
b
Institut für Anorganische Chemie der Universität Leipzig, Johannisallee 29, D-04103 Leipzig, Germany. E-mail:
hey@rz.uni-leipzig.de
Design of chiral ligands has been a central subject in the development of catalytic and
stoichiometric asymmetric reactions. However studies involving diphosphine ligands and especially
chiral polyfunctional diphosphines have mostly been focused on linear compounds; in contrast,
heterocyclic diphosphines in which the phosphorus atoms are incorporated into the ring have not
been extensively investigated, though such incorporation leads to essential differences in the
structures and the properties of acyclic and cyclic compounds. Condensation in the
three-component system of primary chiral/achiral phosphines and amines with formaldehyde is a
powerful method of constructing various heterocyclic air-stable aminomethylphosphines.
A number of enantiopure heterocyclic di- and monophosphines had been obtained via
above-mentioned condensation with chiral amines 1,2 and amino acid salts 3 (Scheme 1). Due to
heterocyclic structure of the phosphines, their asymmetric center disposed at close proximity of the
transition metal coordinated with phosphorus. It should be mentioned that phosphino amino acid
salts and their complexes are water-soluble and could be used in the biphasic catalysis.
R
P H +CH2O + H N
P
R'
O2C
N
N
CO 2
R
R 3P
R
Ph
Cl
Pt
P
R'
Me
N
N
N
R
CO2
P
P
O 2C R'
R
10
Ph
Me
N
R =
R''
Ph
Me
N
R''
Br
R'
R'' = H, Me, Pr i
OC CO
Re
R
P
P
CO
R
Fe
Fe
Ph
Me
N
The condensation of l-menthylphosphine gives us a row of chiral heterocyclic di- and
monophosphine ligands with chirality in the α-position to phosphorus atoms (Scheme 2). Lipo- and
hydrophilicity of the obtained phosphines and their complexes could be tuned by varying the
substituents on nitrogen atoms.
In order to obtain systems with asymmetrical phosphorus atoms we have studied the reactivity of
secondary diphosphines. Condensation of di(arylphosphino)ethane and chiral methylbenzylamine
with formaldehyde produces a meso-isomer of 1,3,6-azadiphosphacycloheptane 4 as a main product
(Scheme 3). The meso-isomer demonstrates relatively high lability of the phosphorus configuration.
Within few days it converted into the equilibrium mixture of meso- and rac-isomers with
predominance of one of the rac-isomers. However, analogues with a propylene chain between two
CH 2
Scheme 1

phosphorus atoms have not been described yet. We have showed that instead of the desired
eight-membered 1-aza-3,7-diphosphacyclooctanes the unusual macrocyclic
1,9-diaza-3,7,11,15-tetraphosphacyclohexadecane 5 is formed in the reaction of
1,3-bis(mesitylphosphino)propane with formaldehyde and chiral methylbenzylamine (Scheme 3).
The high yield of the macrocycle was explained in terms of covalent self-assembly.
P
N
N
N
R
P
P N
R
P
R
R
M
Cl Cl
P H +CH2O + H N
P
N
N
R
R
R =
11
CH 3
,
CO 2H
CO 2H
Cl
Cl
M
P
M = Pt, Pd
PR 3
N
N
R
R
Covalent self-assembly of macrocycles appears to be a general process in aminomethylphosphine
chemistry and is a useful method for a simple and effective one-pot synthesis of macroheterocyclic
polyphosphines with large chiral intamolecular cavities (Scheme 3).
Ph
Me
N
N
Ph
P
P
Ph
N
P
P
Ar
O
NMe
O
Ar
Ph
O
NMe
O
Me
N
N
P H +CH2O + H N
P
P
Ph
Ph
N
Ar
P
P
Ar
Financial support from Volkswagen Foundation, RFBR (No. 06-03-32754-a), Russian Science
Support Foundation and from President’s of RF Grant for the support of leading scientific schools
(No. 5148.2006.3) is gratefully acknowledged.
References
1. A.A. Karasik et al. J.Chem.Soc., Dalton Trans, 2003, 2209; 2. A.A. Karasik et al. Mendeleev Commun, 2005, 89; 3.
A.A. Karasik et al. Polyhedron, 2002, 21, 2251; 4. A.A. Karasik et al. Z. Anorg. Allg. Chem. 2007, in press; 5. R.N.
Naumov et al. Dalton Trans, 2004, 357.
N
Ar
P
P
Ar
N
Ar
Me
Me
P
Ph
Me
Me
Me
Ar
N
Me
Me
P
P
N
Ar
i-Pr
Me
i-Pr
Ph
N
P
P
N
P
i-Pr
Ar
i-Pr
i-Pr
i-Pr
Scheme 2
Scheme 3

O-1
SYNTHESIS AND PROPERTIES OF λ 5 -PHOSPHININES AND λ 5 -AZAPHOSPHININES
Aleksandr N.Kostyuk, Yurii V.Svyashchenko, Dmitrii M.Volochnyuk, Dmitrii A.Sibgatulin, Aleksandr M.Pinchuk
Institute of Organic Chemistry National Academy of Sciences of Ukraine, Murmanska Str.5, Kyiv, 02094 Ukraine
Continuing our research [1] on λ 5 -phosphinines and λ 5 -azaphosphinines we have further
investigated the reaction of phosphine 1 bearing an enamine residue with alkylating agents. The
phosphonium salts 2 were found to react differently with bases. While the salts 2 upon treatment
with aqueous sodium hydroxide transformed into stable ylides 3, heating the salts 2 with a catalytic
amount of triethylamine lead to cyclic phosphonium salt 4.
We have investigated various reaction conditions under which both the ylides 3 and the
phosphonium salts 4 were converted into λ 5 -phosphinines 5. Thus, we have found a new approach
to λ 5 -phosphinines. This approach could be applied for the synthesis of λ 5 -azaphosphinines 7.
Other types of phosphinines and mechanisms of their formation will be also discussed.
Reference
[1] A.N.Kostyuk, Y.V.Svyaschenko, D.M.Volochnyuk Tertrahedron, 2005 Vol.61 pp 9263-9272.
12

O-2
THE SYNTHESIS AND SPECTROSCOPIC PROPERTIES OF spiro-ansa-spiro
PHOSPHAZENES
Amgalan Natsagdorj*, Selen Bilge**,Semsay Demiriz**,Zeynel Kilic**
* Department of Chemistry, Mongolian National University, 210646 -Ulaanbaatar, Mongolia
** Department of Chemistry, Ankara University, 06100 Tandoğan-Ankara, Turkey
Cyclophosphazene derivatives and polyorganophosphazenes are in the borderline inorganic,
organic and high polymer chemistry. It has been used in the preparation of novel phosphazene
derivatives with different substituents. The condensation reactions of NxOy-donor type
aminopodands (x, y=2,3,4) with N3P3Cl6 in dry THF yield partially substituted spiro-ansa-spiro,
spiro-bino-spiro phosphazenes, respectively.
The structures of the compounds have been examined by FTIR, 1 H-, 13 C-, 31 P-NMR, HETCOR,
MS and elemental analyses.
References
[1] Bilge, S., Natsagdorj, A., Demiriz, Ş., Caylak, N., Kılıc, Z., Hokelek, T., Helv. Chim. Acta, 2004, 87, 2088.
[2] Tercan., B., Hokelek, T., Bilge, S., Natsagdorj, A., Demiriz, Ş., Kılıc, Z., Acta Cryst., 2004, E60, 795.
13

O-3
ACETYLENEPHOSPHONATES: REACTIONS WITH NUCLEOPHILES
B.I. Ionin, A.V. Dogadina, A.V. Aleksandrova and N.G. Didkovskii
St. Petersburg State Technological Institute26 Moskovskii pr., St. Petersburg 190013, Russia.
E-mail: bi@thesa.ru
Acetylenephosphonates are accessible compounds, in much due to our earlier investigat-ions.
This report concerns mainly three groups of such compounds, namely
chloroacetyl-enephosphonates 1, aminoacetylenephosphonates 2 and acetylenediphosphonates 3.
O
(AlkO) 2P
O
Cl (AlkO) 2P NR2 (AlkO) 2P P(OAlk) 2
1 2 3
We found that in many cases the classical reactions of these compounds with nucleophiles
proceed with certain features not observed earlier for related carboxylates. Reaction of neutral
nucleophiles with chloroacetylenephosphonates 1 results in substitution of chlorine, and by this
route were prepared compounds 2 and 3. With primary t-butylamine reaction is accompanied by
hydrogen transfer with formation of ketenimine 4 but t-butylphosphine produces
phosphinoacetylenephosphnates 5; other primary amines afford amidines 6.
O
O
O NR
(AlkO) 2P
o NBu-t (AlkO) 2P
14
PHBu-t
O
(AlkO) 2P
4 5 6
With carbanionic nucleophiles formed in situ in the reaction of 1 with 1,3-dicarbonyl compounds
(e.g., dimedone, acetylacetone, malonates, malonic dinitrile) in acetonitrile in the presence of
K2CO3 reaction proceeds much similarly. Initially the product of chlorine substitution is formed,
which can transform to allene, registered as intermediate or final compound. In the case of malonic
dinitrile second molecule of the nucleophile is added to the activated multiple bond. In many cases
the compound formed captures potassium cation to give finally a stable carbanionic compound (7,8).
Similar ejection of H + rather than K + with formation of stable carbanion 9 occurs at the addition of
malonate carbanions to the triple bond of diphosphionate 3, as evidenced by means of 13 C NMR
spectroscopy (with and without proton decoupling) and x-ray structural investigation.
O
(AlkO) 2P
_
O
O
K +
(AlkO) 2P
O NC
K +
CN
CN
_ (AlkO) 2P
CN
O
NC _
O
K +
CN
O
NHR
P(OAlk) 2
7 8 9
The reasons for retention of stable carbanions (enhanced CH-acidity and formation of a cavity by
electron-donor groups) is discussed on the basis of B3LYP calculations and experimental
observations.
Addition of primary and secondary amines to inamines 2 and to other acetylenephos-phonates
leading to enamines, enediamines, amidines and heterocycles is considered.

O-4
NEW INSIGHTS IN P-NUCLEOPHILE ADDITIONS ONTO UNSATURATED IMINO
DERIVATIVES FOR THE SYNTHESIS OF P-ANALOGUES OF GLUTAMIC ACID
Christian V. Stevens,* Kristof Moonen and Ellen Van Meenen
Research Group SynBioC, Department of Organic Chemistry, Faculty of Bioscience Engineering, Ghent University,
Coupure links 653, B-9000 Gent, Belgium.
Email: Chris.Stevens@UGent.be
Aminophosphonates and aminophosphonic acids play a very important role in agrochemistry as
well as in medicinal chemistry because they are structural mimetics of the transition state during
peptide hydrolysis. Therefore, several aminophosphonic acids and azaheterocyclic phosphonates
have excellent fysiological activity as enzyme inhibitor.
A major synthetic route for aminophosphonates is the addition of phosphites to imines and many
different conditions have been described. The addition of phosphites to α-unsaturated imines was
previously described to yield selectively 1,2-adducts.
We have now developed a new acid promoted addition of phosphites to α-unsaturated imines
leading to α-difosfono-amines. The tandem addition involves a reversible 1,2-addition followed by
a 1,4-addition leading to the new class of phosphono aminophosphonates. This new reaction allows
the synthesis of a variety of phosphorus analogues of glutamic acid which are of great importance
for the study of ionotropic and metabotropic glutamate receptors.
R 1
R 1
N R2
H +
H
N R2 H
Pathway A
1,4-addition
H
HN R2
R P
3 R
O
3 O OTMS
R 1
1,2-addition
POTMS(OR 3 ) 2
H
R 1
R 1
N R2
TMS
H
N R2 H
P(OR 3 ) 2
O
OR
P
3
OR 3
OTMS
Pathway B
SN'-like substitution
-POTMS(OR 3 ) 2
N R2
R P
3 R
O
3 O OTMS
R 1
H
15
N R2
(R 3 OTMS O) 2P
R 1
Aqueous work-up
H
(R 3 O
O) 2P
R 1
HN R2
P(OR 3 ) 2
O
R 1
N R2
(R 3 OTMS O) 2P
P OR3
OR 3
TMSO
The methodology was also studied in detail on hydrazones and oximes.
Further, it was shown that this difosfonylation methodology also could be applied on the method
of Savignac for the synthesis of α-phosphono aldehydes. The steric bulk of the N-substituent
determines the sequence of the 1,2 versus 1,4-addition of silylated phosphite or trialkyl phosphite.
References
Moonen, K.; Laureyn, I., Stevens, C.V. Chem. Rev. 2004, 104, 6177 – 6215.
Moonen, K.; Van Meenen, E.; Verwée, A.; Stevens, C.V. Angew. Chem. Int. Ed. 2005, 44, 7407 – 7411.
Stevens, C.V.; Van Meenen, E.; Moonen, K.; Verwée, A.; Rottier, M., J. Org. Chem., Submitted.

O-5
A FACILE AND HIGHLY EFFICIENT METHOD FOR Α-AMINO PHOSPHONATES VIA
THREE-COMPONENT REACTIONS FROM ARYL AZIDES CATALYZED BY
IRON-IODINE IN THE ABSENCE OF SOLVENT
You Huang *, Yaqin Yu, Tanglin Liu, Dexin Feng and Ruyu Chen
Institute and State Key Laboratory of Elemento-Organic Chemistry, Nankai University, Tianjin, 300071
α-Amino phosphonates constitute an important class of biologically active compounds, and their
synthesis has been a focus of considerable attention in synthetic organic chemistry as well as in
medicinal chemistry. 1 Most synthetic methods reported utilize reactions of imines with phosphorus
nucleophiles. Recently, it has been shown that three-component reactions of aldehydes (or ketones),
amines, and diethyl phosphite were efficiently promoted by catalytic amounts of Lewis acids . 2 and
Brosted acid, 3 or under microwave conditions. 4 Although these procedures do not require the
isolation of the unstable imines prior to the reactions, longer reaction times are necessary to obtain
the desired products in good yields at room temperature. In addition, the use of harmful organic
solvents such as CH2Cl2 is undesirable from the viewpoint of today’s environmental consciousness.
On the other side, in the three-component reactions, only primary or secondary amines were used as
the amine components, to the best of our knowledge, there are no reports that the azides are used in
this kind reaction. In the course of our investigations to develop environmentally friendly synthetic
methods of organophosphorus compounds, we have found that iron-iodine system function as
effective catalysts for the three-component reactions of aldehydes, azides, and diethyl phosphite in
the absence of solvent afforded α-aminophosphonates in good to excellent yields (Scheme)
R 1
N 3
R 2
R 1 =H, 4-Cl, 4-CH 3
R 2 =H, 2-Cl, 3-Cl, 4-Cl,2-NO 2, 3-NO 2, 4-NO 2, 4-CH 3, etc
O
H
+ +
H
16
O
P
Scheme
OEt
OEt
neat
R 1
R 2
NH
Yield: 65-86%
References
1. Sheridan, R. P. J. Chem. Inf. Comput. Sci. 2002, 42, 103.
2. Mu,X. J.; Lei, M.Y.; Zou, J. P.; Zhang, W. Tetrahedron Lett. 2006, 47, 1125 and references cited therein.
3. Akiyama, T.; Sanada, M.; Fuchibe, K. Synlett, 2003, 10, 1463
4. Yadav, J. S.; Subba Reddy, B. V.; Madan, C. Synlett, 2001, 7, 1131
* This work was supported by and the Natural Science Foundation of Tianjin(05YFJMJC00600) and Nankai University
Fe- I 2
P
O
OEt
OEt

O-6
REACTION MECHANISM STUDIES OF SOLVOLYTIC DISPLACEMENT OF
CHLORIDE FROM PHOSPHORUS
Dennis N. Kevill, a Han Joong Koh, b and Suk Jin Kang b
a
Department of Chemistry and Biochemistry, Northern Illinois University, DeKalb, Illinois 60115-2862, USA.
b
Department of Science Education, Jeonju National University of Education, Jeonju 560-757, Korea
Phone, +1-815-753-6882; Fax, +1-815-753-4802. E-mail: dkevill@niu.edu
We are applying the extended Grunwald-Winstein equation (eqn. 1) to solvolytic displacements
at phosphorus and sulfur.
log k/ko = l N + m Y + c (1)
In equation 1, k and ko are the first order rate coefficients for solvolysis in a given solvent and in
80% ethanol, l is the sensitivity to changes in solvent nucleophilicity (N), m is the sensitivity to
changes in solvent ionizing power (Y), and c is a constant (residual) term. Previous
studies 1 of the solvolysis of phosphorochloridates, (RO)2POC1 and [(CH3)2N]2 POC1, have been
extended to cyclic phosphorochloridates, with five-and six-membered rings. Both kinetic and
product studies are performed. We will also report on kinetic studies of the solvolyses
of Ph2POC1, Me2POC1, Ph2PC1, (C2H5)2PCl, [(CH3)3C]2PCl,and (C2H5O)2PC1. The l and m
values can be compared with previous values, 1 and with values for attack at sulfur, to give useful
mechanistic information.
Reference
(1) Kevill, D.N.; Carver, J.S. Org.Biomol.Chem.2004, 2, 2040 and references cited
17

O-7
THE NEW TIPE OF CALIX[4]RESORCINES BEARING PHOSPHONATES AND
PHOSPHONIUM FRAGMENTS AT THE LOWER RIM
E.L. Gavrilova 1 , A.A. Naumova 1 , N.I. Shatalova 1 , A.R. Burilov 2 , M.A. Pudovik 2 ,
E.A. Krasil’nikova 1 , A.I. Konovalov 2 .
1
Kazan Technology University, department of organic chemistry, Karl Marx str. 68. 420015 Kazan. Russia.
Gavrilova_Elena_@mail.ru
2
A.E. Arbuzov Institute of Organic and physical Chemistry. Kazan Scientific Centre of Russian Academy of Science.
Arbuzov str. 8. Kazan. 420088. Russia
The present work deals with synthetic methodology that allows the preparation of
calyx[4]resorcines bearing phosphonates and phosphonium fragments at the lower rim, the latter
were further modifided at the upper rim with secondary and tertiary amine groups of different
structure by Mannich reaction.
The methodology of introduction of phosphorus groups based on the reaction of phosphorylation
of arylhalides by the derivatives of P(III) acids in the presence of Ni(II) compounds in which
connection two main methods of functionalization were used:
I. Preparation of phosphorus functionalized calix[4]resorcines using calixarenes matrix as the
starting material
3MeSiO
3 MeSiO
OSiMe 3
Br
3 MeSiO
Br
Br
OSiMe 3
Br
OSiMe 3
OSiMe 3P
OSiMe 3
+
RnP(軷 / 4 ) 3-n
18
NiBr 2
PhCN
?= O; R ' = Et, i-Pr; n=0
? = N; R = Ph, R' = NEt2 ; n= 0-3
HO
OH
P
HO
HO
P
OH
OH
P
? = O; P = P(O)(OR') 2
?= N; P = R n P + (NEt 2 ) 3-n Br -
chair conformation
II. Preparation of calix[4]resorcinarenes phosphorylated at the low rim using the methodology for
synthesis of octols by fourfold condensation of 4-phosphorus substituted benzaldehydes with
resorcinol
P
HO
OH
HO
OH
O
HO
OH
P = P(O)(OR') 2 ; R' = Et, i-Pr; P
P
P = RnP P
P
+ (NEt2 ) 3-nBr - ;
R = Ph; n = 0-3 bowl conformation
Isolated compounds were characterized by 31 P, 1 H and 13 C spectroscopy and date of elemental
analisis and MALDI TOF.
Acknowledgement. The support of the RFBR ( grant No. 04-03-32512 ) is gratefully acknowledged.
OH
OH
OH

O-8
MICROBIAL RESOLUTION OF RACEMIC PHOSPHONATES DERIVATIVES WITH
ONE OR TWO STEREOGENIC CENTRES
Ewa Żymańczyk-Duda, Małgorzata Brzezińska-Rodak, Magdalena Klimek-Ochab, Renata Kuriata, Marta Miszuk,
Paweł Kafarski and Barbara Lejczak.
Szybowcowa 50/17 54-130 Wrocław, Poland
Biotransformations are biocatalytic conversions of non-natural substrates to structurally diverse
products and belong to the standard means of Green Chemistry, which is the vigorously developing
field of organic chemistry [1]. Biocatalysts are applied where the chemical synthesis fails or where
compounds of required stereochemistry have to be synthesized [2]. Phosphonates constitute group
of compounds which molecules contain direct bond between phosphorus and carbon atoms. Among
them are structural analogues of carboxylic acids - they influence the activity of enzymes involved
in amino acids metabolism exerting biological effect as antibacterials, herbicides or
neuromodulators [3]. One of the most dynamically developing fields of research – not fully
explored - is microbial bioconversion of racemic – chemically synthesized starting materials - into
optically pure derivatives of organophosphorous compounds [4, 5]. Two kind of phosphonates
derivatives were used as substrates of biocatalysis: aminophosphonates with one stereogenic centre
and hydroxyphosphonate ethylbuthyl diester with two asymmetric atoms. Aspergillus niger,
Rhodotorula rubra and Rhodotorula gracilis were used as biocatalysts in kinetically controlled
resolution of aminophosphonates into optically pure products, reaction was catalysed by L- or
D-amino acid oxidase existing in fungal cells. Physiologically, this enzyme converses L- or D-
amino acid leaving the opposite one as unreacted. Every fungal strain was previously cultivated
with the addition of particular amino acid to induce the synthesis of required enzyme. This approach
allowed obtaining optically pure aminophosphonates. Desymmetrization of hydroxyphosphonate
ethylbuthyl diester – compound with two stereogenic centers required different strategies. There are
at least two ways of microbial resolution of this substrate. First one involved microbial
transesterification of vinyl butyrate with one of the optical isomers of racemic mixture of
hydroxyphosphonate – biotransformation catalyzed by Bacillus sp. in anhydrous organic solvent.
The second strategy based upon the oxidation of hydroxy – group of one of the isomers of the
substrate, using fungal strains: Saccharomyces cerevisiae and Geotrichum candidum in water
media. All microbial cells used for the resolution of hydroxyphosphonate ethylbuthyl diester were
previously cultivated under conditions which allowed to induce desired enzyme activities inside the
cells.
References
1.Kiełbasiński P, Omelańczuk J, Mikołajczyk M. 1998. Lipase-promoted kinetic resolution of racemic, P-chiral
hydroxymethylphosphonates and phosphines. Tetrahedron Asymm. 9:3283-3287.
2.Liese A, Filho MV. 1999. Production of fine chemicals using biocatalysis. Curr. Opin. Biotechnol. 10:595-603.
3.Kafarski P, Lejczak B. 2001. Aminophosphonic acids of potential medical importance. Curr. Med. Chem. –
Anti-Cancer Agents 1: 301-312
4.Żymańczyk-Duda E, Brzezińska-Rodak M, Lejczak B. 2004. Stereochemical control of asymmetric hydrogen transfer
employing five different kinds of fungi in anhydrous hexane. Enzyme Mikrob. Technol. 34:578-582.
5.Żymańczyk-Duda E, Klimek-Ochab M, Kafarski P, Lejczak B. 2005 Stereochemical control of biocatalytic
asymmetric reduction of diethyl 2-oxopropylphosphonates employing yeasts. J Organom. Chem. 690:2593-2596.
19

O-9
ADVANTAGES OF ORGANOPHOSPHORUS SYNTHESIS IN IONIC LIQUIDS:“GREEN”
APPROACHES TO USEFUL PHOSPHORUS SUBSTITUTED BUILDING-BLOCKS
I. L. Odinets a , E.V. Matveeva a , E. V.Sharova a , O. I.Artyushin a , V.A.Kozlov, D.V. Vorob’eva a , S. N. Osipov a , T. A.
Mastryukova a , G.-V. Röschenthaler b
a A.N. Nesmeyanov Institut of Organoelement compounds RAS, Moscow, Russia,
b Institute for Inorganic& Physical Chemistry, The University of Bremen, Germany
Currently, ionic liquids (ILs) due to their potential for recyclability, ability to dissolve a variety of
organic, inorganic and metal complex materials and non-volatile nature, are of interest in the search
for “green” alternatives of traditional organic solvents. Nevertheless, only a few applications of
ionic liquids in organophosphorus chemistry can be found in the literature, namely the
Wittig-Horner reaction 1a , the synthesis of α-aminophosphonates via the Kabachnik-Fields
reactions 1b,c and the esterification of phosphonic(phosphinic) acids by triethyl(methyl)
orthoacetate 1d . We would like to suggest examples of a new application of ILs as activating media
for organophosphorus chemistry. Thus, the use of [Rmim][X] enhanced significantly the rate of the
Michaelis-Arbuzov rearrangement to give the target products in high yields under mild conditions
with short reaction times. The method described can be successfully combined in a one-pot
synthesis with the BASIL TM procedure 2 used for the synthesis of trivalent phosphorus acid esters.
Ph2P(O)R' 90% - quant
[hmim]Br
r.t., 30 min
R=Ph
R 2POEt + R'X
20
[bmim]NTf 2
110
R=OEt
o C, 20 min
(EtO) 2P(O)R'
93- 95%
The second example comprises the direct synthesis of a variety of carbamoylmethyl phosphine
oxides (CMPO) useful for processing of liquid radioactive wastes. In this reaction phosphonium ILs
can be successfully applied similar to imidazolium ones. In the case of polymeric materials
modified by amino functions this procedure gives chemically stable membranes bearing
CMPO-moieties for water cleaning.
R1R2P(O)CH2COOH R1R2P(O)CH2CONR3R4 R (PhO) 3P/IL
3 R 4 NH/
110 quant.
o C, 30min-1 h
R ;
1 ,R2 = OAlk, Alk, Ph R3 ,R4 = H, Alk, Ar, CH2Ar Furthermore, phosphorylated azides interesting as substrates for the ‘click’ chemistry approach
may be readily obtained via nucleophilic substitution of ω-halohenoalkylsubstituted phosphorus
compounds.
R 1 R 2 P(O)(CH 2) nHlg
NaN3/H2O/[bmim]PF6 r.t.
R1R2P(O)(CH2) nN3 N
N
N
(CH2) nP(O)R 1 R 2
R
R
In all the above reactions the recovered ionic liquid may be recycled at least 5 times without any
decrease in activity. The influence of the anion on the activity as well as reasons of activation by
ILs and non-typical reaction course in some cases will be discussed based on detailed investigation
of the reaction mechanisms and intermediates formed.
Reference
1. a) Kryshtal, G. V.; Zhdankina, G. M.; Zlotin, S. G. Mendeleev Commun. 2002, 176.b) Lee, S-gi; Park, J. H.; Kang, J.;
Lee, J. K. Chem. Commun. 2001, 1698. c)4. Yadav, J. S.; Reddy, B. V. S.; Sreedhar, P. Green Chem. 2002, 4, 436. d)
Yoshino, T.; Imori, S.; Togo, H. Tetrahedron Lett. 2006, 62, 1309.
2. PCT Int. Appl. 2003, WO 2003062251; Chem. Abstr. 2003, 139, 149757.

O-10
SYNTHESIS AND CHEMICAL PROPERTIES OF BENZO[E]-1,2-OXAPHOSPHORININE
DERIVATIVES – P-ANALOGUES OF COUMARINES
E.N.Varaksina, D.A.Tatarinov, K.Yu.Cherkin, V.F.Мironov, A.I.Konovalov
A.E.Arbuzov Institute of Organic and Physical Chemistry, Russian Academy of Sciences, Arbuzov Str. 8, Kazan,
420088, Russia, e-mail: vlena@iopc.knc.ru
The chemistry of the Р-heterocycles with О–Р–С or N–P–C bonds is one of the important fields
of organophosphorus chemistry. It is mainly connected with the possibility of obtaining of various
biologically active compounds. Recently, we have offered an easy method for selective synthesis of
the new type of Р-heterocycles (3) by reaction of phosphorylated catechols with terminal alkynes.
The unusually easy transformation (the reaction proceeds at room temperature with the quantitative
formation of compounds 3) of dioxaphosphole cycles to 1,2-oxaphosphorinine includes the
uncatalyzed phosphaalkylenes fragment formation, the aromatic fragment halogenation and
ipso-substitution of oxygen. The regiochemistry of these processes mainly depends on the nature of
R, R 1 , R 2 substituents. It was shown that the phosphonium salts and cationic or anionic
phosphorates are able to interact with acetylenes and give the close result. The reaction with
phosphonium derivatives is turned out to be a classical addition of phosphorus halides to the
carbon-carbon multiple bonds.
The chemical properties of obtained phosphorinines (3) were investigated for the first time. The
new functionalized P-analogues of natural coumarines were obtained. Among them the series of
stable cyclic phosphonous acids and amines can be mentioned. The halogenation and alkylation
reactions may proceed both with phosphorus atom and double carbon-carbon bond depending on
the halogenation or alkylation reagents nature. Another unusual result is rather easy conversion of
compounds (3) to phosphoranes (4) or to phosphonium salts (5) with the same or different
substituents Y, Z, W.
R1
R2
1
OH
OH
R1
R2
X = Cl, Br; R = Alk, Ar
O
HC CR
PX3
O
2
21
X
R1
R2
3
O O
P
X
R
X
R1
R2
5
X
R1
R2
O +
P
R
4
Y
Z
O P W
The offered method is a versatile approach for modification of the natural catechols and
dihydroxy-derivatives of heterocycles as well as for a wide range of acetylenes.
The work is supported by Russian Science Support Foundation and the МК-1434.2006.3
program.
R
Y Z

O-11
THE REACTION OF 1,2-NAPHTHOQUINONES WITH SOME P(III) DERIVATIVES –
A VERSATILE SYTHETIC APPROACH TO POTENTIALLY USEFUL
NAPHTHOQUINONES AND DIHYDROXYNAPHTHALE-NES CONTAINING
PHOSPHORUS–CARBON BOND
A.V.Bogdanov, V.F.Мironov, N.R.Khasiyatullina, D.B.Krivolapov,
I.А.Litvinov, А.I.Konovalov
A.E.Arbuzov Institute of Organic and Physical Chemistry, Russian Academy of Sciences,
Arbuzov Str. 8, Kazan, 420088, Russia, e-mail: mironov@iopc.knc.ru
As a rule, trivalent phosphorus compounds are used in chemistry of ortho-quinones for the
synthesis of phosphoranes or phosphonium salts containing P + –OС bond. The reactions of
1,2-naphthoquinones with P(III) derivatives have been insufficiently investigated by the time. The
reaction of 1,2-naphthoquinones with phosphites was only reported to give pentaalkoxy
phosphoranes. Here the reactions of 1,2-naphthoquinones with such P(III) derivatives as
tris(diethylamino)-, tri(n-butyl)- and triphenylphosphines were investigated for the first time. The
reactions unexpectedly give betaines 5-8 containing phosphorus moiety in the fourth position of
naphthalene cycle with high yields. The treatment of compounds 5-8 with bromine or hydrogen
halide yields corresponding quinone- or catechol-containing phosphonium salts 9-12.
(Et2N)3P
+
O
O R2
R2 R1
1-4
O
H
O Hal2
_
or HHal
R1 R2
+
P(NEt2)3
_
Hal
OH
OH
+ (or)
R1 R2
+
P(NEt2)3
5-8
9, 10, 12
R1, R2 = H, H (1, 5, 9), Br, H (2, 6, 10), H, Br (3, 7, 11), Cl, Br (4, 8, 12),
22
O O
_ R1
Hal
+
P(NEt2)3
11
Hal = Cl, Br, J
The reactions of the 3-substituted 1,2-naphthoquinones with tri(n-butyl)- and triphenylphosphines
preferably lead to the formation of 1,1’,2,2’-tetrahydroxy-3,3’-dihalogeno-4,4’-binaphthyls, which
give the stable complexes with two molecules of phosphine oxide.
O O
R2 R1
2, 4
R = Ph, n-Bu
PR3
H2O
OH OH
R2 R1
R1 R2
HO OH
13-16
. 2 O=PR3
The structure of compounds 5-11 has been confirmed by NMR and single crystal X-ray diffraction
(for compounds 9, 12). The work is supported by the DCMS program N. 1 of Russian Academy of
Sciences.

O-12
YLIDES AND CARBENES. THE FIRST CARBENE CATALYZED REACTION
Shevchenko I.V.*, Rogalyov A.E., a Poliakov D.V., a Röschenthaler G.-V. b
a Institute of Bioorganic Chemistry and Petrochemistry, Murmanskaya Street 1, 02660 Kiev, Ukraine
b Institute of Inorganic and Physical Chemistry, University of Bremen, Leobener Str, 28334 Bremen, Germany
The P=C ylidic bond of phosphorus ylides is able to dissociate with the formation of the
appropriate phosphanes and carbenes.
P P
For example, ylide 3 obtained from diphosphane 1 and acyl imines 2 is capable of reversible
cleavage of the P=C bond in solution to give carbene (nitrile ylide) 4 and the phosphane,
respectively. Carbene 4 can be trapped by Ph3P to give ylide 5. Trying to obtain ylide 5 from Ph3P
and acyl imine 2 we found that under certain conditions the reaction leads to the formation of
difluorophosphorane 6 and carbene 7. The latter can display not only carbene-like but also
biradical-like properties to give dimer 8.
Ylides 3 and 5 can be used as a source of carbene (or nitrile ylide) 4 in different reactions under
mild conditions. However, the interaction of ylide 5 with diaminocarbene 9 did not give the
expected alkene 10, but led to a quantitative transformation into compound 11 which can be
considered as an unsymmetrical dimer of carbene 4. This is the first example of a reaction in which
carbene acts as a catalyst.
Similarly to phosphanes, diaminocarbene 9 can react with acyl imine 2. Although this reaction
should also include the intermediate formation of carbene 4, no traces of its dimer 11 were found in
this case and the only product was alkene 10.
PPh 2
Ph2P Ar N
O
N Ar C(CF
3 4
3) 2
5
C(CF3) 2
Ph 2P
O
1
N Ar
C(CF3) 2
PPh 2
(i-Pr 2N) 2C
9
23
F 3C
Ph3P Ar N
(F3C) 2C
Ph3PF2 6
F
C
i-Pr2N NPr-i2 N N
CF3 F C C F
F3C 2 10 Ar N CF3 11 Mes Mes 8
C
F
C
CF 3
CF 3
F
CF 3
C
O
N
N
N
O
7
Mes O
Mes
CF 3
F
Mes

O-13
SYNTHESIS, OPTICAL PROPERTIES AND REACTIVITIES OF A
DIBENZOPHOSPHABORIN AND ITS DERIVATIVES
Junji Kobayashi, Tomohiro Agou, and Takayuki Kawashima
Department of Chemistry, Graduate School of Science, The University of Tokyo 7-3-1 Hongo, Bunkyo-ku, Tokyo
113-0033, Japan
E-mail: jkoba@chem.s.u-tokyo.ac.jp
π-conjugated molecules with novel electronic and optical properties are desirable for constructing
organic functional materials including organic semiconductors and light emitting devices. Recently,
incorporation of main group elements into π-conjugated systems has been reported as efficient
methodology to decrease HOMO-LUMO energy gaps because of π-conjugation between π-orbitals
and donor or acceptor orbitals on main group elements. Among these classes of molecules,
boron-containing hetero π-conjugated molecules have attracted much attention because of its vacant
2p orbital, which can decrease the LUMO level and respond to external stimuli (i.e. Lewis bases).
Herein we report the syntheses and the properties of a dibenzophosphaborin and its derivatives as
the novel boron-containing hetero π-conjugated molecules.
Dibenzophosphaborin 1 was prepared from 2,2’-dibromotriphenylphosphine by the reaction with
BuLi and subsequent MesB(OMe)2. The phosphorus atom of dibenzophosphaborin 1 maintained its
reactivity as triarylphosphine and 1 was readily led to sulfide 2, selenide 3 and phosphonium salt 4
in good yields. X-ray crystallographic analysis of 1 showed the phosphaborin ring has a
butterfly-shaped structure due to the pyramidalization of the phosphorus atom.
Dibenzophosphaborin 1 showed very weak fluorescence emission with the large Stokes shift. It is
probably because of large structural difference between the ground and excited states as well as
flexibility of the phosphaborin ring of 1. Fluoride binding abilities of 1 and its derivatives 2-4 will
also be presented.
The study was partially supported by the Grant in Aid for the 21st Century COE Program for
Frontiers in Fundamental Chemistry.
24

O-14
PHOSPHINOUS ACID-BORANES:AN EMERGING CLASS OF
ORGANOPHOSPHORUS REAGENT
K. Michal Pietrusiewicz * and Marek Stankevič
Maria Curie-Sklodowska University, Department of Organic Chemistry,ul. Gliniana 33, 20-614 Lublin, Poland
e-mail: michal@hermes.umcs.lublin.pl
Despite the synthetic importance and wide use of derivatives of phosphinous acid-boranes such
as their esters (phosphinite-boranes), or acid chlorides (chlorophosphine-boranes), the parent
phosphinous acid-boranes (1) have, until very recently, remained practically unexplored and have
not been even synthesized on purpose. We have recently demonstrated that phosphinous
acid-boranes can be conveniently obtained by one of the two general synthetic routes utilizing
readily available sec-phosphine oxides or phosphinic acid chlorides as substrates. 1,2 Phosphinous
acid-boranes were then found to possess rich reactivity pattern which offered many useful synthetic
transformations through the reactions at their P, O, or B, reactivity centers. 2,3 When
unsymmetrically substituted they are P-stereogenic and can be readily resolved into enantiomers 3,4
and used subsequently as versatile substrates for the stereoselective synthesis of a wide range of
other nonracemic P-stereogenic compounds. Some examples of the stereoselective conversions of a
model (S)-t-butylpbenylphosphinous acid-borane (1a) into other nonracemic phosphorus
compounds are shown below.
O
O
Ph P
I
t-Bu
49% ee
S
Ph
P
H
t-Bu
~80% ee
P
Ph H
t-Bu
83% ee
BH 3
BH 3
P OH
t-BuPh
(S)-(-)-1a
25
Ph P
Me
t-Bu
100% ee
BH 3
BH 3
BH 3
Ph P
H
t-Bu
100% ee
BH 3
P H
t-BuPh
O
100% ee
t-Bu P
Ph
O S Me
O
Ph P
OMe
t-Bu
100% ee 100% ee
The readily available resolved phosphinous acid-boranes hold thus great promise as the new
enantiopure reagents for stereoselective synthesis of other phosphorus compounds including the
valuable enantiomerically pure phosphines. Further examples will follow.
References
1. Stankevič, M.; Andrijewski, G.; Pietrusiewicz, K. M. Synlett 2004, 311.
2. Stankevič, M.; Pietrusiewicz, K. M. Synthesis 2005, 1279.
3. Pietrusiewicz, K. M.; Stankevič, M. Curr. Org. Chem. 2005, 9, 1883.
4. Stankevič, M.; Pietrusiewicz, K. M. J. Org. Chem., 2007, 72, in print.

O-15
SYNTHESIS OF NEW FUNCTIONALIZED PHOSPHORUS SUBSTITUTED
DERIVATIVES OF 2,6-DI-TERT-BUTYL-4-METHYLPHENOL
A.A. Prishchenko, M.V. Livantsov, O.P. Novikova, L.I. Livantsova, E.R. Milaeva
Department of Chemistry, M.V. Lomonosov Moscow State University, Moscow, 119992, Russia. E-mail:
liv@org.chem.msu.su
Sterically hindered phenols are widely used for preparation of stable phenoxyl radicals and also
are well known antioxidants. We have developed the convenient methods of synthesis of new
functionalized phosphorus substituted derivatives of 2,6-di-tert-butyl-4-methylphenol (ionol) which
are of great interest as perspective antioxidants, chelating ligands and bioactive substances with
various properties. So the phosphonite A and phosphonates B are obtained via smooth addition of
the bis(trimethylsiloxy)phosphine and trimethylsilylphosphites to 3,5-
di-tert-butyl-4-hydroxybenzaldehyde in high yields.
The new diphosphonates C, E and the functionalized phosphinates D, F were synthesized via
interaction of the trimethylsilyl esters of several trivalent phosphorus acids with 3,5-
di-tertbutyl-4-hydroxybenzaldichloride and 3,5- di-tert-butyl-4-hydroxybenzoyl chloride in high
yields.
The compounds A - F easily react with methanol or sodium methylate in methanol yielding the
new water soluble acids or their derivatives as perspective substances.
26

O-16
MICROBIAL DESYMMETRIZATION OF RACEMIC MIXTURE OF
(1-HYDROXYPHENYLMETHYL)PHENYLPHOSPHINATE ETHYL ESTER VIA
OXIDATION OF ONE OPTICAL ISOMER
Magdalena Klimek-Ochab, Ewa Żymańczyk-Duda, Małgorzata Brzezińska-Rodak, Paweł Kafarski and Barbara
Lejczak
Wroctaw University of Technology, Faculty of Chemistry, Department of Bioorganic Chemistry, Wyb. Wyspiańskiego
27, 50-370 Wroclaw, Poland
Biocatalysis has become a valuable tool for the synthetic chemists. Enzymatic transformations
carried out by partially purified enzymes or whole-cell catalysts are used for the production of wide
variety of products, from bulk to fine chemicals 1 . Chemoselectivity, regioselectivity and especially
stereoselectivity of biocatalysts are particularly attractive features of biotransformations, because
they allow obtaining enantiomerically pure compounds.
Organophosphonates are compounds of special interest because of the large scope of their
biological activities 2 . Phosphonic and phosphinic acids derivatives constitute a group of both
biogenic and synthetic compounds with the stable, covalent carbon to phosphorus bond. The
growing demand for enantiomerically pure products has impelled performing microbial resolution
of racemic mixtures of phosphonates 3,4 .
Two yeast strains – Geotrichum candidum and baker’s yeast were applied as biocatalysts for the
resolution of racemic substrate – (1-hydroxyphenylmethyl)phenylphosphinate ethyl ester. The
important feature of substrate used is the presence of two stereogenic centers in molecule. So, in
optically pure form, this compound is very attractive for further application as chiral building block
in chemoenzymatic synthesis. To achieve desired purpose – optically pure products of opposite
configuration – there are at least two approaches of biocatalyst cells preparation. In the first method
both G. candidum and baker’s yeast being under starvation conditions were applied as biocatalysts
for transformation of (1-hydroxyphenylmethyl)phenylphosphinate ethyl ester. The second method
involved incubation of starved yeast’s biomass in the presence of one of chemical agents – sodium
pyruvate, oxalacetic acid and methyl-iso-propyl keton to force the microbial cells to carry out
mostly the reduction of the additives. It implied the oxidation of the dehydrogenases cofactors into
oxidized form e.g. NAD + , FAD. Subsequently after the addition of the hydroxyphosphinate into the
biotransformation media, the expected oxidation of the substrate would be a part of the cofactor
regeneration system which allowed obtaining the reduced form of the dehydrogenases cofactors
(NADH, FADH2). They are the key elements for the metabolic pathways which finally result in
ATP synthesis.
The mixture of the products was analyzed by means of NMR with the addition of quinine as a
chiral discriminator. Microbial transformation resulted in the oxidation of hydroxyl group of one
optical isomer. The product – (1-oxo-phenylmethyl)phenylphosphinate ethyl ester is extremely
unstable in water so the decomposition of this compound shifts the reaction equilibrium into the
product side.
Reference
1 Schmidt A., Dordick J.S., Hauer B., Kiener A., Wubbolts M., Witholt B., 2001, Nature, 409, 258-268.
2 Kafarski P., Lejczak B., 2001, Curry.Med.Chem.-Anti-Cancer Agents, 1, 301-312.
3 Kiełbasiński P., Omelańczuk J., Mikołajczyk, M., 1998, Tetrahedron: Asymm., 9, 3283-3287.
4 Kiełbasiński P., Albrycht M., Łuczak J., Mikołajczyk M., 2002, 13, 735-738.
27

O-18
GUANIDINOPHOSPHAZENES: DESIGN AND SYNTHESIS OF A NOVEL FAMILY OF
UNCHARGED ORGANIC SUPER BASES
Alexander A. Kolomeitsev, 1 Ilmar A. Koppel, 2 Toomas Rodima, 2 Jan Barten, 3 Enno Lork, 1 Gerd-Volker
Röschenthaler, 1 Ivari Kaljurand, 2 Agnes Kütt, 2 Ivar Koppel, 2 Vahur Mäemets, 2 Ivo Leito 2
1 Institute of Inorganic & Physical Chemistry, University of Bremen, D-28334 Bremen, Germany; 2 Department of
Chemistry, University of Tartu, 51014 Tartu, Estonia; 3 Hansa Fine Chemicals GmbH, D-28359 Bremen, Germany
A principle of creating a new generation of nonionic superbases is presented. 1) It is based on
attachment of either tetraalkylguanidino-, 1,3-dimethylimidazolidine-2-imino- or
bis(tetraalkylguanidino)carbimino groups to phosphorus of the iminophosphorane group using
tetramethylguanidine or easily available 1,3-dimethylimidazolidine-2-imine. Seven new nonionic
superbasic tetramethylguanidino-substituted phosphazene bases as well as eight new
phenylsubstituted iminophosphoranes (P2- and P4-bases) and EtP2(pyr) have been synthesized.
Their base strength is established in THF solution by spectrophotometric titration. The gas-phase
basicities of several guanidino- and N',N',N",N"-tetramethylguanidino-substituted (tmg-substituted)
phosphazenes and their cyclic analogues are calculated and the crystal structures of t-BuP1(tmg) and
t-BuP1(tmg)·HBF4 are determined. The new superbases could be used as auxiliary bases in organic
synthesis and as indicators to supplement and significantly extend the basicity scale in THF towards
the more basic region. The enormous basicity-increasing effect of this principle has been
experimentally verified in the case of the tetramethylguanidino-groups in the THF medium: the
basicity increase when moving from t-BuP1(dma) (pKα = 18.9) to t-BuP1(tmg) (pKα = 29.1) is ten
orders of magnitude. A significantly larger basicity increase (up to 20 powers of ten) is expected
(based on the high-level DFT calculations) to accompany the transfer from the same t-BuP1(dma)
base in the gas phase where the three dimethylamino fragments are replaced by methylated
triguanide fragments (tmg)2C=N-. The gas-phase basicity of the resulting base
[(tmg)2C=N-]3P=N-t-Bu is predicted to exceed that of the widely used commercial t-BuP4(dma)
superbase (gas-phase basicity around 300 kcal·mol -1 ).
Reference
1)
A. A. Kolomeitsev, I. A. Koppel, T. Rodima, J. Barten, E. Lork, G.-V. Röschenthaler, I. Kaljurand, A. Kütt, I. Koppel,
V. Mäemets, I. Leito, J. Am. Chem. Soc. 2005, 127, 17656-17666.
28

O-19
PREPARATION AND CHARACTERIZATION OF NOVEL ROOM TEMPERATURE
IONIC LIQUIDS BASED ON QUATERNARY PHOSPHONIUM CATIONS ON
QUATERNARY PHOSPHONIUM CATIONS
C 2H 5
C 4H 9
Katsuhiko Tsunashima and Masashi Sugiya
Nippon Chemical Industrial Co., Ltd.
9-11-1, Kameido, Koto-ku, Tokyo 136-8515, Japan
Ionic liquids, i.e., organic molten salts with melting points below 100 °C, have been developed
for diverse uses such as non-volatile green solvents for organic synthesis, solvent extraction and
separation processes, and new electrolytes in various electrochemical systems based on their unique
physico-chemical properties. Most studies on ionic liquids have been associated with nitrogen based
ionic liquids such as imidazolium, quaternary ammonium, pyridinium, pyrrolidinium salts, etc.
However, phosphonium based ionic liquids have been rarely investigated despite their chemical,
thermal and electrochemical stabilities. We wish here to report the preparation and
physico-chemical properties of novel phosphonium ionic liquids, as a demonstration of a new group
of room temperature ionic liquids (RTILs) used as green solvents for organic synthesis and
separation processes, electrolytic media for electrochemical devices, and others.
Phosphonium ionic liquids presented in this work are based on triethylalkylphosphonium and
tri-n-butylalkylphosphonium cations as shown in Fig. 1. The preparation was followed by aqueous
anion exchange reaction of corresponding tetraalkylphosphonium halides (bromides or iodides)
prepared by nucleophilic addition of trialkylphosphines to haloalkanes in high yields.
Triethylalkylphosphonium based ionic liquids showed lower viscosities and higher electrical
conductivities than tri-n-butylalkyl phosphonium based ionic liquids. Voltammetric analysis of
triethylalkylphosphonium based ionic liquids exhibited wide electrochemical windows (-3.0 to +2.4
V versus Ag/Ag + ). Thermogravimetric analysis also suggested that most phosphonium ionic liquids
prepared were thermally stable up to nearly 400 °C. The relationship between molecular structures
and physical properties of the phosphonium ionic liquids will be discussed.
C 2H 5
P +
C 2H 5
C 4H 9
P +
C 4H 9
R 1 X -
R 2 Y -
R 1 = n-C 5H 11, n-C 8H 17, n-C 12H 25
X = N(SO 2CF 3) 2
R 2 = CH 3, n-C 8H 17, n-C 12H 25
Y = N(SO 2CF 3) 2, BF 4, PF 6, SO 3CF 3
COOCF 3, SO 3C 6H 4CH 3, SCN
Fig.1 Phosphonium ionic liquids prepared.
29

O-20
INVESTIGATING THE MICHAELIS-BECKER REACTION IN PHOSPHONIUM AND
IMIDAZOLIUM IONIC LIQUIDS
Laura K. Byington Congiardo, Ahn Vu, Erika Shaffer, W. David Stegbauer, Robert Hartsock and D. Andrew Knight*
Department of Chemistry, Loyola University New Orleans, 6363 St. Charles Avenue, New Orleans, Louisiana 70118,
USA.
We have been studying carbon-phosphorus bond formation in alternative reaction media such as
water and ionic liquids. The alkylation of secondary phosphites (H-phosphonates) using sodium
metal or sodium hydride as a base proceeds in phosphonium salt ionic liquids such as CYPHOS
IL101 (1). The same reaction in imidazolium based ionic liquids such as [bmim][BF4] (2) can be
achieved using sodium hydroxide as a base and obviates the need for highly reactive bases such as
alkali metals or alkali metal hydrides. Work-up of the reaction is straightforward and involves
removal of alkali metal salts via aqueous extraction and separation of the ionic liquid which can be
recovered and reused. In addition, our procedure does not require the use of an organic solvent
and as such represents a greener version of the classic Michaelis-Becker reaction.
P
1
5
I
30
N N CH3 BF4 2

O-21
A NEW USEFUL SYNTHETIC PATHWAY TO TRIFLUOROMETHYL PHOSPHATES
O. A. Shyshkov, A.A. Kolomeitsev and G.-V. Röschenthaler
Institute of Inorganic & Physical Chemistry, University of Bremen, Leobener Strasse, D-28334 Bremen, Germany
Salts of perfluoroalkyl phosphates are of great interest as ionic liquids [1] which can be used as
stable and innocuous solvents in various green chemistry [2] processes. Moreover, perfluoroalkyl
phosphates attract much attention as non-coordinating anions [3] and therefore can play an important
role in preparation of new highly effective catalysts and creating Li-salt batteries of improved
properties [4] .
Herein, we present convenient multistep one-pot synthesis of trifluoromethyl phosphate salts
starting from trifluoromethyl phosphine. Simple synthetic procedures and workup as well as high
yields of the desired products are the advantages of the method proposed. (CF3)6P¯ ion, the most
interesting object of the investigation, was detected by mass spectroscopy. A fluorine atom was
abstracted from the phosphate ions discussed to give formerly unknown highly reactive
trifluoromethyl phosphoranes.
Reference
[1] N. V. Ignat’ev, U. Welz-Biermann, A. Kucheryna, G. Bissky, H. Willner, J. Fluorine Chem. 2005, 126, 1150-1159.
[2] www.epa.gov/greenchemistry/principles.html
[3] I. Krossing, I. Raabe, Angew. Chem. Int. Ed. 2004, 43, 2066-2090.
[4] Sanyo Electric Co., Japan, JP 2002075441.
[5] T. Umemoto and S. Ishihara, Tetrahedron Lett., 1990, 31, 3579
31

O-22
NEW METHODS, AND STRATEGIES FOR ASYMMETRIC SYNTHESIS OF
ORGANOPHOSPHORUS COMPOUNDS
Kolodiazhnyi O.I., Guliayko, I.V, Gryshkun E.V., Kolodiazhna, A.O., Nesterov V.V., Kachkovskyi G. O.
Institute of Bioorganic Chemistry and Petrochemistry, National Academy of Sciences of Ukraine, Murmanskaia 1, Kyiv,
UKRAINE e-mail: oikol123@rambler.ru
The report will highlight one area of our current research in organic phosphorus chemistry
dealing with the development of highly stereoselective methods and reagents and their application
for the preparation of enantiopure organophosphorus compounds.
1) A strategy of multiple stereoselectivity will be illustrated as the effective method for
stereochemical control in the synthesis of organophosphorus compounds. Stereochemical control in
the formation of a stereogenic center is most crucial during fragment assembly for a synthesis of
complex products. Selection of (R)- or (S)-chiral reagents provides a means of enantioselective
control. This strategy of a chiral reagent control via additive effect of several chiral inductors will
be shown on a number of examples. The effect of multiple asymmetric induction in catalytic
processes will be reported. Such developments suggest the possibility of attaining enhanced
stereoselection upon invoking the interaction of several chiral centers in a matched asymmetric
reaction.
A
A'
Favorable attack
A'
A
32
Non-favorable attack
Matched AI Mismatched AI
2) New asymmetric reducing reagents were developed on the base of boranes and accessible
chiral natural compounds (tartaric acid, cinchona alkaloids, some natural amines) and applied for
the preparation of bioactive organophosphorus compounds (phospho-carnitine,
phospho- -amino- -hydroxybutyric acid, phospho-statins, phospho taxoids, and others)
3) On the base of quinine and aminoacids were prepared organocatalysts, which were used to
increase the stereoselectivity of phospha-aldol reaction as well as chiral phase transfer catalysts
used in asymmetric alkylation and phosphorylation reactions.
HO
HO
O
O -
H B H M+
O
O
M= Li, Na, Bu4N Recent references (selected)
1. O.I. Kolodiazhnyi Tetrahedron, 2003, 59, 5953-6018.
2. O.I. Kolodiazhnyi Tetrahedron: Asymmetry 2005, 16, 3295-3340
3. O.I.Kolodiazhnyi Russ Chem Rev 2006, 75, 254-282.
R
A'
H
A
O
H
N

O-23
IMIDOYL CHLORIDES: NEW PROMISING BUILDING BLOCKS IN SYNTHESIS OF
α-AMINOPHOSPHORYL COMPOUNDS
P. P. Onys’ko*, Yu. V. Rassukana, A. A. Sinitsa
Institute of Organic Chemistry, NAS of Ukraine, 02094 Kyiv, 5 Murmans’ka St.
E-mail: onysko@rambler.ru
Interaction of imidoyl chlorides with nucleophilic phosphorus compounds represents a
convenient approach to biologically important acyclic and heterocyclic functionalized derivatives,
containing aminophosphoryl fragments.
O
P
Cl
R N X
N
COOR'
R
N
P H
CH2 =CBrCO2Me 1,3-H
Ar
*
R N R"
R'
P
R N
H
R"
R'
O
X
S P
R
O
1. P
2.HSCH2COOH 1
R
Cl
X=C(O)R'
P
O
N
R'
O
P
X
R
NHY
Y-H
O P<
X
R N
X = RSO2 , R2PO P
R N
O
cycloaddition
R'
III
4
2
*
3
6
5
9
8
7
Y-H: R2P(O)H, ROH, RSH, enamines, electron-rich aromatic and hetroaromatic compounds
Combination of fluoro-(R = Rf) and phosphorus substituents is favorable both for easiness and
stereoselectivity of Н-transfer in phosphorylated azaallylic systems allowing preparation of
fluorinated aminophosphoryl derivatives. The phosphorylation of N-benzylimidoylchlorides (X=
PhCH2) leads to P-C bond formation accompanied by “reagent-free” reduction of C=N bond.
Transformation 1→2→3 represents a new approach in asymmetric synthesis of aminophosphonic
acids. Activated C-phosphorylated imines 7, 8 are promising synthons for the preparation of acyclic
and heterocyclic compounds incorporating aminophosphoryl fragment. Variety of transformations
is connected with possible participation in reactions of C=N bond, halogen atoms or N-substituents.
The regularities found for reactions of imidoyl chlorides with phosphorus compounds form a basis
for purposeful control of their chemoselectivity.
33

O-24
KINETICS AND MECHANISM OF THE OXIDATION OF LOWER OXYACIDS OF
PHOSPHORUS BY MORPHOLINIUM CHLOROCHROMATE
Pradeep K. Sharma
Department of Chemistry, J.N.V. University, Jodhpur 342 005, India
Email: drpkvs27@yahoo.com
Oxidation of lower oxyacids of phosphorus by morpholinium chlorochromate (MCC) in
dimethylsuloxide (DMSO) leads to the formation of corresponding oxyacids with phosphorus in a
higher oxidation state. The reaction exhibits 1:1 stoichiometry. The reaction is first order with
respect to MCC and the oxyacids. The reaction does not induce polymerization of acrylonitrile.
Reactions are catalysed by hydrogen ions. The hydrogen-ion dependence has the form: kobs = a +
b[H + ]. The oxidation of deuteriated phosphinic (DPA) and phosphorous acids (DPPA) exhibited
a substantial primary kinetic isotope effect. The oxidation was studied in nineteen different organic
solvents. The solvent effects were analysed in terms of Taft’s and Swain’s multiparametric
equations. The effect of solvent indicates the solvent polarity plays a major role in the process. It
has been shown that the pentacoordinated tautomer of the phosphorus oxyacid is the reactive
reductant and it has been concluded that tricoordinated forms of phosphorus oxyacids does not
participate in the oxidation process. A mechanism involving transfer of a hydride ion in the
rate-determining step has been proposed.
34

7O-25
FUNCTIONALIZED PHOSPHORYL COMPOUNDS: SYNTHESIS, EXTRACTION,
TRANSPORT AND IONOPHORE PROPERTIES
R.A. Cherkasov, A.R. Garifzjanov, N.S. Krasnova, A.S. Talan, L.A. Burnaeva, G.A. Ivkova
Kazan State University. A.M. Butlerov Chemistry Institute. 420008, Kremlevskaya str., 18, Kazan, Russia
The methods of the synthesis of the mono-, bi- and polyfunctional phosphonates, phosphinates
and phosphinoxydes having an α-, β- and other positions to the phosphoryl group oxygen-,
nitrogen- and sulfur-containing functional group different in their complexing abilities (FPC) were
worked out on the base of classical reactions of the organophosphorus synthesis - Kabachnik –
Fields, Pudovik, Abramov, Todd – Atterton and others.
By use of experimental and theoretical methods acid – basic properties of the obtained FPC and
their distribution constants in interphase systems water – organic solvents are investigated. It were
obtained the quantitative dependence between the distribution constants and quantity of the carbon
atoms in FPC molecules, i.e. their hydropholic – lipophilic balance. On the base of these
correlations was made selection of the metals’ ions, organic and mineral acids potential extractants.
The optimal structure of the organophosphorus extractants as well as conditions of selective
concentrations and separations of precocious metals ’ions from accompanying ions and from each
other are developed.
It was found that efficiency both liquid and membrane – transport extractions of the mineral acids
connected with the hydratation enthalpy of corresponding inorganic acid’s anion as well as of the
structure of the FPC –carrier’s molecule. The correlations between the acids’ transport efficiency
and the nature of the organophosphorus and “additional” coordination centers were established for
the membrane extraction of perchloric, oxalic, tartaric acids and ethanolamine. The phosphinoxydes,
acids of the tetracoordinated phosphorus and FPC with additional hydroxyl- and alkoxy – groups
carriers acid substrates in form of corresponding H-complexes, but in phosphorylated amines
namely nitrogen atom appears as coordination center.
The results obtained are used in the development of the new high-effective ion-selective
electrodes sensitive to ions alkaline and alkali-earth metals, and also the anion – sensitive electrodes
used for the analysis of small amounts of substances in various objects.
Acknowledgments –The work is maintained by RBRF (grant no 04-03-3296) and a joint Russian-American Program
“Basic Research and Higher Education” (grant REC 007)
e-mail: rafael.cherkasov@ksu.ru
35

O-26
INVESTIGATING THE SYNTHETIC POTENTIAL OF
AMINOALKYLFERROCENYLDICHLOROPHOSPHANES
S. Tschirschwitz, P. Lönnecke, E. Hey-Hawkins *
Universität Leipzig, Institut für Anorganische Chemie, Johannisallee 29, D-04103 Leipzig, Germany;
tschirschwitz@chemie.uni-leipzig.de
A series of novel racemic as well as optically pure aminoalkylferrocenyl -dichlorophosphanes has
been prepared through the reaction of phosphorus trichloride with the corresponding
aminoalkylferrocene precursors. These compounds have proven to be versatile starting materials for
several syntheses. The chloro groups can be substituted subsequently and stereoselectivly leading to
diastereomerically pure P-chiral phosphanes which are promising ligands for catalytically active
complexes in homogeneous catalysis. A rather unusual substituent at the phosphorus atom is an
ortho-carbaboranyl group. It could easily be introduced stereoselectively via the reaction of a
monolithiated carbaborane with an aminoalkylferrocenyldichlorophosphane (Figure 1). The
remaining chloro group can also be substituted, for example by alkoxides.
Fig. 1
The aminoalkylferrocenyldichlorophosphanes can be converted into the corresponding primary
phosphanes, which can then be lithiated twice. The generated dilithium phosphanediides crystallise
from THF/hexane as Li12P6 cluster compounds that can be described as closo clusters according to
Wade’s rules.
36

O-27
SYNTHESIS AND REDOX PROPERTIES OF CROWDED DIPHOSPHINES:
APPROACHES TOWARD PHOSPHORUS-PHOSPHORUS INTER-VALENCE CHARGE
TRANSFER SYSTEMS
Shigeru Sasaki, Masatoshi Izawa, Kohji Sasaki, Kiyotoshi Kato, Midori Murakami, Fumiki Murakami, Masaaki
Yoshifuji, and Noboru Morita
Department of Chemistry, Graduate School of Science, Tohoku University, Aoba, Sendai 980-8578, Japan. E-mail:
sasaki@mail.tains.tohoku.ac.jp
Crowded triarylphosphines such as 1 1 have large bond angles around the
phosphorus and are oxidized at low potentials to stable cation radicals. We
synthesized crowded triarylphosphines carrying functional sites such as donors and
acceptors and investigated redox properties andintramolecular interaction between
the phosphorus and the functional sites. 2 Diphosphines carrying crowded
triarylphosphine structures are expected to be two-step redox systems and cation radicals can be
mixed valence or inter-valence charge transfer systems depending on the spacer. We herein report
synthesis and redox properties of crowded diphosphines such as 2 2a and 3.
Analogous nitrogen compounds such as TPD are applied to hole injecting and transporting
materials of electro-optic devices and studied as organic mixed-valence systems.
Crowded diphosphines were synthesized from common key intermediates,
(bromoaryl)phosphines, and redox properties were studied by cyclic voltammetry, EPR, and
UV-Vis-NIR spectroscopies. Diphosphines exhibit reversible two-step redox waves suggesting
formation of stable cation radicals. Detailed study on the oxidation will be presented.
References
[1] Sasaki, S.; Sutoh, K.; Murakami, F.; Yoshifuji, M. J. Am. Chem. Soc. 2002, 124, 14830-14831.
[2] a) Sasaki, S.; Murakami, F.; Murakami, M.; Watanabe, M.; Kato, K.; Sutoh, K.; Yoshifuji, M. J. Organomet.
Chem. 2005, 690, 2664–2672. b) Sutoh, K.; Sasaki, S.; Yoshifuji, M. Inorg. Chem. 2006, 45, 992–998. c) Sasaki, S;
Murakami, F.; Yoshifuji, M. Organometallics 2006, 25, 140–147.
37

O-28
THE ORGANOPHOSPHORUS SULFENYL BROMIDES AS VERSATILE REAGENTS
FOR CYSTEINE DERIVATIVES FUNCTIONALIZATION BY UNSYMMETRICAL
DISULFIDE BOND FORMATION
Mateusz Szymelfejnik, Sebastian Demkowicz, Dariusz Witt, and Janusz Rachon
Department of Organic Chemistry, Chemical Faculty, Gdansk University of Technology, Narutowicza 11/12, Gdansk,
Poland, 80-952. Fax: +48 58 347 2694,
E-mail: rachon@chem.pg.gda.pl
Disulfides are important compounds for both chemical and biological processes. There are many
biologically active peptides and peptide mimetics possess unsymmetrical disulfide bonds.
Disulfides are applied for preparation of self-assembled monolayers (SAMs) and
monolayer-protected clusters (MPCs) with the interesting properties.
The most widely used method of unsymmetrical disulfides formation involves the thioalkylation
of a thiol by derivatives of N-sulfenylphthalimide, N-sulfenamides, (from diethyl azodicarboxylate
DEAD), sulfenyl chlorides, Bunte salts, and 2-pyridyldisulfide (obtained from Aldrithiol). Thiolysis
is favored for the synthesis of unsymmetrical disulfides by above methods, although yields may be
compromised by required long time and rapid thiol-disulfide exchange reactions.
Here, we present a new and versatile synthesis of unsymmetrical disulfides based on the readily
available 5,5-dimethyl-2-thiono-1,3,2-dioxaphosphorinanyl sulfenyl bromide 2 from treatment of
bis-(5,5-dimethyl-2-thiono-1,3,2-dioxaphosphorinanyl) disulfide 1 with bromine at 0℃ The
developed procedure is very rapid (15 min) and proceeds under mild conditions and excellent yields
(90-100%). Cysteine derivatives functionalized at sulfur by unsymmetrical disulfide bond can be
prepared from thiols bearing neutral, aromatic, basic or acidic functionalities with variable length of
carbon chain.
The success of the method depends on the selective reactivity of
5,5-dimethyl-2-thiono-1,3,2-dioxophosphorinanyl-2-disulf nyl derivatives 3 toward protected Cysteine
to afford exclusively unsymmetrical disulfides 4. The observed selectivity emerged from excellent
leaving group property for dithiophosphate anion (pK 2 for corresponding acid). This property is
a
crucial for the short times required for the transformation and minimizes further disulfide exchange
between product 4 and used Cysteine derivative.
In conclusion, a convenient, versatile, functionalization method of Cysteine derivatives by
unsymmetrical disulfide bond formation has been developed. Simple procedure combined with
excellent yields make this method an attractive alternative to other reported procedures.
38

O-29
AMBIDENT ELECTROPHILICITY OF 5-MEMBERED RING PHOSPHATE TRIESTERS
Nissan Ashkenazi,* a Yoffi Segall, a Yishai Karton, a
Sanjio S. Zade b and Michael Bendikov b
a
Department of Organic Chemistry, IIBR-Israel Institute for Biological Research, P.O.Box 19, Ness-Ziona 74100, Israel.
b Department of Organic Chemistry, Weizmann Institute of Science, Rehovot 76100, Israel
Reactions of 2-ethoxy-1,3,2-dioxophospholane 2-oxide (ethyl ethylene phosphate) with various
hard and soft nucleophiles exhibited that this cyclic phosphate triester features ambident
electrophilicity. In general, harder nucleophiles attack on the P center to form the P-O bond
cleavage products, while softer nucleophiles attack on the ring carbon to yield the C-O bond fission
products. Exception to this generality can be found when bulky hard nucleophiles attack on the ring
carbon. In contrast to all other carbanions, which were checked, benzylmagnesium chloride yields
exclusively the C-O bond fission product, probably via a more complexed mechanism.
Ab intio and DFT calculations shed more light on the selectivity of C-O vs. P-O cleavage,
showing that the reactions of 2-alkoxy-1,3,2-dioxophospholane 2-oxide with various nucleophiles
are kinetically controlled, although C-O scission is always the thermodynamically preferred
process.
As no exocyclic bond was cleaved, we may suggest that the 5-memebered ring enhances the
reactivity of not only the P atom, but also of the ring carbon.
EtO
O
P
O
O -
Y
Y -
EtO
O
P
O
39
O
X -
EtO
O
O
P
X
Y= Bn, O-t-Bu, SPh, SEt, PPh 2.
X= H, Me, Et, i-Pr, sec-Bu, cyclopropyl, cyclopentyl, cyclohexyl, Ph, ethynyl, allyl.
O -

O-30
A NEW APPROACH TO THE SYNTHESIS OF PHOSPHORANES ON THE BASIS OF
THE REACTION OF BENZO[D]-1,3,2-DIOXAPHOSPHOLES, HAVING Β- OR
Γ-UNSATURATED GROUP IN SUBSTITUENT, WITH COMPOUNDS CONTAINING
MULTIPLE BONDS
V.F.Mironov 1,2 , L.M.Burnaeva 1 , L.M.Abdrakhmanova 2 , M.N.Dimukhametov 2 ,
Yu.yu. Kotorova 1 , I.V.Konovalova 1
1 Kazan State University, Kremlevskaya Str. 18, Kazan, 420008 Russia
2 A.E.Arbuzov Institute of Organic and Physical Chemistry, Russian Academy of Sciences,
Arbuzov Str. 8, Kazan, 420088, Russia, e-mail: mironov@iopc.knc.ru
It is known that the Р(III) derivatives, containing such a group as NCO, NCS, C≡CR, RC=CR2
bonded with phosphorus, easily react with carbonyl compounds to give various P-heterocycles. The
formation of the intermediate P–C–O – or P–O–C – bipolar ions and the intramolecular attack of
anionic moiety on unsaturated substituent at phosphorus are postulated in these reactions and lead to
the final P-heterocycles. Here we attempted to extend this approach to the relatively stable Р(III)
derivatives (1a-d), containing a substituent not bonded directly with phosphorus. The various types
of phosphoranes (3, 4) were obtained with high regio- and stereoselectivity. The possible pathways
of its formation and crystal structures are discussed. The work is supported by MK-1434.2006.3
program.
O Ph
P O
O
O
O R1
P
O
CF3
O CF3
CCl3CHO, (CF3)2C=O, ArCH=C(COOR)2, ROOCC CCOOR and etc.
Ph
1
O
P O
O
PhCH=N
1a
O
O
or (and) P
X X Z
2
Y Z
Y
3
4
E, Z
1b 1c 1d
P
O P
X=Y
+ C Z
O R
P O
O R
O
O
O
P*
O
CF3
N
* CF3 O
Ph
O O
P
O
Ph
O O
P
O
*
*
O
* Ph
O
CF3 CF3
Me
*
O
*
CF3
O Me
CF3
Me
* O
O
CCl3
O P
*
O
O
*
3a
3d
3b
O Ph
P
* O
* CCl3
* O
O
CF3 CF3 4a
3c
O Ph
*
P O CF3
* O CF3 O
CF3 CF3 4b
References
[1] Pudovik A.N. et al. Synthesis. 1986, (10), 793-804.
[ 2 ] Mironov V.F. et al. Uspekhi Khim. (Rus. Chem. Rev.). 1996, 65(11), 1013-1051.
40

O-31
DIASTEREOSELECTIVE SYNTHESIS OF ENANTIOPURE Α-AMINOPHOSPHONIC
ACIDS DERIVATIVES
Vladimir A. Alfonsov
A.E.Arbuzov Institute of Organic and Physical Chemistry, Kazan Scientific Centre of the Russian, Academy of
Sciences, 420088, Arbuzov Str., 8, Kazan, Russian Federation. Fax: +7 8432 75 5322. E-mail: alfonsov@iopc.knc.ru
This report is devoted to A.N. Pudovik (1915-2005).
The preparation of enantiopure organophosphorus compounds has been of great interest over the
last few years due to the opportunity to use them as chiral drugs and ligands for design of
homogeneous or heterogeneous catalysts. Rather attractive among these compounds are
α-aminophosphonic acids derivatives due to their well-known biological activity. One of the ways
to the α-aminophosphonic acids derivatives is Pudovik reaction. In this report the use of this
reaction in enantioselective synthesis of aminophosphonates is shortly shown and our own
investigations in this field will be delivered. We have found several new and efficient ways of the
synthesis of cyclic and acyclic aminophosphonic acids derivatives by the reaction of trivalent
phosphorus compounds with β-aldiminoalcohols and iminocarbonic acids. In the case of chiral
initial compounds most of these reactions proceed diastereoselectively that permits to obtain final
products with very high diastereo- and enantiopurity. The essential way for increasing
stereoselectivity of such reactions is the use of cyclisation as stereocontrolling steps.
This work was supported by the Civilian Research and Development Foundation (grant no. RUC2-2638-KA-05) and
the Russian Foundation for Basic Research (grant no. 03-03-33082).
41

O-32
PHOSPHORYLATION OF IMINO ANALOGS OF Α-HALOCARBONYL COMPOUNDS
Yuliya V. Rassukana, Petro P. Onys’ko, Anatoly D. Sinitsa
Institute of Organic Chemistry, NAS of Ukraine, 02094 Kyiv, 5 Murmans’ka St.
E-mail: onysko@rambler.ru
The chemoselectivity of reactions between α-haloimines – compounds containing Hal-C-C=Nskeleton
– and nucleophilic phosphorus derivatives are discussed systematically. The synthetic
potentialities as well as possible mechanistic pathways of this currently developing field of
organophosphorus chemistry are considered. Phosphorylation of the α-haloimines leads mainly to
C- or N-phosphorylated compounds as the final products, the selectivity being dependent on the
type of halogen, substituents at the imine carbon and nitrogen atoms, and on the nature of
phosphorus reagent.
SO 2 R'
N PR 3
E A
R Hal
R'
R Hal E A
N
O
P(OR) 3
E A
R Hal
R Hal
X
N
N P
R R
E A
O
R Hal N X
PR 2
O
E A =R 2 PO
N
42
X
Hal
Hal
O
PR 2
E A
R Hal
P(O)R' 2
N X
P(O)R 2
The main factors controlling regio- and stereoselectivity are elucidated. A series of novel
theoretically and preparatively important transformations are found out, i.e., new diad
rearrangements involving the N→C and C→N transfer of a sulfonyl or a phosphoryl group, the
unusual acylation of the electrophilic imine carbon atom by tervalent phosphorus isocyanates, and
others. Variety of transformations is connected with possible participation in reactions of C=N bond,
halogen atoms or N-substituents. The use of haloimines as versatile building blocks for synthesis of
practically promising functionalized aminophosphonates, bisphosphonates, phosphorus analogs of
dehydro aminoacids, etc., is demonstrated.
N
H
X

O-105
HIGHLY STEREOSELECTIVE AND STEREOSPECIFIC EPOXIDATION OF
2-PHOSPHOLENES AND N-GLYCOSIDES OF PHOSPHA SUGARS AND THEIR
BIOASSAYS
Mitsuji Yamashita, 1* Taishi Niimi, 1 Michio Fujie, 1,2 Valluru Krishna Reddy, 1 Hirono Totsuka, 1 Buchammagari
Haritha, 1 Maddali Kasthuraiah Reddy, 1 Satoki Nakamura, 2 Kazuhide Asai, 3 Takuya Suyama, 1 Gang Yu, 1 Masaki
Takahashi, 3 and Tatsuo Oshikawa 4
1
Department of Nano Materials, Graduate School of Science and Technology, Shizuoka University, Hamamatsu 432-8561, Japan
2
Faculty of Medicine, Hamamatsu University School of Medicine, Hamamatsu 431-3192, Japan
3
Department of Materials Chemistry and Chemical Engineering, Faculty of Engineering, Shizuoka University, Hamamatsu 432-8561,
Japan
4
Department of Materials Chemistry and Biochemistry, Numazu College of Technology, Numazu 410-8501, Japan
tcmyama@ipc.shizuoka.ac.jp
Phospha sugar derivatives are pseudo sugar analogues having a phosphorus atom in the sugar
ring structure represented by Haworth equation. Normal sugars have an oxygen atom in the
hemiacetal ring, and the popular pseudo sugars have a carbon, nitrogen, or sulphur atom, which are
naturally occuring and are called as carba, aza, or thia sugars. These popular pseudo sugars are
well investigated and many of them are known to be biologically active materials. On the other
hand, phospha sugars are not yet found in the nature and the synthesis and characterization of them
are not so well studied.
Previous methodologies for the preparation of phospha sugars used entirely sugar starting
materials, however, we are challenging to develop novel synthetic routes from phosphorus
heterocyclic compounds, mainly, 2- or 3-phospholene derivatives. Here we will report a new
reaction to prepare 2,3-epoxyphospholanes by stereoselective and stereospecific epoxidation of
2-phospholenes with sodium peroxide (1,2) and the reaction of the epoxides with nucleophiles such
as amines for the preparation of N-glycosides of phospha sugar derivatives as well as their
bioassays.
Treatment of 1-phenyl-2-phospholene 1-oxide (1) with sodium peroxide gave erythro
2,3-epoxy-1-phenylphospholane 1-oxide (2) in highly stereoselective and stereospecific manner.
Epoxide 2 as well as the diastereomeric threo epoxide prepared separately by epoxidation with
hydrogen peroxide or via addition reaction of bromine in aqueous medium was converted into
2-amino-3-hydroxy-1-phenylphospholane 1-oxide (3) by the reaction of amines with inversion of
the stereochemistry. Amino derivatives 3 are N-glycosides of phospha sugar derivatives, therefore,
the present epoxide preparation may be an important finding for the phospha sugar chemistry.
Some of phospha sugars and phospholanes prepared were subjected to bioassay to show very
important characters for medicines.
Ph
P
O
Na 2 O 2
Ph
P
O
1 eryhthro 2 threo 3
Reference
[1] Yamashita, M.; Valluru, K. Reddy; Lakonda, N. Rao; Buchammagari, H.; Maeda, M.; Suzuki, K.; Totsuka, H.;
Takahashi,M.; Oshikawa, T. Tetrahedron Lett. 2003, 44, 2339-2341.
[2] Totsuka, H.; Maeda, M.; Valluru, K. Reddy; Takahashi, M.; Yamashita, M. Heterocyclic Commun. 2004, 10,
295-300.
O
43
NHRR'
Ph
P
O
OH
NRR'

O-106
CHIRAL P-HETEROCYCLES: EFFICIENT METHOD FOR THE OPTICAL
RESOLUTION OF 3-METHYL-3-PHOSPHOLENE 1-OXIDES
Tibor Novák, 1 József Schindler, 1 Viktória Ujj, 2 János Deme, 2 Ádám Bódis, 2
Elemér Fogassy 2 and György Keglevich 2
1
Research Group of the Hungarian Academy of Sciences at the Department of Organic Chemical Technology, Budapest
University of Technology and Economics, H-1521 Budapest, Hungary
2
Department of Organic Chemical Technology, Budapest University of Technology and Economics, H-1521 Budapest,
Hungary
The few methods described in the literature on the resolution of phosphorus compounds are based
mainly on the formation of separable diastereomeric salts. A practical procedure for the
enantiomeric resolution of 1-substituted-3-methyl-3-phospholene 1-oxides (1) by separation of the
diastereomeric associations (1·2) formed by interaction with chiral hosts, such as TADDOL
derivatives (2) is described.
P
O Y
1
Y = aryl, alkyl, alkoxy
Ph
Ph
R 1
O
OH
2
44
R 1
O
HO
Ph
Ph
R 1 = Me,
R 1 = Me,
The antipodes of 1-aryl-, 1-alkyl- and 1-alkoxy-3-methyl-3-phospholene 1-oxides (1) were
separated in good yields and in most cases in high enantiomeric excess. The novel procedure seems
to be of general value, as can be applied for the resolution of chiral phosphine oxides and
phosphinates.
Y Ph o-Me-Ph p-Me-Ph Naphthyl Et Pr EtO
enantiomeric
excess [%]
>99 >99 >99 >99 60 95 95

O-107
AIR-STABLE CHIRAL PRIMARY PHOSPHINES
L. J. Higham † , R. M. Hiney ‡ and D. G. Gilheany ‡
† School of Natural Sciences-Chemistry, Bedson Building, University of Newcastle, Newcastle-upon-Tyne, NE1 7RU
‡ School of Chemistry and Chemical Biology, University College Dublin, Belfield, Dublin 4, Ireland
Compounds of phosphorus in the +3 oxidation state have been shown to be incredibly useful and
versatile molecules with medicinal, electronic and catalytic applications. 1 They are used to make
products as diverse as (-)-menthol 2 (the mint flavouring in many foodstuffs) and L-Dopa, a potent
anti-Alzheimer's drug. 3
One potential route to building current and advanced types of these molecules would be to
convert phosphorus hydrogen bonds into other - for instance carbon - bonds using primary
phosphines - RPH2, which possess two such PH bonds. This approach is generally ignored due to
the fearsome reputation of low molecular weight primary phosphines as being molecules that are
spontaneously flammable, occasionally explosive and often toxic. For applications like preparing
chiral pharmaceuticals using catalysis (e.g. L-Dopa) we also need to build in chirality somehow.
In this work we present our discovery 4 of a new class of air-stable, chiral primary phosphine
(CPP), which presents a gateway to many types of phosphorus-containing molecule. We discuss the
origin of their stability, which is unlikely to be due to sterics and is not due to the presence of a
stabilising heteroatom (the only known stabilising forces for RPH2). So what is this stabilising
factor? We also show the first crystal structure of one of our CPPs - the first example of a CPP to be
characterised in this way. The discovery of a chiral molecular framework that stabilises the PH
bond suggests these phosphines will be of significant value as chiral precursors to a whole host of
new ligands in homogeneous catalysis. This will be demonstrated by presenting very recent work
describing novel ligands we have synthesised and preliminary results in catalytic transformations.
Reference
1. K. V. Katti, N. Pillarsetty, K. Raghuraman, Top. Curr. Chem. 2003, 229, 121-141.
2. K. Tani, S. Otsuka et al. J. Am. Chem. Soc. 1984, 106, 5208-5217.
3. W. S. Knowles, Acc. Chem. Res. 1983, 16, 106-112.
4. R. M. Hiney, L. J. Higham, H. Müller-Bunz, D. G. Gilheany, Angew. Chem. Int. Ed. 2006, 45, 7248-7251.
45

P-1
α-IMINOTRIFLUOROETHYL PHOSPHONATE – THE FIRST REPRESENTATIVE OF
C-PHOSPHORYLATED N-H IMINES
A. D. Sinitsa, M. V. Kolotylo, Yu. V. Rassukana, V.V. Pirozhenko and P. P. Onys’ko,
Institute of Organic Chemistry, NAS of Ukraine, 02094 Kyiv, 5 Murmans’ka St.
E-mail: onysko@rambler.ru
The convenient approach to imine 1 – the first representative of previously unknown N-H
iminoalkyphosphonic acid derivatives was elaborated.
CF 3 CN
(EtO) 2 P(O)H
:B
46
O
F 3 C
P(OEt) 2
It is noteworthy that trichloroacetonitrile, CCl3CN, under similar reaction conditions acts as
chlorinating agent, to give mainly chlorophosphate (EtO)2P(O)Cl.
With a few exceptions, N-H imines have been reported as unstable compounds, leading to
difficulties in their isolation 1 . Phosphorylated N-H imine 1 is quite stable at ordinary conditions and
exists as Z/E mixture of stereoisomers; Z isomer: δP –1.4 ppm, 3 JHP 37.2 Hz, δF –69.7 ppm, 3 JFP 1.9
Hz, 4 JFH 1.2 Hz; E isomer: δP –0.7 ppm, 3 JHP 58.2 Hz, δF –72.4 ppm, 3 JFP 1.9 Hz, 4 JFH 0.6 Hz (Z/E =
10:1). Obviously Z-isomer is stabilized by intramolecular P=O…H-bonding. Imidoyl phosphonate
1 can be readily functionalized. In particular, it adds phosphorus-, oxygen- or sulfur-centered
nucleophiles allowing preparation of bisphosphonates or phosphorylated thiazolidones.
F 3 C
O
O
F 3 C
P(OEt) 2
OR
P(OEt) 2
NH 2
NH 2
[H]
ROH
O
F 3 C
P(OEt) 2
N H
1
(RO) 2 P(O)H
1
N H
O
F C 3 O
HSCH 2 CO 2 H
O
S
P(OEt) 2
NH2 N
H
P(OR) 2
O
P(OEt) 2
Reference
[1] F. Gosselin, P.D.O’Shea, S. Roy, R.A. Reamer, Cheng-yi Chen, R.P. Volante., Org. Lett. 2005, 7, 355.
CF 3

P-2
SYNTHESIS OF CALIX[4]RESORCINS, CONTAINING PHOSPHORYL FRAGMENTS
ON THE BOTTOM RIM OF THE MOLECULE
A. R. Burilov, I. R. Kniazeva, Yu. M. Sadykova, M. A. Pudovik, W.D. Habicher, I. Baier, A. I. Konovalov
A.E.Arbuzov Institute of Organic and Physical Chemistry, Kazan Scientific Centre of the Russian Academy of
Sciences, Arbuzov Str., 8, 420088 Kazan, Russian Federation. Fax: +7 8432 75 5322; Email: pudovik@iopc.knc.ru
Two synthesis methods for calyx[4]resorcins bearing phosphonate groups on the bottom rim of
the molecule were developed. First of them consists of the interaction of phosphorylated acetals
1a-e with resorcin. The reactions were carried out in acid medium to give calixarenes 2a-e
containing dialkoxyphosphoryl fragments. These compounds when isolated are easily hydrolyzed to
calixarenes 3a-e with the elimination of one of the alkoxy groups of the phosphonate fragment. The
compounds 3a-e were isolated and characterized.
4 (RO) 2P(O)CH 2CH(OEt) 2
1a-e
HO OH
+
H
+ 4
-8 EtOH
O
R = Et (a), Pr (b), i-Pr (c), Bu (d); i-Bu (e)
47
HO
CH
CH2 P(OR) 2
OH
+
H (H 2O)
4
-4 ROH
HO
CH
CH 2
O P OR
OH
The second approach is based on the introduction of etoxyvinylphosphonates to the reaction with
resorcin. The interaction of etoxyvinyldichlorophosphonate with resorcin allows one to obtain water
soluble calix[4]resorcine 4, containing four acidic phosphonic fragments on the bottom rim of
calixarene matrix. The use of ethers of ethoxyvinylphosphonic acid in the reaction with resorcin
resulted in the formation of calixarenes 3a-e. The stability of the obtained calixarenes increases
with the increase of alkyl radical length in initial phosphonate. For example, calixarenes with
(С7Н15O)2P(O) or (С12Р25O)2P(O) fragments reveal hydrolytic stability.
4 EtOCH=CHP(O)Cl 2
+
HO
4
OH
HCl
-4 EtOH
R = CH2P(OH)2
2a-e
R R
This study was supported by the Russian Foundation for Basic Research (grant no. 05-03-32136).
O
HO
HO
HO
HO
R
4
R
OH
OH
OH
OH
3a-e
OH
4

P-4
INTERACTION OF 3-ALKYL-2-ALKOXY-1,3,2-OXAZAPHOSPHINANES WITH
ALKYLCHLOROFORMATES
A.E. Shipov, G.K. Genkina, P.V. Petrovskii, T.A. Mastryukova
A.N. Nesmeyanov Institute of Organoelement Compounds RAS, 28 ul. Vavilova, 119991 Moscow, Russian Federation.
E-mail: shipov@ineos.ac.ru
1,3,2-Oxazaphosphinane analogues of phosphoryl formic acid derivatives could be of interest as
biologically active compounds. In this connection the reaction of phosphinanes (1) with alkyl
chloroformates (2) was investigated.
NR 1
P
O
1
OR 2
+
ClCOOR 3
2
R 1 = Pr i
R 1 = Me, Bu, Ph
48
NR 1
3
O
P
O
3
+
COOR 3
4
+
+
NR 1
Cl
4
P
NR
P 2
OR
O
5
1
COOR 3
Cl
OR 2
O
COOR 3
In contrast to the interaction of phosphinanes 1 with haloacetic acid derivatives the reaction
pathway of esters 1 with chloroformates (reaction products and their yields ratio) drastically
depends not only on the structure of the substituents R 2 in ester group but also on the structure of
the substituent R 1 at the nitrogen atom. When R 1 = i-Pr the reaction was found to proceed only with
the formation of two main products of the Arbuzov rearrangement – without (3) and with (4)
opening of the cycle, and yields ratios depended noticeably on the structure of R 2 (according to
NMR 31 P data 3 and 4 ratios are from 94 : 6 for R 2 = Me to 24.5 : 75.5 for R 2 = i-Pr). But when R 1 =
Me, Bu or Ph along with the Arbuzov reaction products 3 and 4 the formation of acyclic
chlorophosphite (5) takes place, besides when R 1 is Me and Ph chlorophosphite 5 becames the main
product of the reaction (the ratio of 5 to 3+4 is 72 : 28) and for R 1 = Bu this ratio is 15 : 85. The
yields ratio between 5 and 3+4 was found to depend also on the polarity of the solvent and
temperature of the reaction. As we suppose the main factor determining the reaction pathway and
yields ratio of products is the steric hindrances at the nitrogen atom. The structure of
chlorophosphites 5 was confirmed by the conversion (without isolation) into phosphorothioates or
phosphoroamidothioates.
Supported by the Russian Foundation for Basic Research (grant No. 05-03-33091).
References
A.E. Shipov, G.K. Genkina, P.V. Petrovskii, T.A. Mastryukova, Russ. Chem. Bull. Int. Ed., 2004, 53, 1996.

P-6
2,2,2-TRIBROMONAPHTHO[2,3-d]-1,3,2-DIOXAPHOSPHOLE: OBTAINING AND
REACTION WITH PHENYLACETYLENE
A.V.Bogdanov, V.F.Мironov, B.I.Buzykin, A.B.Dobrynin, D.B.Krivolapov, А.I.Konovalov
A.E.Arbuzov Institute of Organic and Physical Chemistry, Russian Academy of Sciences, Arbuzov Str. 8, Kazan,
420088, Russia, e-mail: mironov@iopc.knc.ru
The interaction of 2,2,2-trichlorobenzo-1,3,2-dioxaphosphole with arylacetylenes is a versatile
approach to the synthesis of benzo[e]-1,2-oxaphosphorinine derivatives – P-analogues of
biologically important coumarines [1]. Here we report the obtaining of
2,2,2-tribromonaphtho[2,3-d]-1,3,2-dioxaphosphole (1) from 1,2-naphthalenediol, PBr3 and
bromine and its reactions with phenylacetylene. The reaction of phosphole (1) with phenylacetylene
proceeds in several directions (10-15°C).
1
O
PBr3
O
Ph C CH
1
-PBr3, -Br2
1) Ph C
2) H2O
CH
6
OH
O
OH
O P
OH
The first and second pathways include the
formation of heterocycles (2) (2-3 %) and (3)
(20-23 %) after reaction mixture hydrolysis. The
third pathway is the disproportionation of
phosphole (1) with the following bromination
resulting in the formation of phosphoranes (4, 5).
The phosphates (6, 7) were obtained as a result of
hydrolysis. We succeeded in isolation of compound
(3, 7). Phosphate (6) was obtained by the
independent synthesis also. The structure of
2-phenyl-9-(2-dihydroxy
phosphoryl-1-phenylethen-1-yl)naphtho[1,2-d]furane
(3) was confirmed by single crystal X-ray
diffraction. The geometry of molecule (3) (solvate
with DМSО) in crystal is shown in the figure.
49
O O
P
OH +
7
Br
Ph
2 Ph
3 Ph
O
PBr
O 2
Br2
-HBr
O
PBr
O 2
4
5 Br
H2O -HBr
H2O -HBr
S
O
C
C
O 2
O 4
O
OH
O
OH
O P
OH
H
O
P
OH
OH
C2 C3 O1 C4 C5 C6 C8 C7 C23 C9 C12 P1 C10 O3 C11 C13 C16 C
H
15
C18 C14 C17 C22 C
H
3a
C1a C7a C7b H
C 21
C 20
C 19

P-7
SYNTHESIS, CHARACTERIZATION AND APPLICATIONS OF NOVEL
IMINOPHOSPHINITES
Jake Yorke, Sarah K. D. Beaton and Aibing Xia*
Department of Chemistry, Mount Saint Vincent University, Halifax, Nova Scotia, Canada
Unsymmetrical ligands with two or more different donors such as phosphorus and nitrogen
donors (P,N type) have attracted increasing attention due to their bonding versatility and catalytic
applications. We will report the synthesis, characterization and applications of two series of novel
bidentate and potentially hemilabile iminophosphinites, which can be prepared from readily
available starting materials such as aminophenols (Scheme 1) and salicylaldehydes (Scheme 2).
Initial results in Suzuki coupling reactions showed that palladium complexes based on both
iminophosphinites are active catalysts for deactivated bromides such as 4-bromoanisole. The
efficiency of series 2 iminophosphinites is generally better than that of series 1 iminophophinites
under similar conditions.
R
R
R
R
OH
R'2C=O NH 2
R
R
50
R'
OH
R''2PCl DMAP
N R
Scheme 1. Iminophosphinites (1) from aminophenols
OH
R'NH2 O
R
R
2
OH
C
N
R'
R' 2PCl
DMAP
Scheme 2. Iminophosphinites (2) from salicylaldehydes
Submitted by Aibing Xia, Department of Chemistry, Mount Saint Vincent University, Halifax, Nova Scotia, Canada
B3M 2J6
R'
R
R
1
R
R'
2
O
N
C
R'
O
PR'' 2
PR'' 2
N
R'

P-9
SYNTHESIS AND REACTIONS OF PHOSPHAISOCOUMARINS
Ai-Yun Peng*, Bo Wang, Xun Yang
School of Chemistry & Chemical Engineering, Sun Yat-sen University, 135 Xingangxi Lu, Guangzhou, 510275, China
Isocoumarins are a class of naturally occurring lactones that display diverse bioactivities, some
antitumor isocoumarins have especially gained considerable research interests. In contrast, related
reports about their analogues are rare. Since there is a remarkable similarity in bioactivities between
the carbon species and their phosphorus counterparts, one would anticipate that phosphorus
isocoumarin analogs (i.e. phosphaisocoumarins) might have potential bioactivities similar to those
of isocoumarins reported herein. Here we report the results on the synthesis of
phosphaisocoumarins and the investigations of their reactions with acetylene, alkene and Me3SiBr
(Scheme 1).
R 1
R 1
R 1
P(OEt) 2
O
I2,CHCl3 X
P O
O OEt
X = I, Br, Cl
O
R
2 R R2
R 2
R 2
P O
OEt
O
O
1 R P
R P
EtO OH
O OEt
1
NaOH CuI
DMF
NXS, DMF
Pd (II)
R 1
Me 3SiBr
R 1
O
51
R 3
R 2
P O
OEt
O
R
P O
OH
or
R 2
R 1
O
R 2
R 4
R 2
P O
OEt
Scheme 1
These novel synthetic phosphorus heterocycles have showed medium inhibitory activity to
protein tyrosine phosphatase 1B (PTP1B) and good cytotoxicity against the human cancer cells
HepG2 and BGC through the in vitro bioactivity experiments.
Reference
[1] Powers, J. C.; Asgian, J. L.; Ekici, Ö. D.; James, K. E. Chem. Rev. 2002, 102, 4639-4750, and references therein.
[2] Quin, L. D.; A Guidorus Chemistry, e to Organophosph John Wiley & Sons, Inc., New York, 2000, Chapter 11.
[3] Ai-Yun Peng, Yi-Xiang Ding. J. Am. Chem. Soc. 2003, 125, 15006-15007.
[4] Peng, A. –Y.; Ding, Y.-X. Org. Lett. 2004, 6, 1119-1121.
[5] Ai-Yun Peng, Yi-Xiang Ding. Tetrahedran 2005, 61, 10303- 10308.

P-14
NUCLEOPHILIC PHOSPHINE-CATALYZED [3+2] CYCLOADDITION OF
ALLENES WITH N-(THIO)PHOSPHORYL IMINES: FACILE SYNTHESIS
OF SUBSTITUTED 3-PYRROLINES
Bo Zhang, Zhengjie He *
The State Key Laboratory of Elemento-Organic Chemistry, and Department of Chemistry, Nankai University, Tianjin
300071, China
In recent years, carbon-carbon bond-forming reactions catalyzed by nucleophilic phosphine have
attracted much attention1,2. One of these kinds of reactions is the cycloaddition reaction of allenes
with imines, forming 4-, 5-, or 6-membered N-heterocycles3. Due to the importance of these
N-heterocyclic compounds in the organic synthesis and pharmaceuticals, the relating reaction has
been extensively studied. Aryl substituted N-tosyl imine compounds were most commonly used for
the reaction for their better reactivity, giving N-tosyl heterocycle products. However, since tosyl
group is not easy to be removed under mild conditions, therefore in most cases, products have been
reported as N-tosylated ones. Few attempts were successful in giving corresponding deprotected
N-heterocycles but other new products, even if much easy-removed sulfonyl groups like Nosyl and
2-trimethylsilylethanesulfonyl were used3c.
As part of our research on nucleophilic phosphine-catalyzed carbon-carbon bond-forming
reactions4, we herein report the preliminary results on the cycloaddition reaction of allenes with
N-(thio)phosphorylated imines. The cycloaddition reaction was catalyzed by an air stable
trialkylphosphine PTA (1,3,5-triaza-7-phosphaadmantane), and afforded [3 + 2] cycloaddition
products N-(thio)phosphoryl 3-pyrrolines with good yields, which were smoothly deprotected
through HCl-mediated acidic methanolysis to 3-pyrrolines. Thus, a facile synthesis for substituted
3-pyrrolines is established.
R 1
+ N
EWG
R2 P PTA
P
N R
EWG
2
R1 52
HCl
CH 3OH
R 1
H
N
R 2
EWG
R 1 = Alkyl, H, Phenyl; R 2 = Aryl; P = P(S)(OEt) 2, P(S)Ph 2, P(O)(OEt) 2; EWG = CO 2Et
Acknowledgment: The authors gratefully acknowledge financial support for this study from the National Natural
Science Foundation of China (Grant No. 20421202; 20672057).
References
1. X. Lu, C. Zhang, Z. Xu, Acc. Chem. Res. 2001, 34, 535-544.
2. J. L. Methot, W. R. Roush, Adv. Synth. Catal. 2004, 346, 1035-1050.
3. For recent examples, see: a) X.-F. Zhu, J. Lan, O. Kwon, J. Am. Chem. Soc. 2003, 125, 4716-4717; b) G.-L. Zhao,
4. M. Shi, J. Org. Chem. 2005, 70, 9975-9984; c) X.-F. Zhu, C. E. Henry, O. Kwon, Tetrahedron 2005, 61,
6276-6282.
5. Z. He, X. Tang, Y. Chen, Z. He, Adv. Synth. Catal. 2006, 348, 413-417.

P-17
DISELENOPHOSPHATES: SYNTHESIS, REACTION WITH ELECTROPHILES,
AND P-Se BOND CLEAVAGE
Chen-Wei Liu
Department of Chemistry, National Dong Hwa University, Hualien 974, Taiwan
Fax: 886-3-8633570, E-mail: chenwei@mail.ndhu.edu.tw
Dialkyl diselenophosphates, Se2P(OR)2 - , abbreviated as dsep can be prepared in good yields by
reacting P2Se5 with various alcohols, and isolated as ammonium salts. The central phosphorus atom
adopts tetrahedral structure, proved by single crystal X-ray diffraction analysis. Se of dsep ligand, a
good nucleophile,which can react with acyl chloride to form (1), can also react with propargyl
bromide to form (2). Compound (3) (scheme 1) can be obtained by performing Michael addition
reaction using dsep ligand and but-3-en-2-one as reactants. Interestingly, a rare selenophosphito
moiety of iron, CpFe(CO)2P(Se)(OR)2 (4), was obtained by treatmenting dsep ligands with
[CpFe(CO)2]2 in refluxing toluene (scheme 2). The observed selenophosphito fragment in (4)
clearly suggests that P-Se bond cleavage can occur in the process of thermal reaction of
[CpFe(CO)2]2 with phosphor-1,1-diselenolates. The novel reagent, (4), finally exhibits not only
coordination properties at Se center by forming heterometallic clusters but also reactivity at Se-site
towards C-based electrophiles.
Scheme 1
Scheme 2
NH 4Se 2P(O i Pr) 2
OC
Fe
O
C
C
O
Fe
CO
O
CH2Cl2, N2, RT,8hr
CH3COCl CH2Cl2, N2, RT, 1hr
HC CCH2Br
CH 2Cl 2, N 2, RT,1hr
RO
+ P
RO
Se
Se
53
O
O
Se
P
Oi O
Pr
iPr (3)
Se
Se
Se
Se
P
Se
O i Pr
P
O i Pr
OiPr (2)
O i Pr
(1)
Toluene
Fe
110
OC
OC
o Se
(4)
C, 4 h P
OR
RO

P-23
TRICYCLES SYNTHESIZED BY THE REACTION OF PCl5 WITH
OPEN-CHAINED MOLECULES
Ferdinand Belaj
Institut für Chemie, Karl-Franzens-Universität Graz, Schubertstr. 1, Austria. E-mail: ferdinand.belaj@uni-graz.at
The tricyclic reaction products of PCl5 with two open-chained molecules containing C=O and
NH2 groups are characterized by single-crystal structure determinations: The reaction of oxamide
with PCl5 [1] resulted in the symmetric compound (I) formed by a ring closure reaction followed by
a [2+2] cycloaddition:
The reaction of glutamic acid with PCl5 takes a completely different course and the hitherto
unknown unsymmetric compound (II), a derivative of the dipeptide cyclo(prolyl-proline), was
formed repeatedly:
Obviously, no phosphorus atoms were incorporated in a ring closure reaction and PCl5 acts
mainly as a dehydrating agent. The crystal structure determinations were performed at low
temperature: Compound (I) has two half molecules in the asymmetric unit and shows almost planar
tricycles arranged around centers of symmetry. The molecules of compound (II) lie on general
positions.
Reference
[1] M. Becke-Goehring, Z. Anorg. Allg. Chem. 373: 245-257 (1970).
54

P-24
MONODENTATE SPIRO PHOSPHONITES: HIGHLY EFFICIENT LIGANDS FOR
ASYMMETRIC HYDROGENATION OF NON-ACYLATED ENAMINES
Guo-Hua Hou, Shou-Fei Zhu, Jian-Hua Xie, Qi-Lin Zhou*
State Key Laboratory and Institute of Elemento-organic Chemistry, Nankai University Tianjin 300071, China
In last few decades, the catalytic asymmetric hydrogenation of N-acylated enamines such as α-
and β-N-acylamino acrylates, and enamides have been extensively studied, providing a highly
enantioselective and convenient method for the synthesis of enantiomer-enriched primary and
secondary amine derivatives. However, only a limited progress has been achieved in the direct
preparation of chiral tertiary amines, which broadly occurred in biologically active molecules and
natural products, by asymmetric hydrogenation of the simple N,N-dialkylenamines. Recently, we
have synthesized a new type of phosphonite ligands containing a chiral 1,1′-spirobiindane scaffold.
In this presentation we will report their application in Rh-catalyzed asymmetric hydrogenation of
non-acylated enamines such as N,N-dialkylenamines, providing the corresponding chiral tertiary
amines in high yields and excellent enantioselectivities (up to 99.9% ee).
Ar 1
N
OH
HO
RPCl 2, Et 3N
THF, rt, 1h
(S)-SPINOL (S)-1
Ar 2
55
O
P
O
R
H2 (10 atm)
[Rh] (1 mol%) / (S)-1c (2.2 mol%)
I 2 (2 mol%), HOAc (20 mol%), THF, rt
a: R = Me
b: R = i Pr
c: R = t Bu
d: R = Ph
2 3 (up to 99.9% ee)
Acknowledgment: We thank the National Natural Science Foundation of China, and the Ministry of Education of China
for financial support.
References
(1) Lee, N. E.; Buchwald, S. L. J. Am. Chem. Soc. 1994, 116, 5985.
(2) Tararov, V. I.; Kadyrov, R.; Riermeier, T. H.; Holz, J.; Börner, A. Tetrahedron Lett. 2000, 41, 2351.
(3) Hou, G.-H.; Xie, J.-H.; Wang, L.-X.; Zhou, Q.-L. J. Am. Chem. Soc. 2006, 128, 11774.
Ar 1
N
*
Ar 2

P-25
MICROWAVE-ASSISTED SYNTHESIS IN ORGANOPHOSPHORUS CHEMISTRY
György Keglevich, Melinda Sipos, Anna Szekrényi, Eszter Dudás,
Daniella Takács and Emília Hohmann
Department of Organic Chemical Technology, Budapest University of Technology and Economics
H-1521 Budapest, Hungary
In the last decade, microwave (MW)-assisted accomplishment of syntheses has become
widespread. We made use of MW irradiation in organophosphorus chemistry. First, the
phospha-Mannich condensation of secondary amines, paraformaldehyde and >P(O)H species
including P-heterocycles to afford aminomethylene-P(O)< derivatives was studied under MW and
solventless conditions.
O
NH + (CH 2O) n + HP
56
MW
O
N CH 2 P
Only in a part of the phospha-Michael reaction studied by us was the MW technique useful.
The Diels-Alder cycloaddition of 1,2-dihydrophosphinine oxides with dienophiles was, however,
highly promoted by MW irradiation, again in a solvent-free accomplishment. The
2-phosphabicyclo[2.2.2]octene oxide derivatives were obtained in excellent yields.
Cl
Y
O
P
Me
CO 2Me
CO 2Me
CO 2Me
CO 2Me
MW
Cl
P
O Y
Me
Y= aryl, alkyl, alkoxy
O
O
MW
N Ph
Cl
Y
O
P
Et
H
O
H
N
O Ph
The inverse Wittig reaction of 1-trialkylphenyl cyclic phosphine oxides and dialkyl
acetylenedicarboxylate results in the formation of the corresponding β-oxophosphoranes. The novel
reaction is, however, rather slow as the completion requires 10 days at 150 °C. Application of MW
without the use of any solvent brought a real breakthrough, as there was a 80-fold acceleration
beside the much better efficiency. Moreover, aryl derivatives otherwise unreactive under traditional
heating could also be involved in the reaction under discussion.
P
Ar O
+
CO 2R
CO 2R
Ar= 2,4,6-trialkylphenyl
R= Me, Et
MW
Ar
P
CO 2R
O CO 2R

P-30
SYNTHESIS AND PROPERTIES OF PENTACOORDINATE PHOSPHORUS
COMPOUNDS CONTAINING A PENTACOODINATE SILICON ATOM
Hideaki Miyake, Naokazu Kano, and Takayuki Kawashima
Department of Chemistry, Graduate School of Science, The University of Tokyo
7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
Pentacoordinate phosphorus compounds have been vigorously studied because of their interesting
structures and reactivities. A silicon atom can also be a pentacoordinate state and pentacoordinate
silicon compounds have structures and reactivities similar to those of phosphorus analogues.
Although compounds bearing both pentacoordinate phosphorus and silicon atoms are attractive due
to their having two reactive sites, to the best of our knowledge, such a compound has never been
reported. We previously reported synthesis of various phosphoranes and silicates by taking
advantage of the Martin ligand which was known to stabilize effectively the pentacoordination
states. Here we report syntheses and properties of several compounds bearing both pentacoordinate
phosphorus and silicon atoms which are stabilized by the Martin ligands.
Reaction of phosphoranide 1 and silane 2, both of which bore two Martin ligands, in THF gave
compound 3a bearing both pentacoordinate phosphorus and silicon atoms bridged by the
ring-opened THF unit. The structure was identified by the NMR and mass spectra. Compound 3a is
the first example of a phosphorane bearing a pentacoordinate silicon atom.
Analogous compounds 3b–d, which had shorter methylene chains than 3a, were synthesized by
another method. Their detailed synthetic procedures, multinuclear NMR spectra of 3a-d and some
of their reactions will also be discussed.
57

P-31
SYNTHESIS OF A NOVEL APICAL–EQUATORIAL–EQUATORIAL TYPE
TRIDENTATE LIGAND AND CONSTRUCTION OF PENTACOORDINATE
PHOSPHORUS COMPOUNDS
Hideaki Yamamichi†, Shiro Matsukawa§, Yohsuke Yamamoto*,†
† Department of Chemistry, Graduate School of Science, Hiroshima University
1-3-1, Kagamiyama, Higashi-hiroshima 739-8526, Japan
§ Institute for Advanced Materials Research, Hiroshima University
1-3-1 Kagamiyama, Higashi-hiroshima 739-8530, Japan
A new tridentate ligand precursor 1,1-bis(2-iodophenyl)-2,2,2-trifluoroethanol (1), which can
bind an apical position and two equatorial positions of pentacoordinate trigonal bipyramidal (TBP)
structure rigidly, was prepared. Phosphine sulfides cis- and trans-3a were isolated from O-protected
bidentate ligand 2 in 29 and 31%, respectively. On the other hand, trans-3b was prepared as a single
stereoisomer. Phosphoranes bearing the tridentate ligand and a fluorine atom 4a and 4b were
prepared from 3a and 3b, respectively. It is interesting that both cis- and trans-3a gave the same
product 4a.
The structure of 4b was confirmed by the X-ray analysis. The more electronegative fluorine atom
was located at the apical position in the TBP structure (P–F length: 1.6513(10) Å).
The upfield-shifted 31P NMR signals and large coupling constants of 4a (
–46.2 ppm (d, 1JF–P
= 743 Hz)) and 4b (
–38.6 ppm (d, 1JF–P = 747 Hz)) in CDCl3 suggested that these compounds
have a pentacoordinate structure with a covalent P–F bond even in solution. A phosphorane bearing
an apical SMe group was also prepared.
58

P-34
THE CATALYTIC RING-CLOSURE REACTION IN THE PRESENCE OF
PHOSPHOROUS OXYCHLORIDE
Hui Wang,Renzhong Qiao
College of life science and technology, Beijing University of Chemical Technology, 100029 P. R. China
On the basis of many literatures and patents [1] , ramifications of s-triazolo[3,4-b]
-1,3,4-thiadiazoles have displayed many biological and physiological activities, including
antiphlogistic, analgesic, antibacterial, antifungal, anti-tumor, antianxity, insecticidal, herbicidal,
and plant-growth regulating activities. Consequently, such kinds of compounds are extensively
studies in recent years. 3-aryl-4-amino-5-thione-1,2,4-Triazoles [2] (1) and 6- substituted-4-
hydroxylnicotinic acids(2) were prepared as results of multistep reactions, the ring-closure of the
two compounds above in the presence of phosphorus oxychloride gave a series of compounds,
namely 3-aryl-6-(6-substituted-4chloropyridine-3-yl)-s-triazolo[3,4-b] -1,3,4-thia- diazoles(3),
whose structures have been established by MS, IR, 1 H NMR spectra. The reaction was carried out
for 6 to 8 hours when being refluxed with phosphorus oxychloride. During the process, the presence
of phosphorus oxychloride is necessary since it can activate the carbonyl of -COOH in 2a-2b,
enhance its electrophilic ability and improve the pericyclic reaction [3] , and also serve as appropriate
solvent. The process is displayed as below:
R1
N N
OH
R1
N
NH2 SH
+ R2
N
COOH
POCl3
relfux
N
N
N
S
N
1 2 3
R1: a. H; b. 2,4-OCH3 R2: a. H ; b. 6- CH3
Synthesis of 3-aryl-6-(6-substituted-4chloropyridine-3-yl)-s-triazolo[3,4-b]-1,3,4-thiadiazole
Keywords: 1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole; phosphorus oxychloride; Synthesis
REFERENCES
[1] ZHANG Zi-Yi, SUN Xiao-Wen. Heterocycles [J], 1998, 48: 561_584
[2] Reid J. R. , Heindel N. D. . J. HeterocyclicChem. [J], 1976, 13: 925_926
[3] Pant M. K. , Durgapal R. , Joshi P. C. . Indian J. Chem. [J], 1983, 22B: 712_713
59
Cl
N
R2

P-35
DITHIOPHOSPHORYLATION OF CYCLIC MONOTERPENES
Il’yas S. Nizamov 1, 2, Artiem V. Sofronov1, Rafael A. Cherkasov1, Liliya E. Nikitina3
1 Kazan State University, Kremlievskaya Str., 18, Kazan, 420008, Russia,
Email: Ilyas.Nizamov@ksu.ru Ilyas.Nizamov@ksu.ru
2 A.E. Arbuzov Institute of Organic and Physical Chemistry, Arbuzov Str., 8, Kazan, 420088, Russia,
3 Kazan State Medical University, Butlerov Str., 49, Kazan, 420012, Russia
There is a considerable interest in derivatives of cyclic monoterpene series compounds containing
functional groups due to their possible use as biological activity substances. The importance of
these compounds is also related to their skeleton structure transformations. O,O-Dialkyl
dithiophosphoric acids have been reported to react with terpenes such as -pinene and dipentene at
100-200 o C with the formation of additives for lubricants [1, 2]. We assumed that the initial
products obtained in these patent works undergo decompositions under severe conditions used. We
have carried out the reactions of dithiophosphoric acids with such terpenes as racemic camphene,
(+)-limonene, (1S)-(-)- -pinene and 3-carene under milder conditions and search appropriate
catalysts of addition reactions. We have found that these reactions occur at room temperature for
1-3 h in the presence of catalytic amounts of anhydrous ZnCl2 to yield adducts formed in
accordance with Markovnikow’s rule. In the case of camphene the adduct formation is accompanied
by skeleton transformation into norbornane structure.
S
(RO)
2
PSH +
ZnCl 2
(1 %)
20 o C, 1-2 h
S-P(OR)
2
R = Et, Pr-i
The reactions O,O-dialkyl dithiophosphoric acids with (+)-limonene proceed with the participation
of the exocyclic C=C bond.
S
(RO)
2
PSH +
ZnCl 2
(1 %)
20 o C, 2-3 h
60
S
S
S-P(OR) 2
R = Et, Pr-i
The reactions studied are facilitated by Lewis acid cataysts (NiCl2, CuCl, CuCl2, FeCl3,
BF3.Et2O, AlCl3). The reactions of O,O-dialkyl dithiophosphoric acids with (1S)-(-)- -pinene can
also be performed non-catalytically.
References
[1] Pat. US 2611728 (1952). / Barlett J.H., Rudel H.W., Cyphers E.B., Chem. Abstr. 1953, 43, 2930a.
[2] Pat. US 2665295 (1954). / Augustine F.B., Chem. Abstr. 1954, 48, 12807f.

P-36
BACKGROUNDS FOR THE TECHNOLOGY FOR THE PREPARATION OF
ORGANOPHOSPHOROUS PRECURSORS
Magdeev I.M., Budnikova Yu.H., Muslinkin A.A., Nabiullin V.N., Berdnik I.V.
A.E. Arbuzov Institute of Organic and Physical Chemistry, Russian Academy of Sciences, Arbuzov str. 8, Kazan,
Russia, 420088. E-mail: magdeev@iopc.knc.ru
Simple and effective techniques for the synthesis of methylolphosphonous,
bis(methylol)phosphinic and chloromethylphosphonic acids, their chlorine anhydrids, phosphonates
and phoshinates, possessing great synthetic potential, are elaborated.
New directions of electrochemical synthesis of tertiary phosphines and phosphates from the
elemental white phosphorus are suggested. The existing industrial technology of synthesis of
phosphorus compounds is based on the use of chlorine and chloride of phosphorus, thus causing
serious environmental problems and defining basic expenses of manufacture. Electrochemical
single-stage method was developed for preparation of phosphorus compounds, such as tertiary and
primary phosphines, trialkyl phosphates, including trioctylphosphate, phosphorous and
hypophosphorous acid etc. These products find applications as softeners, additives to lubricant oils
and liquid fuel, additives to polymers providing fire-resistance, and also as extracting agents,
complexing agents as well as precursors for synthesis of other substances for practical purposes.
61

P-37
SYNTHESIS OF 1,2-AZAPHOSPHETIDINES WITH AMINO ACID FRAGMENT
Inga M.Aladzheva, Olga V.Bykhovskaya, Pavel V.Petrovskii, Tatyana A.Mastryukova
A.N.Nesmeyanov Institute of Organoelement Compounds Russian Academy of Sciences, Vavilov str., 28, Moscow
119991, GSP-1, Russia, E-mail:shipov@ineos.ac.ru
Very few 1,2-azaphosphetidines are known in spite of the great interest to their 2-oxo derivatives
which are close structural analogues of azetidinones (β-lactams). Here we report a short synthetic
route to 2-oxo 1,2-azaphosphetidines with amino acid fragment 3 via intramolecular alkylation of
N-2-haloethyl amidophosphites 1. Two diastereomeres of compound 3 (R=Me) were obtained. By
intramolecular alkylation of aminophosphines 2, hitherto almost unknown 1,2-azaphosphetidinium
salts 4 were synthesized.
R 2PN
CH 2CH 2Cl
CHR 1 COOMe
1, 2
R=EtO (1), Ph (2)
R 1 =H, Me
Δ
R=EtO
-EtCl
R=Ph
EtO
O
P
Ph 2P
CHR 1 COOMe
N
3
CHR 1 COOMe
N
4
Cl
62
1. 6N HCl, Δ
2.
O
1. 6N HCl, Δ
2. O
O
O
P
OH
CH 2CH 2NH 2CHR 1 COOH
5
CH 2CH 2NH 2CHR 1 COO
2-Oxo-1,2-azaphosphetidines 3 readily hydrolyzed with the P-N bond cleavage; as a result of the
total hydrolysis, the derivatives both of β-aminophosphonic and α-amino carbon acids 5 with
potential biological activity were produced. The total hydrolysis of 1.2-azaphosphetidinium salts 4
resulted in the N-(2-diphenylphosphoryl)ethyl amino acids 6, potential complexing agents for
metals of biological interest (Cu, Co, Ni etc).
The work was supported by Russian Foundation for Basic Research (grant No. 05-03-3309).
Ph 2P
O
6

P-38
ASYMMETRIC SYNTHESES OF NEW PHOSPHONOTAXOIDS
Irina V. Guliaiko, Oleg I. Kolodiazhnyi
Institute of Bioorganic Chemistry and Petrochemistry, National Academy of Sciences of Ukraine
Murmanskaia 1, Kyiv, UKRAINE e-mail: oikol123@rambler.ru
The multiple asymmetric induction (multistereoselectivity) is an efficient method for increasing
the stereoselectivity of the phospho-aldol reaction by employing more than one chiral auxiliary. For
example chiral dialkylphosphites react with chiral aldehydes under the control by two chiral
auxiliaries, which reinforced one another, to yield the diastereomers 2 with very good de. Chiral
aldehydes 1 reacted with the (1R,2S,5R)-dimenthylphosphite or di-endo-bornylphosphite with the
formation of either chiral (1S,2S)- or (1R,2S)-1-hydroxy-2-aminophosphonic acids 4. The reaction
of dibenzylphenylalanynal 1 with tris(trimethylsilyl)phosphite afforded the
(1R,2S)--hydroxy- aminoalkylphosphonic acid 5, which was purified by recrystallisation. The
stereoselectivity of the reaction depended on the solvent, the nature of the bases and temperature.
The absolute configuration of the addition product was proved by NMR spectroscopy and X-ray
analysis
Ph
(R*O) 2 POH
OH
NBn 2
2
H 3 O +
Ph
DBU
P(O)(OR*) 2
OH
NBn 2
(1S,2S)-4
Ph
P(O)(OH) 2
NBn 2
1
63
O
P(OSiMe) 3
OH
(Me SiO) P(O)
3 2 Ph
NBn2 1) Crystallization
2) H3O +
3
OH
(HO) 2P(O) Ph
NBn 2
(1R,2S)-5
R*= (1R,2S,5R)-Mnt (80% ee), Brn (80% ee)
The chiral 1-hydroxy-2-aminophosphonic acids were used for modification of Baccatin III in the
synthesis of new taxoids – potential anticancer agents
Baccatine-III
AcCl/Py
BnNH
HO
Bn
DPC, DMAP
PO 3 H 2
BnNH
References
1. O. I. Kolodiazhnyi Tetrahedron: Asymmetry 2005, 16, 3295-3340
2. O. I. Kolodiazhnyi, I. V. Guliaiko J. Rus.Gen.Chem 2005, 75, 1933-1934
3. O. I. Kolodiazhnyi, I. V. Guliaiko J. Rus.Gen.Chem, in press
HO
Bn
OH
P
O
O
AcO
HO
OBz
O
AcO
OH
H
O

P-42
X-RAY CRYSTAL STRUCTURE OF HYDROLYSATES OF
TRIPHENYLPHOSPHINE DICHLORIDE
Jian Chen Zhang 1 , Wen Ping Shi 1 , Jun Xu 2 , Yu Fen Zhao 3
1
Department of Chemical Defense, Institute of Chemical Defense, Beijing 102205
2
Department of Humanities and Basic Sciences, Zhengzhou College of Animal Husbandry Engineering
Zhengzhou 450011
3
The Key Laboratory for Chemical Biology of Fujian Province, Department of Chemistry, University, Xiamen 361005
The Appel coupling reagents triphenylphosphine and hexachloroethane were used in peptide
synthesis 1,2 . The reaction of triphenylphosphine with hexachloroethane would produce
triphenylphosphine dichloride (Ph3PCl2). Until recently, Godfrey and coworkers 3 prepared the
solid state Ph3PCl2, which was characterized by X-ray crystal diffraction. In the course of
studying the reaction character of triphenylphosphine and hexachloroethane, two hydrolysates of
triphenylphosphine dichloride, [Ph3POH]Cl and [Ph3PO]2[H2O][H3O]Cl, were obtained.
Triphenylphosphine dichloride was prepared from the direct reaction of triphenylphosphine with
hexachloroethane in benzene in a 1:1 stoichiometric ratio at room temperature, and the reaction
procedure was traced by 31 PNMR spectra. It was found that the peak of triphenylphosphine (δ
-4.76 ppm) was gradually decreased; meanwhile the peak at δ -44 ppm was appeared and gradually
increased. Compared with the NMR spectrum of crystalline Ph3PCl2 in C6D6 (δ –47 ppm) 3-6 , this
value of δ –44 ppm was confirmed the resonance of the non-solvated molecular species Ph3PCl2.
In addition, the peak of δ 27 ppm was unchangeable in the reaction procedure, which was validated
with the authentic sample of triphenylphosphine oxide.
Under an atmosphere of dry nitrogen, no solid could isolate from the above solution. But under
an atmosphere of air, a small quantity of colorless crystals was observed. Analyzed by 31 PNMR and
ESI-MS spectra, it was validated to be not the molecular structure Ph3PCl2 but the hydrolysates of
Ph3PCl2. Therefore, this was considered that the reaction solution possibly adsorbed moisture
from air and triphenylphosphine dichloride was hydrolyzed. Therefore, added 1 or 2
stoichiometric ratio water to the reaction solution respectively, two colorless crystals were gradually
produced on standing at room temperature for ca. 4 hrs. Those were chosen for analysis by single
crystal X-ray diffraction and were validated as [Ph3POH]Cl (Figure 1) and [Ph3PO]2[H2O][H3O]Cl
(Figure 2), respectively. They are ionic species and tetrahedral structure. Two crystals were
dissolved in deuterated chloroform and a single resonance was observed in the NMR spectrum at δ
40, 35 ppm, respectively.
Figure 1 X-ray crystal structure of [Ph3POH]Cl. Figure 2 X-ray crystal structure of [Ph3PO]2[H2O][H3O]Cl.
64

References
1. R. Appel and H. Scholer, Chem. Ber., 1979,112, 1065.
2. R. Appel and L. Willms, Chem. Ber., 1979, 112, 1057.
3. S. M. Godfrey, C. A. Mcauliffe, R. G. Pritchard, J. M. Sheffield, Chem. Commun., 1998, 921.
4. M. A. H. A. Al-Juboori, P. N. Gates, A. S. Muir, J. Chem. Soc., Chem. Commun., 1991, 1270.
5. S. M. Godfrey, C. A. Mcauliffe, R. G. Pritchard, J. M. Sheffield, Chem. Commun., 1996, 2521.
6. G. Tang, G. J. Ahou, F. Ni, L. M. Hu, Y. F. Zhao, Chin. Chem. Lett., 2005, 16(3), 385.
65

P-46
THE SYNTHESIS OF 7,11,18,21-TETRAOXA-1,3,5,13,15,17-HEXAAZA-2,4,6λ5,12λ5,
14,16-HEXAPHOSPHATRISPIRO[5.2.2.5.2.2]HENEICOSA-1,3,5,12,14,16-HEXAENE
Ju Zhiyu 1 , Zou Ruyi 1 , Yin Zhengming 1 , Ye Yong 1* , Liao Xincheng 1 , Zhao Yufen 1,2*
1
Key Laboratory of Chemical Biology and Organic Chemistry of Henan Province, Department of Chemistry,
Zhengzhou University , Zhengzhou 450052, PR China
2
Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology, Ministry of Education, Department of
Chemistry, Tsinghua University , Beijing 100084, PR China
In 1970’s, cyclophosphazene derivatives, kinds of widely researched compounds, can be applied
as flame retardant of self-extinguish ability in plastics and fibers. 1 Many of articles has also reported
that they can form an intumescent flame retardant system with their excellent fire retardant
properties. 2-3 It was reported that the reaction of hexachloro- cyclophosphazene (HCCP) with
pentaerythritol(2:1) gave rise to three kinds of spirane derivatives (Scheme 1). 4 According to
reference, the compound 1 can be obtained in 15% yield. Recently, we successfully synthesized
compound 1 in a moderate yield. The title compound was obtained in 48% yield by adding solid
pentaerythritol to the solution of HCCP below -5 0 C. After stirred for 10 h, then the solution was
refluxed for approximately 24 h, Further researches are now in progress in our laboratory.
Cl
Cl P
N
N Cl HO
P +
Cl P N
Cl
Cl HO
OH CH2Cl2 OH
Py
Cl
Cl P N O
N P
Cl P N O
Cl
1
Cl
Cl
O N P Cl Cl P N O
P N + N P
O N P Cl Cl P N O
Cl
Cl 2
Scheme 1
66
Cl
Cl
O P N Cl Cl P N O
N P + N P
O P N Cl Cl P N O
Cl
Cl
Project supported by the Chinese National Natural Science Foundation (NO.20602032).
References
1. Kumar D, Fohlen G M, Parker J A., J. Polym. Sci., 1984, 22, 927-943.
2. Hofle G, Steglich W.D., Angew. Chem. Int. Ed. Engl., 1978, 17, 569.
3. Liang HB, Asif A, Shi WF., Polym. Degrad. Stab., 2005, 87, 495.
4. Al-Madfa H.A., Shaw L.S., Shaw R.A., Phosphorus, Sulfur, Silicon, 1991, 56, 133-142.
3
OH
OH

P-47
P-NITROPHENOXYCARBONYLPHOSPHONATE DIESTERS-POTENT REAGENTS
FOR THE SYNTHESIS OF HINDERED CARBAMOYLPHOSPHONATES
Julia Frant, Irena Beylis, Naama Mussai, Reuven Reich and Eli Breuer
Department of Medicinal Chemistry, School of Pharmacy,
The Hebrew University of Jerusalem, Jerusalem, 91120 Israel
Matrix metalloproteinases (MMPs) are a family of about 26 zinc-dependent endopeptidases,
which collectively have the capacity to degrade all the major components of the extracellular matrix.
Although the MMPs play a crucial role in physiological tissue remodeling, growth and repair, their
over-expression has been linked with severe chronic pathological conditions, including cancer,
arthritis, several cardiovascular disorders and others. The efficient inhibition of MMPs is, therefore,
an important scientific and therapeutic target, which has attracted considerable attention within
academia and industry for the last two decades. Yet, in spite of intensive worldwide research, which
has yielded a multitude of highly in vitro potent inhibitors, no clinically useful inhibitor has been
achieved.
We are involved in a research program directed toward the design and synthesis of new MMP
inhibitors, based on the carbamoylphosphonic functional group. , In this context, we have envisioned
several sterically hindered carbamoylphosphonates. However, these target compounds were not
accessible by the existing synthetic methods, namely by the reaction of a hindered cycloalkylamine
with trialkyl phosphonothiolformate, or by conversion of the amine to an isocyanate, followed by
reaction with a dialkyl H-phosphonate.
We have considered that the reactivity of the carbonyl group in trialkyl phosphono-thiolformate,
[RS-CO-P(O)(OR)2], could be increased by replacing the alkylmercapto group with the more
strongly electron withdrawing p-nitrophenyl group. The resulting p-nitrophenyl dialkyl
phosphonoformate [O2N-C6H4-CO-P(O)(OR)2], indeed proved to be a far more reactive than
trialkyl phosphonothiolformate, and hindered carbamoylphosphonates, that could not be obtained
even under harsh conditions such as prolonged heating and the presence of catalysts, this reagent
gave the desired products in a few minutes at room temperature.
Our poster will present examples of compounds that were successfully synthesized by reacting
various sterically hindered amines with p-nitrophenyl dialkyl phosphonoformates.
67

P-48
PHOSPHORYLATION OF DIHYDROXY ANTHRAQUINONES BY
ATHERTON-TODD REACTION
Jun-Feng Zhao, 1 Xian-Li Wu 1 , Si-Xing Zhang, 1 Xin-Cheng Liao,* 1 Shu-Xia Cao 1 , Yan-Chun Guo 1 1, 2
, and Yu-Fen Zhao
1. Department of Chemistry, the Key Laboratory of Chemical Biology, Zhengzhou University, Zhengzhou 450052,
Henan,P.R.China E-mail: lxc66@zzu.edu.cn Tel: +86371-67767050
2. Department of Chemistry, the Key Laboratory for Bioorganic Phosphorus Chemistry and Chemical Biology, Ministry
of Education, School of Life Sciences and Engineering, Tsinghua University, Beijing 100084, P.R.China
The phosphorylation and dephosphorylation of proteins play an important role in regulation
complicated biochemical processes. Moreover,phosphorylated biomolecules and medical molecules
have many unique activities and characteristics. We studied the phosphorylation of dihydroxy
anthraquinones by Atherton-Todd reaction. Two kinds of dihydroxy anthraquinones was
successfully phosphorylated by diethylphophite (DEPPH) and diisopropylphophite(DIPPH).
R 2
O
O
OH
R 1
+
O
P
H
RO OR
68
HCCl 3/NEt 3
R=CH 2CH 3 or CH(CH 3) 2
1a-b 2a-d
Scheme 1. Phosphorylation of different dihydroxy anthraquinones
R 2'
Table 1. Particular substituents of all compounds
Compound No. R1 (R1’) R2 (R2’)
1a OH H
1b H OH
2a OP(O)(OCH2CH3)2 H
2b OP(O)(OCH(CH3)2)2 H
2c H OP(O)(OCH2CH3)2
2d H OP(O)(OCH(CH3)2)2
O
O
OH
R 1'

P-49
DECOMPOSITION REACTION OF
TETRA-HYDROXYMETHYLPHOSPHONIUM CHLORIDE
Kaiqi Shi, Ya Li, Lan Jiang, Qiaoyun Ye, Shuangxi Shao,
Institute of Applied Chemistry, NingboUniversity of Technology, Ningbo, China 315016
At present, tetra-hydroxymethyl phosphonium chloride (THPC) is widely used in flame retardant
finish, industrial circulating cooling water treatment and leather manufacture industry, and it will
decompose and may yield tri-hydroxymethyl phosphonium (THP), tri-hydroxymethyl phosphonium
hydroxide (THPH), or tri-hydroxymethyl phosphine oxide (THPO) in application process. To
understand the decomposition reaction of THPC in different pH condition, the experiment is carried
out. Firstly, we determine the THPC content of THPC solution with pH=4.0~13.0 by the indirect
iodimetry method, respectively. When pH=4.0~6.0, the THPC content is between
70.34%~71.33%. When pH=7.0~9.0, the THPC content is between 56.90%~58.12%, and when
pH=10.0~13.0, the THPC content is between 0.22%~0.94%. Consequently, we find that THPC
content decreases when pH of the THPC solution rising, and there are two sudden changes at
pH=6.0 and pH=9.0. Then, by FT-IR and 31 P NMR, we analyze the structures of phosphorus
compounds in the THPC solution at pH=4.0, pH=6.0 and pH=9.0. The 31 P NMR results show that
the chemical shifts of -27ppm, -23ppm, 26ppm and 49ppm are the absorptions of THPH, THP,
THPC and THPO respectively. The contents of THP, THPH and THPO increase while the content
of THPC decreases. At pH=6.0, the absorption of THPH appears. When pH=9.0, the absorption
of THPC vanishes. Therefore, the decomposition reaction of THPC may reach an equilibrium
between pH=6.0 and pH=9.0, and the complete decomposition would take place when pH>9.0.
Furthermore, the Wang-Ford charge distributions of the main phosphorus compounds in THPC
solution are also calculated by the Cambridge chemical software to investigate their reactivity.
From the charge distributions analysis, we conclude that THP is the most stable phosphorus
compound, while THPO, comparing with the other three phosphorus compounds, have higher
reactivity due to its high asymmetric charge distribution, which could give a favorable guide in
application.
69

P-50
PHOSPHONILATION OF 1,3-DIARYL-2,3-DIHYDRO-1Н-NAPHTH[1,2-Е][1,3]OXAZINE
BY DIALKYL AND DIARYL PHOSPHONATES
Kirill E. Metlushka 1 , Vladimir A. Alfonsov 1 , Charles E. McKenna 2 , Boris A. Kashemirov 2 , Olga N. Kataeva 1 , Viktor F.
Zheltukhin 1 , Dilyara N. Sadkova 1 , Alexey B. Dobrynin 1
1A.E.Arbuzov Institute of Organic and Physical Chemistry, Kazan Scientific Center of the Russian Academy of
Sciences, 8 Arbuzov St., Kazan, 420088 Russian Federation. Email: alfonsov@iopc.knc.ru
2Department of Chemistry, University of Southern California, Los Angeles, CA 90089 USA
Chiral 1-(α-aminobenzyl)-2-naphthols, known as Betti bases, are available from the condensation
of β-naphtol with benzaldehydes and ammonia or amines. These compounds are of interest to
chemists who work on asymmetric syntheses and are seeking enantiopure chiral inductors or chiral
precursors. Recently, Hu et al. (J. Org. Chem., 2005, 70, 8617) reported resolution of isolated Betti
base as an L-(+)-tartaric acid salt. We report here resolution of the Betti base condensation product
1 (formed in situ from 2-naphthol, ammonia and benzaldehyde) using L-(+)-tartaric acid. The
oxazine 1 in CDCl3 solution exists as a mixture of tautomers of oxazine and imine forms,
resonances from all forms being present in the 1H NMR spectrum.
The products of this reaction are (S)-(+)-1-(α-aminobenzyl)-2- naphthol tartrate 2, the acetal of
benzaldehyde and tartaric acid 3 and (R)-(-)-1,3-diaryl-2,3-dihydro-1Н-naphth[1,2-е][1,3]oxazine,
which can be easily separated by crystallization. The addition reactions of dialkyl- and
diphenylphosphite with racemic and enantiopure 1 and its 4-arylsubstituted derivatives have also
been studied. The reactions proceed diastereoselectively with formation of aminophosphonates 4.
This work was supported by the Civilian Research and Development Foundation (grant no.
RUC2-2638-KA-05) and the Russian Foundation for Basic Research (grant no. 03-03-33082).
70

P-51
DIMENTHYL (2R)-2-HYDROXY-3-CHLOROPROPYLPHOSPHONATE – ACCESSIBLE
CHIRON FOR THE ASYMMETRIC SYNTHESIS OF HYDROXYPHOSPHONATES
Kolodiazhnyi O.I., Nesterov V.V.
Institute of Bioorganic Chemistry and Petrochemistry, National Academy of Sciences of Ukraine,
Murmanskaia 1, Kyiv, UKRAINE e-mail: oikol123@rambler.ru
Optically pure dimenthyl (2R)-2-hydroxy-3-chloropropylphosphonate 1 was synthesized by
reaction of the di(1R,2S,5R)-menthylketophosphonate 2 with the chiral complex 3 [1]. The
reduction of the ketophosphonate 2 by this complex proceeded under the control of double
asymmetric induction [2] and resulted in the formation of the hydroxyphosphonate 1 with high
optical and chemical yields. The compound 1 was isolated as a crystalline stereochemically pure
substance with ~100 % de. The compound 1 is accessible chiron, which was used for the
preparation of a number of biologically important enantiomerically pure products, including
amino- -hydroxybutyric acid (phospho-GABOB) 4, 2,3-aziridinopropylphosphonate 6,
2,3-epoxypropylphosphonate 7, phospho-carnitine 8, etc in multigramme scale. The structure,
chemical and optical purity, absolute configurations of all synthesized compounds were carefully
investigated [3,4].
(RO) 2 P
O
O
(RO) 2 P(O)
R=Mnt, H;
2
O
HO OH
H
O -
B
O
8
H
3
OH
H
O
Cl
Na +
+
NMe3 Me 3 N
(RO) 2 P(O)
O
(RO) 2 P
O
(RO) 2 P
71
OH
H
4
OH
H
1, ~100% de
O
H
NH 2
Cl
NaN 3
(RO) 2 P(O)
(RO) 2 P(O)
References
1 V. V. Nesterov and O. I. Kolodiazhnyi Tetrahedron: Asymmetry 2006, 17, 1023-1025
2 O.I. Kolodiazhnyi Tetrahedron, 2003, 59, 5953-6018.
3 V. V. Nesterov and O. I. Kolodiazhnyi J. Rus. Gen. Chem. 2006, 76, 1068-1077
4 O. I. Kolodiazhnyi Tetrahedron: Asymmetry 2005, 16, 3295-3340
3
7
OH
H
(R)-5
(R)- 6
N 3
H
N
H

P-55
SYNTHESIS N-PHOSPHORYLATED CHRYSIN-7-YL AMINO ACID ESTERS
Li Wenfeng 1 , Chen Xiaolan 1 , Yuan Jinwei 1 , Qu Lingbo 1,2 , Zhao Yufen 1,3
1
Department of Chemistry, Zhengzhou University, Zhengzhou, 450052, P. R. China
2
Anyang Normal College, Henan Province, Anyang, 455002, P. R. China
1, 3
The Key Laboratory for Bioorganic Phosphorus Chemistry, Department of Chemistry School Life Sciences and
Engineering, Tsinghua University, Beijing, 10084, P. R. China
Chrysin, 5,7-dihydroxyflavone, which is widely distributed in plants, is known to have many
biological activities including antibacterial, antioxidant, anti-inflammatory, anti-allergic, anticancer,
anti-estrogenic, and anoxiolytic activities. [1] Efforts to improve the biological activity of chrysin
have led to the synthesis of derivatives by appropriate modification. [2] The modification mainly
centers on aromatic ring (either A or C) substitutions in chrysin. N-phosphorylated amino acids
have been shown to play an important role in probing the origin of life. At the same time, they have
wide applications in the fields of biotechnology, and medicine. [3] Within the pharmaceutical
industry, phosphate esters are often used as pro-drugs to increase the bio-availability of the a drug. [4]
In the work described in this paper, we introduce an N-phosphorylated amino acid into chrysin
modification. Five new analogs have been synthesized(scheme1) and their structures have been
determined by ESI-MS, NMR and IR.
HOOC
R
NH 2
HO
O
O
((CH 3) 2CHO) 2-PH
H 2 O/Et3N/EtOH OH O
THF, DMAP, DCC
72
R
O
HOOC
O
NH
P O
O
R
O
NH
O
P O
O
O
OH O
a~e
a: R=Methyl
b: R=isopropyl
c: R=isobutyl
d: R=2-butyl
e:phosphated L-Proline
Scheme 1
References
1. Hecker, M.; Preiss, C.; Klemm, P.; Busse, R. Br. J. Pharmacol. 1996, 118, 2178.
Fishkin, R. J.; Winslow, J. T. Psychopharmacology (Berl.) 1997, 132, 335
2. Shin, J. S.; Kim, K. S.; Kim, M. B. et al. Bioorg. Med. Chem. Lett. 1999, 9, 869;
Dao, T.-T.; Chi, Y.-S.; Kim,J.; Bioorg. Med. Chem. Lett. 2004, 14, 1165.
3. Zhao Yufen; Zhang Jianchen; Xu Jun et al Chinese Jounal of Organic Chemistry, 2004,24,6609
4. Jones S.; Selitsianos D.; Thompson K. J. et al. J. Org. Chem. 2003, 68(13), 5211-5216.

P-57
APPLICATIONS OF LAWASSON’S REAGENT IN SYNTHESIS OF BIOLOGICALLY
ACTIVE PHOPSHORUS-HETEROCYCLES
Liang-Nian He*, Jin-Quan Wang, Ya Du, Fei Cai
State Key Lab of Elemento-organic Chemistry, Nankai University, Tianjin, 300071, P. R. China
Our research interest has been focused on the development of new synthetic methodology
centered around biologically active phosphorus heterocycles, because functionalized phosphorus
heterocycles and their derivatives are of great interest bioactive substances with various properties.
We disclosed a methodology for 5-membered and 6-membered phosphorus heterocycles with
biological activity via cyclization of Lawesson’s reagent, 2,4-bis(4-methoxyphenyl)-1,3,2,4-
dithiadiphosphetane-2,4-disufide, with bifunctional substrates. This cyclization reaction of
Lawesson’s reagent was successfully applicable to other bifunctional compounds to afford different
kinds of phosphorus-heterocycles. That prompts us to develop a method for synthesis of the fused,
spiro phosphorus-heterocycles, 7-membered P-heterocycles, 6-membered P, S-heterocycles and
other P- and S-containing compounds, as shown in Scheme 1. Preliminary bioassays revealed that
some of the title compounds possess selective herbicidal activity.
Ar
S
R 2
R 1
R 2
O
P
O
Cl
Cl
Cl
O P
O P
Cl
S
S
Ar
Ar
S
N
O S
P
Ar
O
P
N
NEt 2
O
R
N
R 2
R 1
R 2
S
N
N
P
Cl
Cl
73
Ar
O
N
R 1 R 2 R 1
S
Cl
O
O P
S
Ar
Cl
N
S
P
N
NEt 2
S
S
N
N
N
N
P O
Ar
S
P O
Ar
Scheme 1
References
1. M. Jesberger, T. P. Davis, L. Barner, Synthesis, 2003, (13), 1929.
2. a) L. He, Y. Luo, K. Li, G. Yang, M. Ding, X. Liu, T. Wu, Phosphorus, Sulfur, and Silicon and the Related
Elements, 2002, 177, 2675; b) L. He, Y. Luo, K. Li, M. Ding, A. Lu, X. Liu, T. Wu, F. Cai, Synth. Commun., 2002,
33(9), 1415; c) L. He, Y. Luo, M. Ding, A. Lu, X. Liu, T. Wu, F. Cai, Heteroatom Chem., 2001, 12(6), 497; d) Y. Luo,
L. He, M. Ding, G. Yang, A. Lu, X. Liu, T. Wu, Heterocyclic Commun., 2001, 7(1), 37; e) L. He, Y. Luo, M. Ding, A.
Lu, X. Liu, T. Wu, F. Cai, Heteroatom Chem., 2001, 12(6), 497; f) L.-N. He, R.-X., Zhuo, R.-Y. Chen, Y.-J. Zhang,
Heteroatom Chem., 1999, 10(2), 105; g) L.-N. He, T.-B. Huang, F. Cai, R.-Y. Chen, Phosphorus, Sulfur, and Silicon
and the Related Elements, 1998, 132, 147; h) L.-N. He, R.-X. Zhuo, R.-Y. Chen, J. Zhou, Synth. Commun., 1997, 27
(16), 2853.
R 2

P-62
PHOSPHOROUS ACID NUCLEOPHILIC ADDITION AT CARBONYL GROUPS
Li-Ping Zhang a,b , LingBo Qu a , Yu-Fen Zhao *a,c,d
a Key Laboratory of Chem-biology and Organic, Zhengzhou University, Henan Province, 450052, P. R. China;
b Department of Chemistry, Anyang Normal University, Anyang 455002, P. R. China;
c Key Laboratory of Bioorganic Phosphorus Chemistry of the Education Ministry, Department of Chemistry, School of
Life Sciences and Engineering, Tsinghua University, Beijing 100084, P. R. China;
d The Key Laboratory for Chemical Biology of Fujian Province, Department of Chemistry, College of Chemistry and
Chemical Engineering, Xiamen University, Xiamen 361005, P. R. China
In recent years a renewed interest in the synthesis of organophosphorus compounds has appeared.
This has been the result principally of the development of new applications of materials bearing a
carbon-phosphorus linkage for a variety of industrial uses. Initial investigations of the addition of
trivalent phosphorus to carbonyl compounds were performed with the use of either trialkyl or
dialkyl phosphites, yielding the corresponding phosphonate esters. Free acid was obtained by
hydrolysis with dil. HCl. This paper represents a particularly convenient method for generating
organophosphonic acid compounds. Series of α-hydroxylalkylphosphonic acid, unsaturated
phosphonic acid, conjugated phosphono carboxylic acid, substituted
1-hydroxyl-methane-1,1-diphosphonic acid were synthesized by reacting phosphorous acid (H3PO3)
directly with aldehydes, ketones, carbonyl ester and carbonyl chloride.
Reference
[1] Abramov, V. S.; Dmitrieva, R. V.; Kapustina, A. S. Reaction of dialkyl phosphorous acids with aldehydes and
ketones. IV. Butyl and allyl esters of -hydroxyalkylphosphonic acids. Zhurnal Obshchei Khimii (1953), 23 257-62.
[2] Sekine, Mitsuo; Yamamoto, Isamu; Hashizume, Akio; Hata, Tsujiaki. Silyl phosphites.V. The reactions of
tris(trimethylsilyl) phosphite with carbonyl compounds. Chemistry Letters (1977), (5), 485-8.
[3] Pudovik, A. N. New method of synthesis of esters of phosphonocarboxylic acids and their derivatives. Doklady
Akademii Nauk SSSR (1952), 85 349-52.
[4] Blazis, Vincent J.; Koeller, Kevin J.; Spilling, Christopher D. Asymmetric synthesis of -hydroxy-phosphonamides,
phosphonates and phosphonic acids. Tetrahedron: Asymmetry (1994), 5(4), 499-502.
[5] Ginsburg, V. A.; Yakubovich, A. Ya. Reaction of aldehydes with trialkyl phosphites.
Zhurnal Obshchei Khimii (1960), 30 3979-87.
[6] Schuelke, Ulrich. Phosphonylation by tetraphosphorus hexoxide. Phosphorus, Sulfur and Silicon and the Related
Elements (1990), 51-52(1-4), 153-6.
74

P-64
THE SYNTHESIS OF TETRACYCLIC PHOSPHORATE
M.A.Pudovik, L.K.Kibardina, S.A.Terent’eva, O.N.Kataeva, G.A.Chmutova, V.A.Alfonsov
A.E.Arbuzov Institute of Organic and Physical Chemistry, Kazan Scientific Centre of the Russian Academy of Sciences,
Arbuzov Str., 8, 420088 Kazan, Russian Federation. Fax: +7 8432 75 5322; e-mail: pudovik@iopc.knc.ru
A reaction of ethylenechlorophosphite with diimine 1 was investigated. It proceeds in mild
conditions and results in the formation of tetracyclic phosphorate 5. Reaction pathways to this
product are proposed.
CH
NCH2CH2N CH
OH OH
1
CH
NCH2CH2N CH
O H
P
O
CH
O O
N
3
CH 2CH 2
NH
CH
O O
P
O O
+
O
O
PCl
75
CH
CH
NCH2CH2N CH
O
OH PO
O
2
NCH3CH2NH
CH
O O
P
O O
5
We suppose, the phosphorylation of the compound 1 takes place on the first stage of the reaction
with the formation of phosphite 2. The phosphite 2 then turns into P-H-spyrophosphorane 3, which
rearranges by intramolecular addition of the P–H bond to the C=N double bond to furnish the
tricyclic phosphorane 4. On the last stage the formation of intramolecular N→P bond takes place to
form final product – the phosphorate 5.
The stability of all participants of the reaction is evaluated by the means of the functional density
theory (Priroda/PBE/3z3 and B3LYP/6-31G (d, p) with complete optimization of the geometry; the
thermodynamic utility of 3→5 transformation is revealed. The calculated geometrical
characteristics of the structure 5 are in agreement with the X-Ray data.
This study was supported by the Russian Foundation for Basic Research (grant no. 06-03-32085).
4

P-65
ABNORMAL REACTIVITY OF ARYLAMINOMETHYLENEBISPHOSPHONATES.
AMINOMETHYLATION ON BENZENE RING IN BASE MEDIUM
M.O.Lozinsky, A.L.Chuiko
Institute of Organic Chemistry of the Nathional Аcademy of Sciences of Ukraine
Murmanskaya str. 5, Kyiv 02094, Ukraine Chuikoal@yahoo.com
We have found, that aminogroups of (arylamino)methylenebisphosphonic acids are unexpectedly
weak as bases.
R
O
PCl3 /H2O R
N
H
H
76
N
H
PO 3 H 2
R = p-Me-, p-H2N-, p-HO-, p-Cl-, m-O2N-.
PO 3 H 2
5 new acids were synthesised according to the recently published method [1]. Only one of them
(R = p-Me-) seems to form internal salt. This compound is well crystallisible from water. Other
synthesised (arylamino)methylenebisphosphonic acids don't form internal salts. They were isolaled
as salts with corresponding anilynes, and did not form free acids at treatment with HCl. Thus,
[(4-aminophenyl)amino]methylenebisphosphonic acid was isolated as a salt with 1/2 molecule of
p-phenylenediamine, and this salt does not lose significant amount of the phenylenediamine at
recrystallisation from 5% HCl:
H N
H N
2
2
PO3H2 • 2
NH N PO H
2
3 2
H
We suppose, that this weakness of the aminogroups is the result of conjugation with benzene ring,
which is stronger than is usual for anilynes. It is confirmed by high reactivity of the benzene ring at
electrofilic attack. Thus, we have realized aminomethylation of [(4-methylphenyl)amino]methylenebisphosphonic
acid in water in the presence of amine excess:
H C 3
N
H
PO H 3 2
PO H 3 2
O O
NH;
CH2 O
H C 3
N N
H
PO H 3 2
PO H 3 2
? O NH
We have not found in literature a reaction example of aminomethylation on benzene ring in basic media.
Reference
[1] Mingshu Wu, Ruyu Chen, You Huang. Synth. Comm. №8. 2004. p.1393-98.

P-69
THE PREPARATION OF NITROGEN-CONTAINING
HETEROARYOYLPHOSPHONATES
AND THEIR REACTIONS WITH TRIALKYL PHOSPHITES
D. Vaughan Griffiths, Michael C. Salt and Helen V. Taylor
School of Biological and Chemical Sciences, Queen Mary, University of London,
Mile End Road, London, E1 4NS, UK
As part of our wider studies of aroyl- and heteroaroyl-phosphonates we have been investigating
α-ketophosphonates based on the pyrrole and pyridine ring systems. These systems have proved to be
much more difficult to prepare than the furan- and thiophene-based systems we have also been
studying. Nevertheless, we have now successfully prepared pyrrol-2-ylcarbonylphosphonates such 1
(R=Me and Ph) and have investigated their reactions with trimethyl phosphite. This results in
deoxygenation of the carbonyl group to give the corresponding carbene intermediates 2 which are
then trapped by the trimethyl phosphite present in the reaction mixture to give the ylidic
phosphonates 3. We have so far seen no evidence of carbene insertion into the substituent R.
4
O
P(OMe) 2
77
O
O
N
O
P(OMe) 2
N
C
N
C
R
O
R
P(OMe) 2
N
C
1 2 R
P(OMe) 3
3
In contrast, the pyridin-3-ylcarbonylphosphonate system 4 (R=H) reacts with further phosphite
leading to the formation of 5. However, this mode of attack is suppressed if a substituent is placed at
the 2-position on the ring. For example, the reaction of the 2-phenoxy-substituted system 4 (R=OPh)
results in deoxygenation of the carbonyl group resulting in carbene formation and the formation of
the insertion product 6.
O
C
O
P(OMe) 2
MeO
O O
OMe
OMe
P
O O
O
(MeO) 2P
N R
(MeO) 2P
P(OMe) 2
3-Pyr 3-Pyr
N O
N
O
C
O
P(OMe) 2
N
O
C
5 6
P(OMe) 2
O P(O)(OMe) 2
C P(O)(OMe) 2
7
8 N 9
For the unsubstituted 2- and 4-pyridinylcarbonyl chlorides the reaction with trimethyl phosphite
proceeds beyond the initial formation of the -ketophosphonates 7 and 8 to give the corresponding
diphosphorus compounds 9. The impact of having substituents ortho to the ketophosphonate group in
these systems is currently being assessed.
O
C

P-71
REACTION OF RACEMIC AND NON-RACEMIC SILYLATED
(1-PHENYL)ETHYLAMINE WITH
O-PHENYLCHLOROMETHYLISOTHIOCYANATOTHIOPHOSPHONATE. SYNTHESIS
OF OPTICALLY ACTIVE 1,3,4-THIAZAPHOSPHOLE
Ludmila K. Kibardina, Mikhail A. Pudovik, ∗ Natalia A. Khailova, Vladimir A. Alfonsov, Olga N. Kataeva
A.E.Arbuzov Institute of Organic and Physical Chemistry, Kazan Scientific Centre of the Russian Academy of
Sciences, Arbuzov Str., 8, 420088 Kazan, Russian Federation. Fax: +7 8432 75 5322;
e-mail: pudovik@iopc.knc.ru
Optically active R-(+)-N-trimethylsilyl(1-phenyl)ethylamine 2a was synthesized by interaction of
R-(+)-(1-phenyl)ethylamine with trimethylchlorosilane in the presence of a base.
R-(+ )-PhCHNH 2
Me
+ Me 3SiCl
-Et3N . HCl
78
Et 3N
R-(+ )-PhCHNHSiMe 3
Me
2a
The reaction of isothiocyanate 1 with silylamine 2a proceeds easily in an ether at room
temperature and results in a mixture of 4a and 4b with chemical shifts δР 120.05 and 19.77 ppm. in
29 : 71 % ratio correspondingly. Diastereomer 4b crystallized from a reaction mixture after 24 h
and it’s angle of the specific rotation was [α]D 20 +240.5 (c=3.87).
S
PhO
PNCS +
ClCH 2
1
S
PhO
P
N
C
S
2a
4a RcRp
Me
R-(+)-PhCHNHSiMe 3
Me
NH C
Ph
H
+
S
PhO
P
N
S
S
PhO P N C NH C
Ph
ClCH2 SiMe 3 H
C
S
4b RcSp
3a RcRp
NH
S
+
P N C NH C
ClCH2
Ph
PhO SiMe 3 H
S
3b RcSp
Me
C
Ph
H
Me
Me
-Me 3SiCl
X-ray structure data reveal that the configuration of carbon and phosphorus atoms in these
compounds is the opposite. If the configuration of chiral carbon atom in isomer 4b is R and is
determined by the configuration of amine used, then the absolute configuration of the phosphorus
atom is S. That is the preferred covalent bonding with the enantiomer possessing the opposite
configuration of the chiral center takes place in the course of the reaction of chiral isothiocyanate 1
with amine 2a. It must be due to the influence of steric factors on the first stage of the reaction –
addition of silylamine to isothiocyanate with the formation of appropriate thiourea. We failed to fix
it spectral and that indicates the fast second stage - cyclization. And at this stage there is no changes
in the configuration of chiral centers and thus it does not render an influence on stereochemical
result of the process.
This study was supported by the Russian Foundation for Basic Research (grant no. 06-03-32085).

P-73
STUDY OF REACTION OF ACETYLENIC PHOSPHONATES
WITH CARBANIONIC NUCLEOPHILES
N.G. Didkovskii, A.I Petryanina, A.V. Dogadina, N.I. Svintsitskaya and B.I. Ionin
St. Petersburg State Technological Institute26 Moskovskii pr., St. Petersburg 190013, Russia.
E-mail: bi@thesa.ru
Reactions of chloroacetylenephosphonates and acetylenediphosphonates with carbanionic
nucleophiles formed in situ by interaction of a series of CH-acids with potassium carbonate are
studied. As the initial CH-acids are taken: malonic dinitrile and esters, cyanoacetic ester,
acetylacetone, dimedone, etc. Reactions performed are shown convenient for creation new C–C
bonds in organophosphorus compounds and are prospective for various syntheses.
O O
P Cl RCCH2CR' O
P =
P(OCH3) 2 ; R R ' = = CH3 , Ph
It is shown that the first step in the
reactions of the carbanionic nucleophiles
with chloroacetylenephosphonatesis is
substitution of chlorine with formation of
functionalized phosphonates. With
acetylacetone reaction affords K-derivative
of acetylacetone phosphonoacetylene
derivative. With dimedone, neutral product
of substitution is formed exerting prototropic
isomerization into allenic isomer. Monitoring
the same reaction with malonic dinitrile by
means of NMR spectroscopy showed
intermediate formation of both acetylenic and
allenic compounds followed by addition of
second molecule of the nucleophile with
formation of phosphonate tetranitrile
as a K-derivative.
79
K CO
2 3
P
O
KH
OH2
Tetramethyl acetylenediphosphonate + malonic
dinitrile + K2CO3: x-ray crystallography
Reaction with malonic esters affords a mixture of acetylenic and allenic compounds.
Reaction of the nucleophiles with acetylenediphosphonates proceeds as addition at the triple bond,
but in contrast to the similar reaction with acetylenedicarboxylates, this addition results in formation
of stable enough K-derivatives, as evidenced by NMR spectroscopy and x-ray
crystallography. Acidification by trifluoroacetic acid gives neutral compounds which enter
prototropic isomerization.
Reference
1. N. G. Didkovskii, A. I. Petryanina, A. V. Dogadina, and B. I. Ionin, Rus. J. Gen. Chem., 2006, Vol. 76, No.9, p. 1512,
1516.
2. A.M. Shekhadeh, N. G. Didkovskii, A. V. Dogadina, and B. I. Ionin, Rus. J. Gen. Chem., 2005, Vol. 75, No.1, p. 9.

P-75
THE PHOSPHO-ALDOL REACTION AND COMPLEXES OF ALUMINIUM
CONTAINING SALCYAN AND RELATED LIGANDS
Nichola E. Cosgrove and Terence P. Kee
School of Chemistry, University of Leeds, Woodhouse Lane, Leeds, LS2 9JT, UK
The phospho group is one of the most important biochemical functions, controlling many
biological processes such as cell membrane synthesis, signal transduction, energy conversion and
skeletal construction. The transfer of a phospho group known as phosphorylation, results in the
formation of a [P-O] linkage. A variation on this concept is hydrophosphonylation, where a
phosphorus-carbon bond is formed. One of the most versatile of the phosphorus-carbon reactions
is the phospho-aldol reaction (PA; Scheme below).
O
R P
O H
O
R
CAT CAT
H
O
X
R P
O H
O
R
R' H
R = alkyl, aryl etc. CAT = Catalyst; X = O
R
NH HN
XH n H nX
Salcyan
80
O
R P
O
O
R R'
X = O, n = 1; X = N, n = 2. R = H, Me, t Bu, Ph
X
H +
R
O
P
O
O
R R'
XH
The phosphonate group is very similar to those present in biological phosphates, allowing it the
ability to mimic their roles. In order to be successful in these applications, control over asymmetry
is vital as this could have severe repercussions upon the properties and effects it has on the body.
In this contribution, we outline some of the results of our molecular and electronic
(semi-empirical) modelling at the PM3 level using the Hyperchem 7.0 package (Hypercube, Florida)
combined with synthetic work on new types of ligand based on the salcyan framework.
Applications in PA catalysis are discussed.
R

P-78
SYNTHESIS OF 2-SUBSTITUED-PYRANO[2,3-D]PYRIMIDIN- 4(3H)-ONE
DERIVATIVES USING IMINOPHOSPHORANE
Qing-Yun Ren, Hong-Wu He*
Key Laboratory of Pesticide &Chemical Biology, Ministry of Education, College of Chemistry, Central China Normal
University, Wuhan, 430079, P. R. China
The derivatives of pyranopyrimidines have been the focus of great interest over many years. This
1, 2
is probably due to the fact that pyranopyrimidine system shows remarkable biological properties.
Here we reported the synthesis of 2-substituted-5-aryl-3,8-diphenyl- 6-methyl-5,8-dihydro-5H
-pyrazolo[4’,3’:5,6]pyrano[2,3-d] pyrimidin-4(3H)-ones 6. The pyrazolo[3,4- b]pyrimidine 3, easily
obtained from pyrazolone 1, ethyl α-cyanocinnamates 2 using TEBA as catalyst, was converted to
iminophosphorane 4 via reaction with triphenylphosphine, hexachloroethane and Et3N.
Iminophosphorane 4 reacted with phenyl isocyanate to give carbodiimides 5, which were allowed to
react with nucleophiles such as amines, alcohols and phenols to produce target
compounds.Structure of compounds 6 were identified by 1 H, IR spectral data, elementary analysis,
and x-ray analysis.
H3C Ar CN
H3C Ar
N
N
Ph
1
O
+
H
2
COOEt
H2O N
N
Ph
O
3
PhNCO
H3C
Ar
N N
Ph
5
O
COOEt
N
C NPh
81
HY
Base
H 3C
Y=NHR 1 , NR 2 2, OR 3 etc
SCHEME 1
COOEt
NH2
Ph3P
Ar
N N
Ph
6
H3C
O
N O
N
Ph
4
O
Ph
N
N
Ar
Y
COOEt
N PPh3
Acknowledgements
We gratefully acknowledge financial support of this work by National Key Basic Research
Development Program of China (No: 2003CB114406) and National Natural Science Foundation of
China ( No: 20372023).
References
[1] S. C. Kuo, L. J. Huang, and H. Nakamura, J. Med. Chem. 27, 539 (1984).
[2] R. Wriggleworth, W. D. Inglis, D. B. Livingstone, C. J. Snekling, and H. C. S. Wood, J. Chem. Soc Perkin Trans. 1.
959 (1984).

P-81
SYNTHESIS OF SOLANESYL PHOSPHONATE
Qu Lingbo 1 Shi Xiaona 2 Chen Xiaolan 2*
1 Anyang Normal University, Henan Province, Anyang, 455002, P. R. China
2 Department of Chemistry, Zhengzhou University, Zhengzhou, 450052, P. R. China
Solanesol, a long-chain terpenoid alcohol mainly existing in tobacco leaves, is the starting
material for many high-value biochemicals, including Vitamin K analogues and co-enzyme Q10
which is useful in the treatment of heart diseases, cancers and ulcers. Solanesol itself can be used as
cardiac stimulant, lipid antioxidant and antibiotics, and clinical trials are also developing the use of
solanesol as an anti-cancer drug [1] . Phosphonates have important applications in flame retardancy,
organic synthesis, and biological applications [2] . In the work described in this paper, three solanesyl
phosphonates were synthesized using standard Arbuzov [3] action, and their structures were
determined by ESI-MS, NMR and IR.
solanesol
7
OH
PBr3
P(OR)3
O
P OR
OR
7
a R= -CH3 b R= -CH2CH3 c R= -CH(CH3)2
Scheme 1. Synthesis of solanesyl phosphonates
References
[1] M. Wang, Integr. Util. Chines. Resour. 2003, 2, 16.
[2] Q. Yao, S. Levchik. Tetra. Lett. 2006,47:277-281.
[3] Bhattachary, A.K, Thyarajan. G. Chem. Rev. 1981,81,415.
82
7
Br

P-86
SYNTHESYS AND STRUCTURAL PECULIARITIES OF PHOSPHORUS
PENTACHLORIDE COMPLEXES WITH 4-DIMETHYLAMINOPYRIDINE AND
N-METHYLIMIDAZOLE
S.E.Pipko, L.V.Bezgubenko, A.D.Sinitsa, E.G.Kapustin, E.B.Rusanov, M.I.Povolotskii
Institute of Organic Chemistry, National Academy of Sciences of Ukraine, Murmanska 5, 02094, Kyiv-94, Ukraine
Coordination chemistry of non-metals still remains a little-studied field. In particular, literature
data on phosphorus complexes are rather controversial. We have recently studied the interaction of
phosphorus pentachloride with 4-dimethylaminopyridine (DMAP) and N-methylimidazole (NMI)
as some of the most effective N-donor ligands. The complexes [PCl4(DMAP)2] + Cl - (δ 31 Р -196 ppm.)
(1a) and [PCl4(NMI)2] + Cl - (δ 31 Р -231 ppm.) (1b) were isolated and investigated. Both complexes
react with H2O, EtOH or Et2NH very slowly. The relative hydrolytical stability of complexes
PCl4L2 + Cl - makes them useful condensing agents. We have found that they are highly effective in
the amide synthesis from carbonic acids and amines.
N
2
N
N
Cl Cl
N P N
Cl Cl
N
1a
Fig.1Fig.1
PCl 5
83
+ Cl-
N
2
N
N
N
Cl
P
Cl
Cl N
Cl
Fig. 1
Molecular and crystal structure of 1b was determined by X-ray single crystal diffraction. It was
found that the molecule of 1b has cis-orientation of NMI substituents (Fig.1) instead of the less
sterically hindered trans-orientation. In the cationic part of the complex the phosphorus atom has
four P-Cl bonds within the range 2.109-2.148Å, two P-N bonds (1.811 and 1.832 Å) and exhibits
slightly distorted octahedral coordination with the angles at phosphorus atom in the range of
87.57-91.50º. Two N-methylimidazole ligands are planar with the dihedral angle between them of
59.6 o . The number of the short CH•••Cl contacts of the hydrogen atoms of N-methylimidazole with
chlorine anion within the range of 2.65-2.85 Å have been found in the solid state. Six of the seven
H•••Cl contacts have ‘chelate’-like nature that can strongly stabilize crystal topology of cis-isomer.
This hypothesis was studied by DFT (B3LYP) calculations of cis- and trans-forms of 1a and 1b.
For both cations trans-form is more preferable (ca. 6.4-6.45 kcal/mol). At the same time
calculations of both cations with the Cl - anion show specific interactions between the anion and the
hydrogens of heterocyclic moiety making the cis-form more stable (ca.15.8 –15.9 kcal/mol).
1b
N
+
Cl -

P-87
CHEMISTRY OF FULVENE-TYPE P-HETEROCYCLIC COMPOUNDS
Shigekazu Ito, Hideaki Miyake, Satoshi Sekiguchi, Matthias Freytag, Masaaki Yoshifuji †
Department of Chemistry, Graduate School of Science, Tohoku University, Aoba, Sendai 980-8578, Japan
1,3,6-Triphosphafulvene 1 was isolated as a formal trimer of a phosphanylidene carbenoid
[Mes*P=CBr–Li: Mes* = 2,4,6-t-Bu3C6H2] and showed similar electrophilic reactivity to fulvene
[1]. Indeed, alkyllithium nucleophiles react at the exo P atom of 1 to afford the corresponding
cyclic anions 2. Alkylation of 2 with an alkyl halide showed regioselective P-alkylation to give
1H-[1,3]diphospholes 3 [2]. On the other hand, protonation of 2 unexpectedly afforded P-H
phosphorus ylides 4 [3]. The X-ray structure of 5 suggests unusual stability in air and moisture at
room temperatures. Additionally, we succeeded in isolation and structure elucidation of tricyclic
compound 6 as an isomer of 1 [4].
Mes*
P
P
1
Mes*
P
Mes*
Mes*
R
P
P
Mes*
P
Mes*
Mes*
2
Mes* = 2,4,6-t-Bu3C6H2 R
P
P
3
Mes*
P
R'
Mes*
84
R Mes*
P
H
Mes*
P
P
Mes*
4: R = alkyl
5: R = F
Mes*
t-Bu P
P
1,4-Diphosphafulvene 7 was obtained as a formal [3+2] cyclodimer of phosphaallene and its redox
property was studied by its cyclic voltammetry. Compound 7 with electron-donating character
formed a CT complex with TCNQ (7,7,8,8-tetracyanoquinodimethane) [5]. Chalcogenization of 2
afforded the monochalcogenized products 8 (E = O, S),
Ph
Ph
suggesting regioselective chalcogenization at the
sterically less-hindered phosphorus atom as well as E/Z
Mes*
P P
Mes* Mes*
P
E
P
Mes*
isomerization around the exo C=C bond [6].
Ph
7
Ph
8
Mes*
† Present address: Department of Chemistry, the University of Alabama, Tuscaloosa 35487-0336, USA.
Reference
[1] S. Ito, H. Sugiyama, M. Yoshifuji, Angew. Chem. Int. Ed. 2000, 39, 2781.
[2] S. Ito, H. Miyake, H. Sugiyama, M. Yoshifuji, Tetrahedron Lett. 2004, 45, 7019.
[3] S. Ito, H. Miyake, M. Yoshifuji, T. Höltzl, T. Veszprémi, Chem. Eur. J. 2005, 11, 5960.
[4] S. Ito, H. Miyake, H. Sugiyama, M. Yoshifuji, Heterocycles 2004, 63, 2591.
[5] S. Ito, S. Sekiguchi, M. Yoshifuji, J. Org. Chem. 2004, 69, 4181.
[6] S. Ito, M. Freytag, S. Sekiguchi, M. Yoshifuji, Sci. Rep. Tohoku Univ. 1st Ser. 2004, 81, 17.
P
6
E = O, S
t-Bu
t-Bu

P-89
SYNTHESIS AND COMPLEXATIONS OF A NOVEL STABLE CARBENE BEARING A
PHOSPHORUS YLIDE
Shin-ya Nakafuji, Junji Kobayashi, and Takayuki Kawashima
Department of Chemistry, Graduate School of Science, The University of Tokyo
7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
Since the first report by Arduengo in 1991, N-heterocyclic carbenes (NHCs) have been
extensively studied. Due to their successful application as ligands for transition metal catalysts, the
tuning of electronic and structural properties of NHCs has become an important subject. One of the
modification of NHCs is changing amino groups adjacent to the carbene center to other -donating
substituents. Thus, we focus our attention on carbene 1, which has a phosphorus ylide moiety.
Because -donation of the ylide carbanion to the carbene center is almost same as an amino group
and electronegativity of carbon is smaller than that of nitrogen, 1 is expected to exhibit a strong
-electron donating ability to transition metals. Although several transition metal (Pt, Cr, Mo, W)
complexes of carbene 1 (R = H) were reported 1) , they were synthesized from the corresponding
isocyanide complexes, and available metals were also limited. In this report, we will present
exploitation of general synthetic method of carbene 1 (R = CH3) and its complexation.
Reaction of phosphonium salt 2 with mesityllithium gave a mixture of 2, carbene 1 ( P 10), and
diphenylphosphine 3. Diphenylphosphine 3 seems to be formed by 1,3-phenyl shift of carbene 1
during treatment of the reaction mixture. At lower temperature, however, carbene 1 was able to be
trapped by elemental sulfur to give 4 quantitatively.
To evaluate the ligand property of carbene 1, rhodium complexes 5 and 6 were prepared. Both 5
and 6 didn’t show any decomposition in the course of work up with water. In the infrared spectrum,
carbonyl stretching frequencies of 6 were observed at the lowest wave numbers among analogous
carbene rhodium complexes, indicating that carbene 1 has a strong -donating ability.
PPh 3
N
R
1
Ph 3P
N
CH3 2
Ph 4B
PPh 2
Ph
N
CH3 3
85
PPh 3
S
N
CH3 4
PPh 3
M
N
CH3 5 (M = Rh(cod)Cl)
6 (M = Rh(CO) 2Cl)
Reference
1) Michelin, R. A.; Pombeiro, A. J. L.; Guedes da Silva, M. F. C. Coord. Chem. Rev. 2001, 218, 75.

P-91
AN EFFICIENT SYNTHESIS OF α-(SUBSTITUTED PHENOXY ACETOXY)ALKYL
PHOSPHINATES SODIUM SALTS
Tao Wang 2 , Hong Wu He 1*
1.Institute of Pesticide Chemistry, Central China Normal University, Wuhan, 430079 P.R.China
2. College of Chemistry and Chemical Engineering, Jiangxi Normal University, Nanchang, 330022, P.R.China
One approach to design a inhibitor of Pyruvate dehydrogenase(PDH) with a novel structure by
using biochemical reasoning was attempted. A series of α-(substituted phenoxyacetoxy) alkyl
phosphinic acid methyl ester I and its corresponding phosphinate salts II were synthesized as
potential inhibitor of PDH. The title compounds can be prepared from α-( substituted phenoxy
acetoxy) alkyl phosphinic acid methyl esters I which were synthesized by the condensation of
methyl α -hydroxyalkyl phosphinates with substituted phenoxyacetic chloride. This method
provide a simple and efficient procedure for the synthesis of phosphinate derivatives containing
sensitive groups to acid, base or water such as carboxylate ester. The formation of the title
compounds II can be rationalized in terms of direct reaction of the esters I with oven-dried sodium
iodide in the presence of molecular sieve (4A) in dried acetone under nitrogen for 4~6 hours. Some
advantageous features are: (a) the title compounds II can be obtained from I in one-step; (b) the
reactions only need short time under mild condition by a simple procedure. On the basis of this, the
herbicidal activity of title compounds was evaluated in a set of experiment in greenhouse. Most of
title compounds exhibited notable inhibitory activity to the growth of Echinochloa crusgalli (L.)
Beauv.,Digitaria adscendens, Medicago sativa L., Brassica napus and Amaranthus retroflexus.
O
H3C P
H3CO CH OH
R
Na I
CH3COCH3 N2 O
+ Cl CCH2O
O
H3C P
NaO
X
Y
O
CH O CCH2O R
II
(C 2H 5) 3N
DCM
O
H3C P
H3CO X
Y
86
CH O
R
O
CCH2O Acknowledgments
This work was supported by the National Basic Research Program of China (No: 2003CB114400) and the National
Natural Science Foundation of China (No: 20372023).
*Address correspondence to Hong-Wu He, Key Laboratory of Pesticide & Chemical Biology of
Ministry of Education, Central China Normal University, Wuhan 430079, People’s Republic of
China E-mail: hel208@mail.ccnu.edu.cn
I
X
Y

P-93
PHOSPHORYLACETIC ACID THIOAMIDES AS KEY SUBSTANCESFOR
PHOSPHORYLATED HETEROCYCLES
V.A. Kozlov, I. L. Odinets, D.V. Aleksanyan, P.V. Petrovskii, T. A. Mastryukova
A.N. Nesmeyanov Institute of Organoelement compounds RAS, Vavilova str.28, Moscow,119991 Russia.
E-mail: odinets@ineos.ac.ru
Rather often thioamides serve as building blocks to obtain heterocycles of pharmaceutical
importance. Recently we elaborated the facile synthetic route to phosphorus substituted carboxylic
acid thioamides 1 and demonstrated their application in regioselective heterocyclization with
dimethylacetylendicarboxylate leading to phosphorus containing thiazolidin-4-ones as potential
drug-candidates. 2 Here we would like to demonstrate the ability of the above mention substrates to
play a role of annelating reagent in the reaction with quinoxaline derivatives. As azines containing
two and more heteroatoms undergo annelation with thioamides to yield annulated heterocycles
possessing biological activity we investigate the reactivity of phosphorylated thiamides in such
reactions.
It was found out that interacting with 2,3-dichloroquinoxaline starting phosphoruscontaining
substrates served as thionation agents resulting in bis(quinoxalinil)sulfide and
phosphorylacetonitrile instead of the expected thiazolo[4,5-b]quinoxaline.
N Cl
N
Cl
(EtO) 2P(O)CH 2C(S)NH 2/2Et 3N
87
N Cl
N
S
Cl
(EtO) 2P(O)CH 2CN
Despite the interaction with N-methylqunoxalinium iodide proceeded as annelation, it resulted in
3-phosphorylated thiolactames – 3-phosphoryl-tetrahydroquinoxalino[2,3-b] -pyrrolidin-2-thiones
in contrast to the similar reactions of non-phosphorylated thioamides giving thiazole derivatives.
N
N
CH 3
I Et 2NH/EtOH
N
N
CH 3
H
OEt
R 2P(O)CH 2C(S)NH 2
R=OEt, Ph
The structure and NMR features of the compounds obtained will be discussed as well the reasons
of such difference in reactivity of phosphorylated and non-phosphorylated thioamides.
Financial support: Russian Basic Research Foundation (grant 05-03-32692)
References
1. V.A.Kozlov, I.L.Odinets, K.A.Lyssenko, S.G.Churusova, S.V.Yarovenko, P. V. Petrovskii and T. A. Mastryukova. Izv.
AN, Ser. khim., 2004, 4, 887-893 (Russ.Chem.Bull., 2004, 53(4), 925-931)
2. V.A. Kozlov, I. L.Odinets, K. A.Lyssenko, S. G.Churusova, S. V.Yarovenko, P.V.Petrovskii, T.A.Mastryukova,
Heteroatom Chem., 2005, 2, 159-168
+
N
N
N
N
CH3
N
S
PR 2
O

P-94
THE FORMATION OF ION-RADICAL SALTS IN THE REACTION OF FULLERENE
C60 WITH PHOSPHORUS (III) AMIDES
I.P.Romanova, V.F.Mironov, G.G.Yusupova, О.А.Larionova,
V.I.Morozov, O.G.Sinyashin
A.E.Arbuzov Institute of Organic and Physical Chemistry, Kazan Research Centre of Russian Academy of
Sciences, Arbuzov Str. 8, Kazan, Russia 420088, E-mail: romanova@iopc.kcn.
Since the discovery of fullerene С60 it has been intensively studied as electron-withdrawing
component of donor-acceptor dyads using for the creation of the molecular devices. It is known that
such phosphorus donors as white phosphorus (P4) and phosphine oxides 1,2 form the molecular
complex with С60. The phosphines are easily oxidized in presence of С60. The phosphine complexes
with BH3 add to the fullerene moiety with the formation of the fullerene C60 acyclic derivatives 3 .
Here the results of the fullerene interactions study with strong nucleophiles such as hexamethyl- and
hexaethyltriaminophosphines 1 and 2 are discussed.
1, 2
C60
5, 6
hν
1O2
O2
3C60
7, 8
R = Me (1, 3, 5, 7), Et (2, 4, 6, 8)
P(NR2)3
O=P(NR2)3
7, 8
1O2
1, 2
C60 P(NR2)3
3, 4
1O2
C60
+
P(NR2)3
+
P(NR2)3
5, 6
88
_
C60
-C60
C60
-C60
+
P(NR2)3
A
+ +
(R2N)3P P(NR2)3
B
A - (1, 2)
C60
+
P(NR2)3
+
P(NR2)3
C
Using the ESR, NMR 31 Р and UV-spectroscopy it was shown that fullerene C60 forms the
ion-radical salts 3 and 4 with phosphites 1 and 2. These salts are unstable. Firstly, they are oxidized
to amidophosphates 7 and 8. Secondly, they undergo the further transformations to the new
ion-radical salts 5 and 6. The triads 5 and 6 are also unstable and gradually convert into diamagnetic
compounds 7, 8 and fullerene oxides. The formation of triads 5, 6 is supposed to involve the
intermediate formation of the strong electrophilic dication В. Financial support from RFBR (grant
no. 05-03-32418) and OCCM Program no.7 is gratefully acknowledged.
References
[1] R.E.Douthwaite, M.L.H.Green, S.J.Heyes, M.J.Rosseinsky, J.F.C.Turner. J. Chem. Soc., Chem. Commun., 1994, 11,
1367.
[2] S.Bhattacharya, S.Banerjee, S.K.Nayak, S.Chattopadhyay, A.K.Mukherjee. Spectrochimica Acta, Part A. 2004, 60,
1099.
[3] S.Yamago, M.Yanagawa, H.Mukai, E.Nakamura. Tetrahedron. 1996, 52, 5091.

P-95
NEW METHOD FOR THE ASYMMETRIC REDUCTION OF KETOPHOSPHONATES
Vitaly V. Nesterov, Oleg I. Kolodiazhnyi
Institute of Bioorganic Chemistry and Petrochemistry, National Academy of Sciences of Ukraine, Murmanskaia 1, Kyiv,
UKRAINE e-mail: oikol123@rambler.ru
The chiral reducing reactants (S)-1 or (R)-1 were prepared from lithium, sodium or
tetrabutylammonium borohydrides and (S)- or (R)-tartaric acids [1,2].
HO
HO
O
O
H B H M+
O
-
HO
HO
O
O
S-1 R-1
89
O
O
H B H M +
O
-
M= Li, Na, Bu4N The reduction of - or -ketophosphonates with (S)- or (R)-1 leads stereoselectively to the
formation of (R)-, or (S)- - or -hydroxyphosphonates, correspondingly, in high yields and very
good stereoselectivity.
The stereoselectivity of reaction depended on the absolute configurations of 1 and
ketophosphonates. The reduction of di(1R,2S,5R)-menthyl ketophosphonates with the (R)-1
proceeded with matched double asymmetric induction to give high enantiomeric excesses of
hydroxyphosphonates (up to >96 % ee). The methodology was used for the preparation of
enantiomericly pure phosphonate modified carnitine and other biologically active phosphonic acids
in multigram scale.
(RO) 2P(O)(CH2 ) n
(R)-3, 4
R'
H
OH
1) (S,S)-1
2) H3O (RO) 2P(O)(CH 2 ) n
2
R'
O
1) (R,R)-1 R'
H
HO
(CH2 ) nP(O)(OR) 2
(S)-3, 4
TA - Tartaric Acid
+ 2) H3O +
, R=Et, Mnt (3), H (4)
Asymmetric reduction of ketophophonates with reagent (S)-1 or (R)-1 (R’O)2P(O)(CH2)nCH(OH)R
R R’ N ТА YIELD, % EE (OR DE),% CONFIG
CH2CL MNT 1 R,R 93 96 S
CH2CL ET 1 R,R 82 80 S
PH ET 0 R,R 95 60 S
PH MNT 0 R,R 95 92.5 S
PH MNT 0 S,S 98 46 R
PH ET 0 S,S 94 60 R
2-FC6H4 MNT 0 R,R 97 82 S
2-AN MNT 0 R,R 96 74 S
PYPERONY
L
MNT 0 R,R 97 96 S
References
1 V. V. Nesterov and O. I. Kolodiazhnyi Tetrahedron: Asymmetry 2006, 17, 1023-1025
2 O. I. Kolodiazhnyi Tetrahedron: Asymmetry 2005, 16, 3295-3340

P-96
DIASTEREOSELECTIVE SYNTHESIS OF ENANTIOPURE CYCLIC α-
AMINOPHOSPHONIC ACIDS
Vladimir A. Alfonsov 1 , Charles E. McKenna 2 , Еvgenia V. Bayandina 1 , Boris Kashemirov 2 ,
Liliya N. Yarmieva 1 , Olga N.Kataeva 1 , Lyudmila N.Punegova 1 .
1 A.E.Arbuzov Institute of Organic and Physical Chemistry, Kazan Scientific Centre of the
Russian Academy of Sciences, 420088, Arbuzov Str., 8, Kazan, Russian Federation. Fax: +78432 75 5322; E-mail:
alfonsov@iopc.knc.ru
2 Department of Chemistry, University of Southern California, Los Angeles, CA 90089 USA
The reaction of dialkylchlorophosphites with β-aldiminoalcohols proceeds by intramolecular
cyclization with formation of 1,4,3-oxazaphosphorine derivatives. Imines containing an asymmetric
center in the parent β-amino alcohols give rise to a new chiral center at position 3 of
oxazaphosphorine ring with very high diastereoselectivity, resulting in a non-equal mixture of the
two diastereomers A and B, which are distinguished only by their phosphorus atom configuration.
Thus, we have found the new and efficient way of synthesis of cyclic aminophosphonic acids by the
reaction of dialkylchlorophosphites with β-aldiminoalcohols.
The well-known obtention of free phosphonic acids from the corresponding dialkyl esters by
silyldealkylation with trimethylbromosilane provides in enantiopure form, the cyclic
aminophosphonic acids as HBr salts.
This work was supported by the Civilian Research and Development Foundation (grant no. RUC2-2638-KA-05) and
the Russian Foundation for Basic Research (grant no. 03-03-33082).
90

P-100
STUDIES ON THE SYNTHESIS AND SEPARATION OF ISOLEUCINE
OLIGOPEPTIDES ASSISTED BY PHOSPHORUS OXYCHLORIDE
Wei-Na CAO 1 ,Li-Na TANG 1 ,Li MA 1 ,Kui LU* 1 ,Yu-Fen ZHAO 2
1.Department of Chemistry and Chemical Engineering, Henan University of Technology, Zhengzhou 450052;
2.Department of Chemistry, Xiamen University, Xiamen 361005, China
The 21st century is a century of life sciences, the substances with bio-activities have gained
significant attraction, including oligopeptides[1]. Obviously, the synthesis and separation of
oligopeptides have become a hotspot of research[2]. In this paper, the reaction of self-assembly into
isoleucine oligopeptides from L-isoleucine with the assistance of phosphorus oxychloride was
studied by using ESI-MS, and the separation methods for isoleucine oligopeptides library were also
researched, the pure Ile-Ile was separated under the optimized conditions by using RP-HPLC. The
results suggested that the suitable condition of direct synthesis was: the molar ratio of L-Ile and
POCl3 of 1 to 1, the temperature 50℃, the solvent dioxane, reaction time 2h, and the Ile-Ile was
characterized by ESI-MS/MS.
Acknowledgements: The authors would like to thank the financial supports from the Chinese
National Science Foundation (No.20272055, 20572016), Henan Province Science Foundation for
Prominent Youth (No.0312000900) and Office of Education of Henan Province (No.
2006KYCX017, 200510459015).
References:
1. Westheimer F.H., Science.1987, 235(4973): 1173~1178.
2. Lu, K.; Liu, Y.; Zhou, N.; Chen, Y.; Feng, Y.-P. ; Guo, X.-F.; Chen, W.; Qu, L.-B.; Zhao, Y.-F. Acta Chim. Sinica
2002, 60, 372 (in Chinese).
91

P-101
SYNTHESIS OF BIS(PHOSPHONATES) PYRROLIDINES DERIVATIVES
Feng Gao, Ting-ting Wang, Ying-jun Song, Wen-hu Wang*
Institute of Elemento-Organic Chemistry, Nankai University, Tianjin, 300071,China
The cycloadditon of azomethine ylides with electronic-deficient olefins provides an efficient
method for synthesizing substituted pyrrolidines contained in many biologically active
compounds. [1] Many works have been done in this field in recent years. However, few results have
been reported about the reaction of azomethine ylides with vinylphosphonates. [2] We present herein
our results on the reaction between in situ generated azomethine ylides 2 and tetraethyl
vinylidenebis(phosphonates) 3.
N-Metallated azomethine ylides 2 were generated by the reaction of arylidene imines 1 with
AgOAc and triethylamine.These azomethine ylides undergo cycloaddition to 3 at room temperature
with good regioselectivity and yields. The main product is compound 4. The structure of the two
cycloadducts were confirmed by 1 H NMR, 31 P NMR and elemental analysis.
Reference
[1] Gribble, G. W. In Comprehensive Heterocyclic Chemistry; Katritzky, A. R., Rees, C. W., Scriven, E. F. V., Eds.;
Pergamon: Oxford, U.K., 1996; Vol. 2, pp 207-257.
[2] Jesùs, C. Ronald, G. etal,. Eur. J. Org. Chem. 2001, 1971-1982.
92

P-104
SYNTHESIS OF NOVEL BICYCLI CAGED PHOSPHATE DERIVATIVES
Wen-Yan MO, Hong-Wu HE*
Key Laboratory of Pesticide & Chemical Biology of Ministry of Education,
Central China Normal University, Wuhan 430079, People’s Republic of China
E-mail: hel208@mail.ccnu.edu.cn
A series of novel bicyclic caged phosphates, containing α-substituted alkyl phosphonates have
been synthesized. The precursors of α-substituted alkyl phosphonates 1 were obtained by
dropping dimethylphosphite to aldehydes soultion in ice bath(0~5℃). Pentaerythritol reacts with
POCl3, leading to preferable formation (87~95%) of 1-hydroxymethyl-4-phospha-3,5,
8-trioxabicyclo[2,2,2]octane 2, which affords the corresponding acid 3 via oxidation using NH4VO3
as catalyst. 3 was easily acylated by α-substituted alkyl phosphonates 1 to give bicyclic caged
phosphates derivatives 4 with moderate or good yields. The structures of all title compounds were
confirmed by IR, 1 H NMR,MS spectra and elemental analysis.
O
H3CO Et3N O
P H + RCHO
H3CO H
H3CO CH2Cl P C R
2 H3CO OH
1
C(CH 2OH) 4
POCl 3
1. SOCl2 2. CH2Cl2, Et3N, 1
O
O
O P
O
2
O
O
O P
O
4
CH 2OH 65% HNO 3
NH 4VO 3
O
C
O H C
R
93
O
OCH3
P
OCH3 O
O
O P
O
3
COOH
R=CH 3, furyl,
(un)substituted phenyl
Acknowledgments
Financial support by National Basic Research Program of China (2003CB114400) and NNSFof China ( 20372023)
References
[1] Verkade, J.G.; Reynold, L., J.Org.Chem. 25,633(1960).
[2] Ozoe, Y.,Mochida, K., Eto, M., Agric. Biol. Chem., 46,2521(1982)
[3] Ratz, R.F.W., US 3168549,1965
[4] Ratz, R.F.W., US 3287448,1966
[5] Scriven, Eric, F. V., Chem.. Soc. Rev., 12,129(1983)
[6] Yu-Gui LI, Jian-Ji WANG, Tao HAN , Acta Chim. Sinica, 46,679(1988).
[7] Yu-Gui LI, Xin-Long WANG, Xue-Feng ZHU, Chin. J. Org. Chem. 15,57(1995)
[8]Yu-Gui LI, Xue-Feng ZHU, Qin WANG., Chem. J. Chin. Univ., 17,1394(1996)

P-106
THE SYNTHESIS AND REACTIONS OF ALKYL
2,3,3-TRIS(DIALKOXYPHOSPHORYL)PROPIONATES AND ALKYL
2,3,3-TRIS(DIALKOXYPHOSPHORYL)ACRYLATES
Yuen-Ki Cheong, Philip Duncanson, D. Vaughan Griffiths and Xiao Han
School of Biological and Chemical Sciences, Queen Mary, University of London
Mile End Road, London, E1 4NS, UK
We have previously reported the preparation of novel ylide bisphosphonates such as 2 from the
reaction of dichloromaleic anhydride 1 with trialkyl phosphite.[1] We have now investigated the use
of these and related system as precursors for the preparation of some novel bis- and
tris-phosphonates.
RO O
P
O
O
(RO) 2P
(RO) 2P O
O
OR
RO O
P
RO
HCl
O
ROH
O
DCM (RO) 2P
(RO) 2P O
2
O
O
O
Cl
(RO) RO
3P
O
Cl
P
O
1
3
4
OR
O O
RO
P
RO
OR
RO
P
RO OR
O O
Conversion of the ylide 2 to the trisphosphonate 4 can be readily achieved either via the anhydride
3 or directly by heating 2 under reflux with the appropriate alcohol. Conversion of this
trisphosphonate 4 to the corresponding acrylate is illustrated below for the case R=Et. Thus,
deprotonation of 4 (R=Et) by the action of a base (such as EtONa or NaH) gave the chelate 5 (R=Et),
which on treatment with bromine in the presnce of excess base underwent bromination and then
elimination to give the acrylate 6 (R=Et).
P
4 (R=Et) 5 (R=Et) 6 (R=Et)
OEt
O O
EtO
P
EtO
OEt
EtO
P
P
EtO OEt
O O
OEt
Na
O O
EtO
EtONa
P
EtO
OEt Br2 EtO
P
P
EtO OEt
O O
OEt
O O
EtO
P
or
EtO
OEt
NaH
EtO
P
EtO OEt
O O
δ P 22.3 (d, J = 7 Hz)
22.4 (dd, J = 57, 7 Hz)
23.0 (d , J = 57 Hz)
δ P 27.3 (d , J = 17 Hz, P-C-P)
36.8 ( t, J = 17 Hz)
94
δ P 5.8 (1 P, dd, J = 83, 37 Hz)
9.1 (1 P, dd, J = 40, 37 Hz)
11.4 (1 P, dd, J = 83, 40 Hz)
The reactions of the trisphosphonates 3, 4, and 6 have been investigated and will be reported. The
reaction of 6 with benzylazides is of particular interest since it eventually results in the loss of one of
the phosphonate groups and the formation of a novel bisphosphonate. The structure of this compound
and its mode of formation will be discussed.
Reference
[1] P. Duncanson and D. V. Griffiths, icpc2004

P-112
REACTIONS BETWEEN N-(THIO)PHOSPHORYL IMINES AND DIETHYLZINC
Xinpeng Ma, Xinyuan Xu, Chungui Wang, Guofeng Zhao*, Zhenghong Zhou*, Chuchi Tang
State Key Laboratory of Elemento-Organic Chemistry, Institute of Elemento-Organic Chemistry, Nankai University,
Tianjin 300071, P. R. China
Asymmetric addition of imine is a convenient and practical method for the preparation of
synthetic valuable nitrogen-containing compounds, such as chiral amines, 1,2-diamines and α- or
β-amino acids. Recently, significant progress has been witnessed in this area. 1 Phosphoryl group
was one of the important N-protecting groups of imine. The asymmetric alkylation of
N-diphenylphosphinoylimines with diethylzinc could be run smoothly in the presence of chiral
copper catalysts or chiral 1,2-aminoalcohols. Since N-diphenylphosphinoylimines were the only one
N-phosphoryl imine used in asymmetric reaction, we plan to extend this substrate to more available
and cheap O,O-diethylphosphorylimine and its thio analogues.
It was interesting that the change of the substituent on phosphorus atom in N-phosphoryl imine
resulted in a total reversion of the direction of this reaction. The corresponding reduction product
rather than the alkylation product was obtained exclusively. Ethylene was released from the reaction
system at the same time. However, the addition of TMEDA, which has proven to be a strong
coordinating ligand to zinc, led to the reversion of the reaction orientation. The normal ethylating
product was obtained as the dominant product.
Acknowledgment
We are grateful to the National Natural Science Foundation of China (No. 20472033) for generous financial support for
our programs.
References
[1] (a) Kobayashi, S.; Ishitani, H. Chem. Rev. 1999, 1069. (b) Vilaivan, T.; Bhanthuranavin, W. Current Org. Chem.
2005, 9, 1315.
95

P-113
AZA-HENRY REACTION BETWEEN N-THIOPHOSPHORYL IMINES
AND NITROMETHANE
Xinpeng Ma, Xinyuan Xu, Chungui Wang, Guofeng Zhao*, Zhenghong Zhou*, Chuchi Tang
State Key Laboratory of Elemento-Organic Chemistry, Institute of Elemento-Organic Chemistry, Nankai University,
Tianjin 300071, P. R. China
The aza-Henry (nitro-Mannich) reaction, the nucleophilic addition of nitroalkanes to imines to
give α-nitroamine derivatives, is one of the most important tools for carbon-carbon bond formation
and has been used for the synthesis of a vast array of 1,2-diamines and α-amino acids, which are
valuable intermediates for the synthesis of many pharmaceutically active compounds. 1 Recently, we
discovered that thermal condensation of acetals and different types of thiophosphoramide could
conveniently afford N-thiophosphoryl imines in excellent yields with high purities. 2
These
N-thiophosphoryl imines are successfully employed as imine substrates in the aza-Henry reaction of
nitromethane.
The corresponding α-nitroamine derivatives 2 were obtained in almost quantitative yields in the
presence of a catalytic amount of N,N,N’,N’-tetramethylguanidine (TMG, 10 mol%) under
solvent-free conditions. The thiophosphoryl group in α-nitroamines 2 could be conveniently
removed through acidic hydrolysis and methanolysis. Moreover, 2 could be readily transformed to
1,2-diamines and α-amino acids via reduction or Nef reaction, respectively. Therefore, this
procedure furnishes a convenient and practical synthetic method for 1,2-diamines and α-amino
acids.
Acknowledgments
We are grateful to the National Natural Science Foundation of China (No. 20472033) for generous financial support for
our programs.
References
[1] Westermann, B. Angew. Chem. Int. Ed. 2003, 42, 151.
[2] Xu, X. Y.; Wang, C. G.; Zhou, Z. H.; Zeng, Z. B.; Ma, X. P.; Zhao, G. F.; Tang, C. C. Lett. Org. Chem. 2006, 3,
640.
96

P-114
ORGANOCATALYTIC ASYMMETRIC SYNTHESIS OF
α- HYDROXY PHOSPHONATES
Xinyong Li, Weiwei Jin, Caibao Chen and Wen-Jing Xiao*
Key Laboratory of Pesticide and Chemical Biology, Ministry of Education, College of Chemistry, Central China
Normal University, 152 Luoyu Road, Wuhan, Hubei 430079, China
wxiao@mail.ccnu.edu.cn
Quinine and its derivatives have been used as organocatalysts in asymmetric
hydrophosphonylation of aldehydes to synthesis α- hydroxy phosphonates. It was found that the
hydrophosphonylation reaction worked very well in the presence of 10 mol% Quinine. Asymmetric
synthesis α- hydroxy phosphonate also can be carried out using water as the reaction medium.
O
O
10mol%Quinine
EtO P
H R H
EtO
toluene rt
97
R
OH
*
P OEt
OEt
O
References
1) Davies, S. R.; Mitchell. M. C.; Cain, C. P.; Devitt, P. G.; Taylor, R. J.; Kee, T. P. J. Organometallic Chem. 1998,
550, 29.
2) Saito, B.; Katsuki, T. Angew. Chem. Int. Ed. 2005, 44, 4600.
O
HO
N
N

P-115
THE AZA-MORITA-BAYLIS-HILLMAN REACTION OF N-THIOPHOSPHORYL
IMINES CATALYZED BY 1,3,5-TRIAZA-7-PHOSPHAADMANTANE
Xinyuan Xu, Chungui Wang, Zhenghong Zhou*, Chuchi Tang
State Key Laboratory of Elemento-Organic Chemistry, Institute of Elemento-Organic Chemistry, Nankai University,
Tianjin 300071, Peoples’ Republic of China
In the reported aza-MBH reactions, tosyl and acyl are most often used as the imine’s
N-protecting groups, probably because their protected imines have better reactivities. In contrast,
N-phosphinoyl imine has been rarely used due to its troublesome preparation, although phosphinoyl
could be easily deprotected via acidic hydrolysis from the aza-MBH reaction adduct. Up to date,
there is only one report about the aza-MBH reaction of N-phosphinyl imines. 1 Recently, we
discovered that thermal condensation of acetals and different types of thiophosphoramide
conveniently led to the formation of N-thiophosphoryl imines in excellent yields with high
purities.2 Herein, we report the 1,3,5-Triaza-7-phosphaadmantane (PTA)-catalyzed aza-MBH
reaction of N-thiophosphoryl or N-thiophosphinoyl imines.
The reaction took place smoothly to give the corresponding aza-MBH adducts 2 in fair to
excellent yield. In addition, 2 could be easily deprotected through acidic hydrolysis or methanolysis.
Therefore, this protocol provides a convenient and practical synthetic method for versatile
intermediates α-methylene-β-amino ketone or acid derivatives.
Acknowledgments
We are grateful to the National Natural Science Foundation of China (No. 20472033) for generous financial support for
our programs.
References
[1] Shi, M.; Zhao, G. L. Tetrahedron Lett. 2002, 43, 4499.
[2] Xu, X. Y.; Wang, C. G.; Zhou, Z. H.; Zeng, Z. B.; Ma, X. P.; Zhao, G. F.; Tang, C. C. Lett. Org. Chem. 2006, 3,
640.
98

P-118
POLARITY AND CONFORMATIONS OF
1,2,4,5-TETRA(TERT-BUTYLPHOSPHA)CYCLOHEXANES IN SOLUTION
Ya.A. Vereshchagina, a, b E.A. Ishmaeva, b D.V. Chachkov, a A.A. Gazizova, a Z.S. Novikova
a
Kazan State Technological University, K. Marks St., 68, Kazan, 420015, and
b
Kazan State University, Kremlevskaya St., 18, Kazan, 420008, Russian Federation;
e-mail: yavereshchagina@yahoo.com
We studied polarity and spatial structure of 1,2,4,5-tetra(tert-butylphospha)-cyclohexanes 1, 2 by
the methods of dipole moments and quantum chemical calculations. Polarity of compounds 1, 2 was
determined in solution at 25°C, the coefficients of calculated equations and experimental dipole
moments are presented below.
t-Bu
t-Bu
X
P
P
P P
X
X
X
Bu-t
Bu-t
1 X = lone pair of electrons; 2 X = S
№ Solvent α γ Por, cm 3 µexpt, D
1 benzene 3.891 0.150 267.279 3.60
2 dioxane 8.582 0.369 685.899 5.76
Dipole moments of possible conformers of compounds 1, 2 were calculated using vector-additive
scheme and methods of quantum chemistry (program Gaussian 98, method B3LYP/6-31G* for 1;
program Priroda, method PBE/3z for 2).
P
P
t-Bu
t-Bu
Bu-t
Conformer
t-Bu
1a
P
P
P
Bu-t
Bu-t
ΔE, kcal . mole -1 7.33 0.00
µtheor, D 0.00 1.80
Conformer
t-Bu
t-Bu
P
P
Bu-t
P
1c P
Bu-t
ΔE, kcal . mole -1 5.45 4.93
µtheor, D 1.88 1.77
Four different conformations 1a-1d were found for cyclic derivative P III according to the data of
calculation. In all probability, the form of twisted chair 1b was energetically preferred in the
conformational equilibrium of asymmetrical chair conformations.
Chair form with trans-arrangement of identical substituents at the phosphorus atoms was
preferred in the conformational equilibrium for compound 2 (theoretical calculations of the ΔE and
dipole moments, the calculation of dipole moments using vector-additive scheme).
99
1b
1d
t-Bu
t-Bu
t-Bu
P
P
t-Bu
P
P
P
P
P
Bu-t
Bu-t

P-119
NOVEL IONIC PHOSPHINE LIGANDS: THEIR SYNTHESIS AND APPLICATION IN
SUZUKI COUPLING REACTION IN IONIC LIQUID
Yan Chen,Guang-Ao Yu*,Yong Ren,Xiang-Gao Meng,Jin-Tao Guan,Sheng Hua Liu
Key Laboratory of Pesticide & Chemical Biology, Ministry of Education, College of Chemistry,
Central China Normal University, Wuhan,,430074, China
The synthesis on phosphine ligand with cobaltocenium backbone was underdeveloped [1][2] .
Herein we report a general procedure for the synthesis of novel phosphine-substituted
cobaltocenium salts, and their usage as ligands for Suzuki coupling reaction in ionic liquid. 1,
1’-Bis(dicyclohexylphosphino) cobaltocenim hexafluorophosphate (di-cypc + PF6 - ) (1a),
1,1’-bis(di-iso-propylphosphino) cobaltocenium hexafluorophosphate (di-isoppc + PF6 - ) (2a),
1,1’-bis(di-tert-butylphosphino) cobaltocenium hexafluorophosphate (di-tbpc + PF6 - ) (3a), and the
monophosphine ligand Cc + PR2PF6 - (Cc + = cobaltocenium; R = Cy, 1b; R = i-Pr, 2b; R = t-Bu, 3b)
were synthesized and characterized by elemental analysis, spectroscopy, and X-ray crystal
diffraction techniques. These ligands were proved to be air-stable and suitable for Suzuki coupling
reaction in ionic liquid 1-butyl-3-methylimidazolium hexafluorophosphate (BMIM + PF6 - ), owing
high catalytic activity.
NaCp + ClPR2 1. n-BuLi
2.CoCl2 3.C2Cl6 Co + Cl -
PR 2
PR 2
+
Co + Cl -
PR2 100
NH 4PF 6
Co + PR2 PF -
6
PR 2
1a R= Cy
2a R= i-Pr
3a R= t-Bu
+
Co + PR2 - PF6 1b R= Cy
2b R= i-Pr
3b R= t-Bu
References
1) Brasse, C. C.; Englert, U.; Salzer, A.; Waffenschmidt, H.; Wasserscheid, P. Organometallics 2000, 19, 3818.
2) Song, L.-C.; Yu, G.-A.; Su, F.-H.; Hu, Q.-M. Organometallics, 2004, 23, 4192.

P-120
SYNTHESIS AND CHARACTERIZATION OF NOVEL BILE ACIDS DERIVED
H-PHOSPHONATES CONJUGATES
Yan Li, Yong Ju, * Yufen Zhao
Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology, Ministry of Education, Department of
Chemistry, Tsinghua University, Beijing 100084, P. R. China, Email: juyong@tsinghua.edu.cn,
Bile acids are natural origin compounds and play a very important role in biological systems. The
medicinal applications of bile acids and their conjugates were reported in numerous literatures 1,2 .
Such as, antiviral and the antifungal properties 3-5 and as carriers of liver-specific drugs, absorption
enhancers and as cholesterol level lowering agents 6,7 . Besides their biological importance, the
amphiphilic properties, the rigid concave of the backbone and the unique disposition of hydroxyl
groups on the one side of the molecule make these compounds attracting building blocks for the
design of synthetic receptors 7,8 . Bile acids have also been introduced to polymers that may lead to
the development of new biocompatible materials 9,10 . Here, the H-phosphnates of bile acids
conjugated with alcohols and nucleosides were synthesized in “one pot” reaction. The structures of
these novel bile acid conjugates were confirmed by IR, 31 P NMR, 1 H NMR and HRMS and the
NMR spectra.
OH
OH
OH
O
OCH 3
i
O
O PH
O
O O
O
HP
HP
O
O
O
101
O
OCH 3
ii
iii
O
O PH
O
O PH
O
O
O
PH
O
O O
O PH
O
O
PH
O O O
PH
O
O
Project supported by the NSF of China (No. 20542004) and SRFDP of Higher Education (No.20050003104).
References
1. Jan Sjövall. Lipids, 2004, 39, 703.
2. Enhsen A, Krame W, Wess G. Drug Discovery Today 1998, 3, 409.
3. Salunke DB, Hazra BG, Pore VS, Bhat MK, Nahar PB, Deshpande MV. J Med Chem 2004, 47, 1591.
4. Li CH, Peters AS, Meredith EL, Allman GW, Savage PB. J Am Chem Soc 1998, 120, 2961.
5. Merritt M, Lanier M, Deng G, Regen SL. J Am Chem Soc. 1998, 120, 8494.
6. Wess G, Kramer W, Enhsen A, Glombik H, Baringhaus KH, Bock K, et al. Tetrahedron Lett 1993,34,817
7. Virtanen E, Kolehmainen Erkki. Eur J Org Chem 2004, 3385.
8. Wallimann P, Marti T, Fürer A, Diederich F. Chem Rev 1997, 97,1567.
9. Zhang YH, Zhu XX. Macromol Chem Phys 1996, 197, 3473.
10. Zhu XX, Nichifor M. Acc Chem Res 2002, 35,539.
O
OCH 3
O
OCH 3

P-121
STUDY OF THE REACTION BETWEEN N- (O, O-DIISOPROPYL) PHOSPHORYL
AMINO ACIDS AND THE MIXED NUCLEOTIDES
Yanchun Guo 1 , Shuxia Cao 1 , Yali Xie 1 , Xianli Wu 1 , Xincheng Liao 1 , Yufen Zhao 1,2*
1. Key Laboratory of Chemical Biology and Organic Chemistry, Department of Chemistry, Zhengzhou University,
Zhengzhou, 450052, P.R.China
2. Key Laboratory for Bioorganic Phosphorus Chemistry of Ministry of Education, Department of Chemistry School of
Life Sciences and Engineering, Tsinghua University, Beijing 100084, P.R.China
Zhao’s group has found that N- (O,O-diisopropyl) phosphoryl amino acids (DIPP-aa) not only
are capable of self-assembly into oligopeptides but also can act as the phosphoryl donor to
phosphorylate nucleosides to nucleotides and oilgonucleotides 1,2 . Therefore, we selected four
oldest N- (O,O-diisopropyl) phosphoryl amino acids 3 and reacted with the mixed
nucleotides(A/C/G/U)in pyridine. In this system, dinucleoside monophosphate (XpY) and
dinucleoside diphosphate (XpYp-cyclo)(X,Y=A,C,G,U) were observed, then the possible target
products were validated by analyzing their cleavage pathways and their corresponding specific ions.
Backbone fragmentation was characterized by abundant c-ions as the major sequence-defining
fragment ion series. The results demonstrated that the four model reactions produced different kinds
of XpY and XpYp-cyclo at various range of contents, which was attributed to the different reaction
activity and selectivity. It might provide experimental proof for the assumption of Dipp-aa being
the smallest intermediate of co-origin of nucleic acids and proteins during origins of life.
Table1 ESI-MS n data for produces of DIPP-aa and four nucleosides m/z(IR/%)
Amino acid Compounds Precursor ion Fragment ion(relative intensity%)
Ala MS+ UpA 574.4(26)
439.2(12),421.3(100),379.1(16),337.0(7),307.1(11),
257.0(21), 195.1(11)
574.4/307.1 279.2(17),236.2(44),208.2(31),178.2(86),162.2(12),112.5(100)
UpC 550.3(10) 439.3(41),421.3(100),379.1(17),307.1(17),265.0(25),236.0(13)
550.3/307.1 279.2(17),236.2(44),208.2(31),178.2(86),162.2(12),112.6(100)
MS- UpU 549.3(17) 505.1(70),462.8(29),437.0(100),420.7(19),304.8(21),210.8(15)
549.3/304.8(12) 111.3(100)
Arg MS- CpGp-cyclo 648.8(7) 405.6(41),281.5(100)
648.8/405.6(10) 281.4(100)
GpGp-cyclo 688.7(100) 564.7(16),405.5(21),281.4(4)
688.7/405.5(70) 281.4(100)
Gly MS- UpC 548.0(18)
504.6(16),485.6(9),435.9(25),402.7(24),383.3(13),321.3(9),
303.6(19)
548.0/303.6 110.2(100)
References
[1] Zhou W H, Ju Y, Zhao Y F, et al. Origins Life Evol. Biosphere, 1996, 26:547.
[2] Zhao Y F, Hu J J, JU Y, Chin. Chem. Lett. 2000, 11(5):407.
[3] Woese C, [J].J Mol Evol 2:205-208.
102

P-127
ORGANOCATALYTIC FRIEDEL-CRAFTS ALKYLATIONS OF INDOLES WITH
DIALKYL
Ying-Cen Guo, Dong-Pin Li and Wen-Jing Xiao*
Key Laboratory of Pesticide and Chemical Biology, Ministry of Education College of Chemistry Central China
Normal University 152 Luoyu Road Wuhan Hubei 430079 China
wxiao@mail.ccnu.edu.cn
A series of new optically active α- indolylphosphonates have been synthesized with high
enantiometric purity via Friedel-Crafts alkylations using MacMillan second generation
organocatalyst with TFA as the catalytic system. The reaction gave promising results using
dichloromethane. The enantiomer excess (ee) of the product was up to 95%. This approach has
proved suitable for the synthesis of a wide range of α- indolylphosphonates.
R 1
N
R 2
+
O
P
R3 R
O
3O R 1 = 2-Me, 5-F, 6-Cl etc.
R 2 = Me, Allyl, Bn R 3 = Me, Et, iPr
O
N
103
N
H
O
Ph
CH 2Cl 2, -78 o C, 48hr
TFA
R 1
O
R P
3O R3O *
N
R 2
up to 95% ee
Reference
1. MacMillan, D. W. C.; Austin, J. F. J. Am. Chem. Soc. 2002, 124(7), 1172.
2. Sarkisyan, Z. M.; Makarenko, S.V.; Berestovitskaya, V. M.; Deiko L. I.; Berkova, G. A. Russ. J. of General Chem.
2003, 73(8), 1328.
O

P-129
SYNTHESIS OF L-PHENYLALANINE DIPEPTIDE MEDIATED BY
PHOSPHORUS OXYCHLORIDE AND SEPARATION BY RPLC
Ying-yan Yao,Kui-Lu*
(School of Chemistry and Chemical Engineering, Henan University of Technology, Zhengzhou 450052, China)
Phosphorus play vital roles in the chemical evolution of life. The recent years, self-assembling
into peptides for amino acids mediated by inorganic phosphorus has become a focus of science
research [1,2]
In this paper, the reactions of self-assembly into oligo-peptides for L-Phe mediated by inorganic
phosphorus were studied. To find the best experimental condition, the solvent, reaction time,
reaction temperature, the molar ratio of L-Phe and POCl3 were examined. These results were found:
the maximum length of peptides for L-Phe could reach hexapeptide, but time affected little the
reaction of self-assembly into oligo-peptides for L-Phe; The percent conversion of L-Phe in THF
was higher than that in 1,4-dioxane or acetonitrile, so THF was propitious to self-assembly into
peptides for L-Phe; Hoisting temperature could also speed the reaction and facilitate to produce
phosphoryl peptides, but too high(>50 ℃ ) would induce many side reactions; The reaction of
self-assembly into oligo-peptides would be speeded by increasing initial concentration of L-Phe. In
conclusion, the proper condition of direct synthesis was the molar ratio of L-Phe and POCl3 of 1 to
1, reaction temperature of 40 ℃ , reaction time of 2h and in THF as solvent.
The oligopeptides of L-Phenylalanine were purified with reverse-phase high performance liquid
chromatography (RP-HPLC) on C18 column, using methyl alcohol and water as mobile phase,
detect wavelength at 254nm,. The effect of the ratio of methyl alcohol and water in volume on the
separation was studied, and chromatographic conditions were optimized: With this optimized
condition (CH3OH: H2O, v/v =40:60), effluent of each peak was collected respectively to be
analyzed with ESI-MS/MS, this result indicated the self-assembly product could be separated with
HPLC well. That will provide a new method for Synthesis and Separation of oligo-peptide.
Figure HPLC analysis of mixture from L- phenylalanine mediated by POCl3
Acknowledgements: The authors would like to thank the financial supports from the Chinese
National Science Foundation (No.20272055, 20572016), Henan Province Science Foundation for
104

Prominent Youth (No.0312000900) and Office of Education of Henan Province (No.
2006KYCX017).
References:
1. Lu, K.; Liu, Y.; Zhou, N.; Chen, Y.; Feng, Y.-P. ; Guo, X.-F.; Chen, W.; Qu, L.-B.; Zhao, Y.-F. Acta Chim. Sinica
2002, 60 , 372 (in Chinese).
2. Zhou, N.; Lu, K.; Liu, Y.; Chen, Y.; Tang, G.; Cao, S.-X.; Qu, L.-B.; Zhao, Y.-F. Rapid Commun Mass Sp
2002,16 (8) , 790
105

P-130
SYNTHESIS OF SOME NEW 2-(BIS-Β-CHLOROETHYLAMIN)
7-METHOXYL-3-SUBSTITUTED PHENYL-4-METHYL-1, 3,
2-BENZOXAZAPHOSPHORIN 2-OXIDES
Yuan Jinwei 1 , Chen Xiaolan 1* , Qu Lingbo 1,2 , Yufen Zhao ,3
1
Department of Chemistry, Zhengzhou University, Zhengzhou, 450052, P. R. China
2
Anyang Normal College, Henan Province, Anyang, 455002, P. R. China
1, 3
The Key Laboratory for Bioorganic Phosphorus Chemistry, Department of Chemistry School Life Sciences and
Engineering, Tsinghua University, Beijing, 10084, P. R. China
Cyclophosphamine is an anticancer prodrug which has to be activated in the liver via conversion
by cytochrome P-450 to the cytotoxic phosphoramide mustard alkylating species. In the last four
decades, various cyclic and acyclic analogs of cyclophosphamide have been synthesized to
elucidate structure-activity relationships for phosphoramidate alkylating agents [1,2] . Although these
studies have not yet led to drugs superior to cyclophosphamide, it remains of great interest to
improve the physicochemical and biological properties of cyclophosphamide through structural
modification.
In this paper, we report the synthesis of some new 2-(bis-β-chloroethylamin) 7-methoxyl-3substituted
phenyl-4-methyl-1, 3, 2-benzoxazaphosphorin 2-oxides (Scheme 1) designed to increase
tumor selectivity and overcome tumor resistance. The structures of the products were defined by
ESI-MS, NMR and IR. Biological evaluation is in progress.
H 3CO
OH O
H 3CO
+
O
4a-g
NH 2
n-butanol
R H 3CO
P
N
O
N
R
106
OH
1a-g
R
N
NEt 3,Toluene
H 3CO
R=H, CH 3, C 2H 5, OCH 3, NO 2, F, Br, etc.
NaBH 4
methanol
H 3CO
OH
O
3a-g
2a-g
POCl 3
P
N
O
Cl
R
NEt 3 Toluene
Scheme 1
References
1. Zhuorong Li, Jiye Han, Yongying Jiang et al. Bioorganic & Medicinal Chemistry 2003, 11:4171-4178.
2. P V Govardhana, P Haranath, C Suresh Reddy et al. Indian Journal of Chemistry, 2005, 44B (7): 1432-1440.
Cl
Cl
HCl HN
Cl
Cl
Cl
O
P
Cl
N
Cl
Cl
4a-g
NEt3 Toluene
NH
R

P-132
THE REACTION OF PYRROLE-2,5-DIONES AND THEIR HALOGENATED
DERIVATIVES WITH TRIVALENT PHOSPHORUS COMPOUNDS
Yuen-Ki Cheong, Philip Duncanson and D. Vaughan Griffiths
School of Biological and Chemical Science, Queen Mary, University of London, Mile End Road, London, E1 4NS, UK
As part of our studies into the reactions of organic carbonyl compounds with nucleophilic
trivalent phosphorus compounds, we have been investigating the reactions of a number of
substituted pyrrole-2,5-diones and their halogenated derivatives with trialkyl phosphites, dialkyl
phosphonites and alkyl phosphinites. These studies have already resulted in the formation of novel
products by some interesting reaction pathways.
O
O
O
(EtO) 3P
1
O
NH
107
HN
O
O
P(OEt) 2
Thus, for example, the reaction of triethyl phosphite with pyrrole-2,5-dione gave not only the
anticipated ylide 1 but also the phosphonate 2, whose structure was confirmed by X-ray
crystallography. The incorporation of halogen substituents at C-3 and/or C-4 in the
pyrrole-2,5-diones has proved to be a convenient route for introducing additional phosphonate
groups into the final ylide. Thus, for example, the reaction of
3-bromo-4-methyl-1-phenyl-1H-pyrrole-2,5-dione 3 with Ph2(MeO)P proceeded cleanly to give the
crystalline ylide 4, whose structure was also confirmed by X-ray crystallography.
Cl
Cl
O
O
N
Br
Me
5
O
O
NPh
MeO
P
O
(MeO) 2P
(MeO) 2P
O
OMe
MeO
OMe
Ph2P O
(Ph) 2P
Me
O
O
N
NPh
3 4
O
O
NEt
O
2
O
(HO) 2P
O
(HO) 2P
(HO) 2P
O
6 7
Extending this approach to 3,4-dihalogenated precursors led to the formation of ylidic
bisphosphonates. Thus, for example, the N-allyl substituted system 5 reacts with trimethyl
phosphite to give the ylide 6, which has been converted into the trisphosphonate 7. Polymerisation
of this latter compound potentially offers a novel route to highly functionalised polymers.
O
O
N

P-134
SYNTHESIS OF DIPHENYL Α-(O-PHENYL
BIS(2-CHLOROETHYL)AMIDOPHOSPHORYLAMINO)PHOSPHONATES
Zhanwei Cui, Zhiwei Miao,∗ Jianfeng Zhang and Ruyu Chen
State Key Laboratory of Elemento-Organic Chemistry, Research Institute of Elemento-Organic Chemistry, Nankai
University, Tianjin 300071, People’s Republic of China. *Email: miaozhiwei@nankai.edu.cn
The phosphoryl group is of fundamental significance in many of the most important molecules
that control molecular replication, cell biochemistry and metabolic processes in all living species. 1-4
On the other hand, α-Amino phosphonates constitute an important class of biologically active
compounds, and their synthesis has been a focus of considerable attention in synthetic organic
chemistry as well as in medicinal chemistry.
Nitrogen mustards (NMs) are useful chemotherapeutic agents in the treatment of lymphoma,
leukemia, multiple myeloma and ovarian carcinoma. 5 The antitumor activity of NMs has been
attributed to their ability to cross-link the twin strands of DNA. Phosphoramide mustard is also an
alklating agent that cross-links interstrand DNA, such as cyclophosphamide (CP),ifosfamide (IFA)
and trofosfamide. 6-9 Cyclophosphamide is a widely used anticancer alklating agent that requires
activation in vivo. It can liberate cytotoxic phosphoramide mustard and acrolein by β-elimination.
However, acrolein, a byproduct of β-elimination, can cause hemorrhagic cystitis, a side effect
observed during CP therapy. To overcome the shortcoming of CP, many different kinds of
compounds containing phosphamide mustard have been designed and synthesized. 10-12 On that basis,
we designed and synthesized the title compound to find novel anticancer prodrug.
We report here a facile synthetic method for the preparation of Diphenyl α-(O-phenyl
bis(2-chloroethyl)amidophosphorylamino)phosphonates (4). It consists of the reaction of O-phenyl
bis(2-chloroethyl)amidophosphoroamidoate (1) with a substituted benzaldehyde or ketones (2) and
triphenylphosphite (3) in the presence of acetyl chloride as catalysis. 13 The present method affords
higher yields in the condensation reaction and high purify. (Scheme 1)
Reference
[1] Zhou, J.; Chen, R. Y. Phosphorus, Sulfur, Silicon 1996, 118, 247.
[2] Bergman, J.; Van der Plas, H. C.; Simonyi, M. Heterocycles in Bioorganic Chemistry; RSC: Cambridge, 1991.
[3] Meier, C. Angew. Chem., Int. Ed. Engl., 1996, 35, 70.
[4] Yuan, C.; Qi, Y. Synthesis 1986, 821.
[5] Balcome, S.; Park, S.; Danae R.; Dorr, R.; Hafner, L.; Phillips, L.; Tretyakova, N. Chem. Res. Toxicol. 2004, 17,
950-962.
108

[6] Sladek, N. E. Pharmacol. Ther. 1988, 37, 301-305.
[7] Friedman, O. M.; Myles, A.; Colvin, M. Adv. Cancer Chemother. 1979, 1, 143-204.
[8] Ludeman, S. M. Curr. Pharm. Des. 1999, 5, 627-643.
[9] Colvin, O. M. Curr. Pharm. Des. 1999, 5, 555-560.
[10] Borch, R. F.; Liu, J. W.; Schmidt, J. P.; Marakovits, J. T.; Joswig, C.; Gipp, J. J.; Mulcahy, R. T. J. Med. Chem.
2000, 43, 2258-2265.
[11] Hu, L. Q.; Yu, C. Z.; Jiang, Y. Y.; Han, J. Y.; Li, Z. R.; Browne, P.; Race, P. R.; Knox, R, J.; Searle, P. F.; Hyde, E.
I. J. Med. Chem. 2003, 46, 4818-4821.
[12] Jain, M.; Kwon, C. H. J. Med. Chem. 2003, 46, 5428-5436.
[13] Yuan, C.; Qi, Y. Synthesis .1988, 472.
109

P-138
MODIFIED ALKALOIDS AS ORGANOCATALYSTS FOR THE ASYMMETRIC
SYNTHESIS OF ORGANOPHOSPHORUS COMPOUNDS
A.O. Kolodiazhnaya, V.P.Kukhar, O.I. Kolodiazhnyi
Institute of Bioorganic Chemistry and Petrochemistry, National Academy of Sciences of Ukraine,
Murmanskaya str. 1, Kiev, 02094 Ukraine
Organocatalysis is the acceleration of chemical reactions with a substoichiometric amount of an
organic compound which does not contain a metal atom.
As an important subset of the larger field of organocatalysts, interest in amino acid and
peptide-based catalysts has increased over the past decade. Important progress has been made in the
development of asymmetric reactions with amino acid (proline) and peptide-based catalysts.
Cinchona alkaloids 1 (cinchonine, cinchonidine, quinine, etc.) are accessible and effective reagents
for the asymmetric synthesis and are widely in organic chemistry [1].
In this work we have studied the modified alkaloids 1-3 as organocatalysts for phospho-aldol
reaction. We have found that the bifunctional cinchona derivatives 1-3 act as asymmetric
catalysts in the phosphor-aldol reaction. By means of these catalysts both optical antipods of
hydroxyalkylphosphonic acids have been obtained. Good enantiomeric excesses were achieved with
activated aromatic aldehydes.
Stereoselectivity of catalysts in case of a single asymmetric induction (R=Et) was good and high
in case of a double and triple asymmetric induction. Products 4,5 were purified by crystallization
and were isolated as chemically and optically pure compounds. The optical purity of these
compounds was studied by means of NMR chiral solvating reagents [1]. The absolute configuration
of the new stereogenic center in 4 and 5 was also assigned by analogy with other
hydroxyphosphonates using the method of chemical correlation.
The most effective were catalysts obtained on the base of quinine and cinchonidine (R=H,
R’=PhCH2)
N
OR'
OR
N
H
N
OR'
OR
1 2
R'
(RO) 2 P(O) OH
H
110
N
H
N
R=H, OMe;
R' = Me3Si, Ph2P, Me, PhCH2 R'CH=O
R'CH=O
(RO) 2P(O)H 1 DBU or 2
4 5
R'
3
(RO) 2 P(O) H
OH
References
1 O.I. Kolodiazhnyi Tetrahedron: Asymmetry 2005, 16, 3295.
2 A.O. Kolodiazhnaya, V.P.Kukhar, O.I. Kolodiazhnyi J.Gen.Chem.Russ, 2006, 76, 1342.
N

P-144
REACTIONS OF AMINOACETYLENEPHOSPHONATES WITH
N-NUCLEOPHILIC REAGENTS
Anastasia V. Aleksandrova, Alla V. Dogadina, and Boris I. Ionin
St. Petersburg State Technological Institute (Technical University), Moskovskii pr., 26, St. Petersburg, 190013, Russia,
E-mail: ana_alexandrova@mail.ru
Aminoacetylenephosphonates (phosphorylated ynamines) thanks to their structure are able to add
neutral N-ucleophilic reagents across the triple carbon-carbon bond and these reactions are carried
out strongly regioselectively with the formation of new interesting compounds possessing potential
biological activity. We performed a complex investigation of the reactions of “typical”
aminoacetylenephosphonates (i.e. obtained by the described method from
chloroacetylenephosphonates and high-basic secondary amines [1]) with primary and secondary
amines differ by their basic properties and steric characteristics. Thus, we found that at the reactions
of phosphorylated ynamines with both primary and secondary amines, the basic property of the
involved amine is significant for the chemoselective formation of the corresponding phosphonate
structure. Reactions of aminoethynephosphonates with the primary amines with pKa 1-5 (mainly,
aromatic amines) and secondary amines of the same basicity lead to formation of unsymmetrical
phosphorylated acetamidines (Scheme 1) and 2,2-diaminoethenphosphonates (Scheme 2)
respectively [2,3] in the absence of a catalysts.
1 h, Δ
(RO) 2PC CNR'2 H2NAr (RO) 2PCH2C CCl4 O O
NAr
Scheme 1
NR'2 R=Me, Et; NR'2= NEt2, N[(CH2) 2] 2, N(CH2) 5; Ar= Ph, 4-MePh, 4-MeOPh, 4-ClPh, 2-ClPh, etc.
(RO)
2-3 h, Δ
2(O)P NR'2 (RO) 2PC CNR'2 HNR''2 CCl4 O
H NR''2 R=Me, Et; NR'2=NEt2, N(CH2) 5; HNR''2=HN(Me)Ph, HN(Ph)CH2Ph, H N
111
Scheme 2
Further, we found that reactions of aminoacetylenephosphonates with low-basic and high-basic
primary and secondary amines proceed more difficultly under rigid conditions or in the presence of
acid catalysts (we used boron trifluoride etherate) with the formation of corresponding
phosphonates or amidophosphates (with high-basic primary amines). Amines with bulky fragments
such as t-butyl amine react with investigated ynamines by a specific way: the main product of this
reaction is phosphorylated diaminoethene [4]. Thus, we showed that composition of the products of
reactions of phosphorylated ynamines with primary and secondary amines depends on both basic
property of the amine and its steric structure.
References
[1] Garibina, V.A., Dogadina, A.V., Ionin, B.I., and Petrov, A.A., Zh. Obshch. Khim., 1979, vol. 49, no. 10, p.
2385-2386
[2] Panarina, A.E., Aleksandrova, A.V., Dogadina, A.V., and Ionin, B.I., Rus. J. Gen. Chem., 2005, vol. 75, no. 1, p. 3-8
[3] Aleksandrova, A.V., Dogadina, A.V., and Ionin, B.I., Rus. J. Gen. Chem., 2005, vol. 75, no. 10, p. 1664-1666
[4] Panarina, A.E., Aleksandrova, A.V., Dogadina, A.V., and Ionin, B.I., Rus. J. Gen. Chem., 2004, vol. 74, no. 9, p.
1459-1460

P-154
TEMPLATE-DIRECTED SYNTHESIS OF PHOSPHOROUS CONTAINING
MACROCYCLES:STRUCTURE/REACTIVITY-RELATIONSHIPS
S. Bozkurt, S. Ekici, D. Jaspers, M. Nieger, E. Niecke*
Anorganisch-Chemisches Institut der Universität Bonn, Germany
An efficient synthetic strategy towards macrocycles is reported, which gives access to ligands with
discriminative functionality and redox activity The strategy is based on a coupling reaction between
two alkali metal-fixed, carbanionic centers I (template) and two specifically connected electrophilic
centers II (substrate). A macrocyclic ate-complex III is formed by a two fold P-C coupling reaction.
Subsequently, III can be converted to the neutral ring system IV by electrophiles (scheme). Insights
into structure/reactivity relationships for transition metal complexes V from these macrocycles are
reported.
References:
[1] S. Ekici, D. Gudat, M. Nieger, L. Nyulászi, E. Niecke, Angew. Chem. Int. Ed. 2002, 41, 3367.
[2] S. Ekici, M. Nieger, R. Glaum, E. Niecke, Angew. Chem. Int. Ed. 2003, 42, 435.
[3] S. Bozkurt, Thesis, University of Bonn 2004.
[4] S. Ekici, Thesis, University of Bonn 2005.
[5] S. Ekici, D. Jaspers, E. Ertürk, M. Nieger, A. Berkessel, E. Niecke, in preparation.
[6] S. Ekici, D. Jaspers, M. Nieger, M. Kogei, C. Schalley, E. Niecke, in preparation.
112

P-159
SYNTHESIS AND STRUCTURE OF THIOPHENE, SELENOPHENE, AND RELATED
COMPOUNDS CARRYING FOUR PHOSPHORYL GROUPS
Shigeru Sasaki, Kazutaka Adachi, Masaaki Yoshifuji, and Noboru Morita
Department of Chemistry, Graduate School of Science, Tohoku University
Aoba, Sendai 980-8578, Japan
E-mail: sasaki@mail.tains.tohoku.ac.jp
Construction of the cyclic compounds fully substituted by phosphorus functional groups has
attracted considerable attention, since intramolecular interactions between the phosphorus
functional groups with the ring systems as well as with the neighboring phosphorus functional
groups and construction of various molecular assembly based on coordination or hydrogen bond
formation are expected. Such compounds can be potential candidates for various novel materials
especially for biomedical materials taking various functions of phosphoric acid and its derivatives
in biological systems into consideration. Recently, we reported synthesis of the
( η 4 -tetraphosphorylcyclobutadiene)cobalt complexes from the diphosphorylacetylenes and
construction of the one-dimensional coordination polymer.1 Herein, we report formation of
dihydrotetraphosphorylthiophene 2 from diphosphorylacetylene 1, oxidation of 2 to
tetraphosphorylthiophene 3, and analogous synthesis of the corresponding selenium compounds 4
and 5.
Reaction of less than a half equivalent of sodium hydrosulfide with 1 in ether gave
dihydrothiophene 2. Although attempted aromatization of 2 with o- or p-chloranil, or DDQ resulted
in recovery of 2, oxidation of 2 with mCPBA afforded the corresponding sulfoxide, and dehydration
of the sulfoxide gave thiophene 3. Employment of sodium hydroselenide in place of sodium
hydrosulfide gave 4, and oxidation of 4 with mCPBA afforded 5. Esters 2 and 3 can be converted to
the corresponding phosphonic acids. Detailed structures and reactivities of these tetraphosphoryl
heterocycles will be discussed.
References
1) Sasaki, S.; Tanabe, Y.; Yoshifuji, M. Chem. Commun. 2002, 1876; Sasaki, S.; Kato, K.; Tanabe, Y.; Yoshifuji, M.
Chem. Lett. 2004, 33, 1004.
113

P-164
SYNTHESIS OF NEW β-AMINO-DERIVATIVES OF ALKENYLPHOSPHONATES
R.A.Cherkasov, N.G.Khusainova, O.A.Mostovaya, E.A.Berdnikov, S.M.Rybakov
Kazan State University, Kremlevskaya str.18, Kazan, 420012, Russia
e-mail: narkis.khusainova@ksu.ru; rafael.cherkasov@ksu.ru
The development of synthesis methods of the polyfunctionalized compounds is very important
because they are used as extracting agents for noble metals, biological active substances. High
reactivity of phosphorylated allenes enables to use them in the synthesis of new β-aminoderivatives
of alkenylphosphonates. We have studied the interaction of 3,3-dimethylallenylphosphonates with
1,2-diaminoethan.
Me
-
Me
(EtO) 2P(O)CH C C
I
Me
+
H 2NCH 2CH 2NH 2
(EtO) 2P(O)CH
114
C
H 2N
II A
+
Me
Me
Me
+
NH 2
C
CHP(O)(OEt) 2
Me
Me
(EtO) 2P(O)CH2 C
(EtO) 2P(O)CH C
Me
Me
N
HN
N
NH
Me
Me
C CH
C CHP(O)(OEt)
2P(O)(OEt) 2
2
Me
Me
IV
III
The X-ray data is showed that the reaction of diethyl-3,3-dimethylallenylphosphonate I with
diamine II proves the formation of 2:1 addition product with enamino-structure III. By 1 H and 31 P
NMR spectroscopy it was determined that enamine III in solvents proves the formation of
tautomeric enamines and imines IV.
We have investigated reactions of 3,3-dimethylallenylphosphonates with 2-aminobenzo-thiazole
V. By X-ray diffraction analysis it was determined that the reaction of diethyl
3,3-dimethylallenyl-phosphonate I with thiazole V involves the endocyclic N atom of compound V
and the 1,2-double bond of phosphonate I.
-

P-165
DITHIOPHOSP ORYLATION OF CYCLIC MONOTERPENES
Il’yas S. Nizamov 1, 2 , Artiem V. Sofronov 1 , Rafael A. Cherkasov 1 , Liliya E. Nikitina 3
1
Kazan State University, Kremlievskaya Str., 18, Kazan, 420008, Russia
e-mail: Ilyas.Nizamov@ksu.ru lyas.Nizamov@ksu.ru
2
A.E. Arbuzov Institute of Organic and Physical Chemistry, Arbuzov Str., 8, Kazan, 420088, Russia,
3 Kazan State Medical University, Butlerov Str., 49, Kazan, 420012, Russia
There is a considerable interest in derivatives of cyclic monoterpene series compounds containing
functional groups due to their possible use as biological activity substances. The importance of
these compounds is also related to their skeleton structure transformations. O,O-Dialkyl
dithiophosphoric acids have been reported to react with terpenes such as -pinene and dipentene at
100-200 o C with the formation of additives for lubricants [1, 2]. We assumed that the initial
products obtained in these patent works undergo decompositions under severe conditions used. We
have carried out the reactions of dithiophosphoric acids with such terpenes as racemic camphene,
(+)-limonene, (1S)-(-)- -pinene and 3-carene under milder conditions and search appropriate
catalysts of addition reactions. We have found that these reactions occur at room temperature for
1-3 h in the presence of catalytic amounts of anhydrous ZnCl2 to yield adducts formed in
accordance with Markovnikow’s rule. In the case of camphene the adduct formation is accompanied
by skeleton transformation into norbornane structure.
S
(RO)
2
PSH +
R = Et, Pr-i
ZnCl 2
(1 %)
20 o C, 1-2 h
115
S
S-P(OR) 2
The reactions O,O-dialkyl dithiophosphoric acids with (+)-limonene proceed with the participation
of the exocyclic C=C bond.
S
(RO)
2
PSH +
R = Et, Pr-i
ZnCl 2
(1 %)
20 o C, 2-3 h
S
S-P(OR) 2
The reactions studied are facilitated by Lewis acid cataysts (NiCl2, CuCl, CuCl2, FeCl3, BF3 . Et2O,
AlCl3). The reactions of O,O-dialkyl dithiophosphoric acids with (1S)-(-)- -pinene can also be
performed non-catalytically.
References:
[1] Pat. US 2611728 (1952). / Barlett J.H., Rudel H.W., Cyphers E.B., Chem. Abstr. 1953, 43, 930a.
[2] Pat. US 2665295 (1954). / AUGUSTINE F.B., Chem. Abstr. 1954, 48, 12807F.

P-171
GREEN SYNTHESIS OF PHOSPHORAMIDES BY TRIMETAPHOSPHATE(P3m)
NI, F.; Fu, C.; Sun, S. T.; Zhao, Y. F
Key Lab of Chemical Biology of Fujian Province, Department of Chemistry, Xiamen University
Xiamen, 361005, China
A green synthesis method with organic reagent free and efficient purificaiton procedure was
developed to synthesize the phosphoramides, such as N-phosphoryl amino acids and N-phosphoryl
dipeptides. This synthesis used trimetaphosphate (P3m) , a cheap and easily available phosphate, as
the phosphorylated reagent and came out with target compounds and inorganic phosphates, later of
which could be recycled to produce P3m.
O O
3Na
P
O O
O O + H2N R
P P
O
O O
pH=10.5-11.5
H 2O
NH2-R= α Amino acids,
β Amino acids,
γ Amino acids,
dipeptide
O
O
P P
O P
O
O
O O
O
O
O
NH CH C
H
O
O
P P
O P
O
O
O O
O
O
NH R
116
Scheme
O -
CaO
fast
NaOH
O
O
O
O
O
O
O
P
O
O
P
O
P
NH
CH2
OH -
O
2Na
NH R
O
O
P
+ P2
3Na
NH R
+ P2
+ Pi

P-175
PHOSPHINOGLYCINES AND PHOSPHINOGLYCOLATES
J. Heinicke, a J. Lach, a N. Peulecke, a P. G. Jones, b I. Dix c
Universität Greifswald a (Germany), Technische Universität Braunschweig b (Germany),
University Göttingen c (Germany)
A one-pot three component synthesis of novel α-phosphino glycines and α-phosphino glycolates
is presented.
(HO)2CHCOOH
1/2 cHex2P +
Et2NH2 + cHex2PH + Et2NH
+
5
CH
OH
COO -
+ Ph2PH + AlkNH2
2
Alk
H 2N
+ *
O
HO *
O
4
117
PPh 2
O -
H 2O
PPh2
O -
1
AlkNH3 +
+ Et 2S BH 3
S (MeOH)
H2N
Alk BH3
+ *
O
H2N
PPh2
O -
Alk S
Chiral amines induce high diastereoselectivity and allow, in suitable cases, one-step syntheses of
chiral phosphine ligands. Crystal structure analysis gives evidence on the preferred configuration.
Properties of the novel compounds and first examples of use in catalysis are presented.
Reference
[1] J. Heinicke, N. Peulecke, DE 10 2004 029 697.9 (AT: 15. 06. 2004), DE 10 2004 029 698.7 (AT: 15.
Juni 2004), PCT/DE2005/000969 (AT: 26. 05. 2005), PCT/DE2005/000970 (AT: 26. 05. 2005).
+ *
O
2
PPh2
O -
3

P-178
STEREOSPECIFIC PREPARATION OF P-CHIROGENIC PHOSPHIDE BORANES FROM
THE CORRESPONDING CHLOROPHOSPHINES
H. Lauréano, a G. Morata, a M.L. Auclair, a J.C. Henry, b P. Richard, a C. Darcel a and S. Jugé a*
[a] Inst. Chim. Mol. de l'Université de Bourgogne,UMR CNRS 5620, 9 av. A. Savary,
21078 Dijon, France; Fax 33 3 80 39 60 98; e-mail: Sylvain.Juge@u-bourgogne.fr
[b] SYNTHELOR SAS- 102 impasse H. Becquerel, Dynapôle de Ludres-Fléville 54510 Ludres, France
In the recent past, significant advances have been made for the asymmetric synthesis of
P-chirogenic phosphorus ligands, owing to the use of borane protecting group. The synthesis of
such ligands is usually performed with phosphorus-carbon bonds formation using P-chirogenic
phosphinous derivatives 1 or phosphide boranes, 2,3 as electrophilic or nucleophilic building blocks,
respectively. Until now, the P-chirogenic phosphides borane are usually prepared by deprotonation
of the corresponding secondary phosphine boranes in presence of sparteïne, 2 or by metal reduction
of a phosphinous borane precursors. However, this method gives high stereoselectivities only when
the phosphine boranes bears a sterically hindered substituents as adamantane or t-butyl.
Cl
BH 3
P
Ph
R 1
t-BuLi
-78°C
Li
1 2
BH 3
P
Ph
We report herein a new efficient route to the P-chirogenic phosphide boranes 2, by
stereoselective metal halide exchange of the corresponding chlorophosphine boranes1 with the
t-butyllithium. The phosphide boranes 2 were then used for the preparation of various secondary 3
or tertiary phosphine boranes 4 in high enantiomeric excesses, by protonation with AcOH or
trapping with an alkyl halide, respectively.
Reference
1) Bauduin, C.; Moulin, D.; Kaloun, E.B.; Darcel, C.; Jugé, S., J. Org. Chem., 2003, 68, 4293-4301.
2) Wolfe, B.; Livinghouse, T. J. Am. Chem. Soc. 1998, 120, 5116-5117.
3) Miura, T.; Yamada, H.; Kikuchi, S.-I; Imamoto, T. J. Org. Chem. 2000, 65, 1877-1880.
R 1
AcOH
118
R 2 Br
H
R 2
BH 3
P
3
BH 3
P
4
Ph
Ph
R 1
R 1
yield 60-75 %
88-94% e.e.
yields 21-75 %
87-99% e.e.

P-179
RECENT PROGRESSES ON P-CHIROGENIC PHOSPHINE SYNTHESIS
M. L. Auclair, a G. Morata, a M. Gomès, a S. Loutsenko, a J. C. Henry, a P. Richard, a
C. Darcel a and S. Jugé a *
[a] Institut de Chimie Moléculaire de l'Université de Bourgogne,UMR CNRS 5620, 9 av. A. Savary, 21078 Dijon,
France; Fax 33 3 80 39 60 98; e-mail: Sylvain.Juge@u-bourgogne.fr
[d] SYNTHELOR SAS- 102 impasse H. Becquerel, Dynapôle de Ludres-Fléville 54510 Ludres, France
Organophosphorus ligands bearing chirality on the phosphorus atom are not been the most used
ligands in asymmetric catalysis until now, mainly due to the difficulty of their stereoselective
preparation. Nevertheless, as their asymmetric synthesis has made in the recent past, important
progresses due to the use of borane complexes, these ligands receive again a particular interest in
coordination chemistry and catalysis, for the possibility to increase the steric and electronic
dissymmetry of the metal center.
R
Ph
1
o-Tol
Ph
P
Br
R
Ph
1
P
P
NH 2( OH)
Fe
Ph
o-An
P
Ph
Cl
P
BH 3
P
R
Ph
1
NHPh
119
P Ph
Ph
Fe
R
Ph
1
P
R
Ph
1
P
O
P
O
R2
R3 R
Ph P P
1 Ph
R1 We report herein the synthesis of new P-chirogenic ligands: bulky monophosphinites,
ferrocenylphosphines, o-hydroxy-, β-aminophosphines, phosphine-phosphinites, pincer ligands,
indenylphosphines, and their uses in coordination chemistry or asymmetric catalysis.
References
1) C. Bauduin, D. Moulin, E.B. Kaloun, C. Darcel, S. Jugé J. Org. Chem. 2003, 11, 4293–4301.
2) J.M. Camus, J. Andrieu, P. Richard, R. Poli, C. Darcel, S. Jugé Tetrahedron : Asymmetry 2004, 15, 2061-2065.
O
O

P-186
SYNTHESIS OF HEXAISOPROPYLTRIAMIDEPHOSPHITE: MYTH OR REALITY?
Anatoliy P. Marchenko, Georgyi N. Koidan, Yurii M. Pustovit , Mark I. Povolotskii, Aleksandr N. Chernega,
Aleksandr M.Pinchuk,
Institute of Organic Chemistry National Academy of Sciences of Ukraine,
Murmanska Str.5, Kyiv, 02094 Ukraine
It has already been informed that triamide (i-Pr2N)3P 1 was prepared by the reaction of
phosphorus trichloride with di(isopropyl)amine 2. [1,2] At the same time our investigations and
results of work [3] testify that this reaction stops affording (i-Pr2N)2PCl 3 due to steric hindrance.
Moreover, it was found that di(isopropyl)amine 2 easily reacts with less sterically hindered and
more electrophilic phosphenium cation (i-Pr2N)2P + CF3SO3 - 4. Nevertheless, the reaction doesn’t
lead to the triamide 3, but it gives the diphosphine i-PrN=C[CH2P(iPr2N)2]2 5. The diphosphine 5
formation most probably takes place via the reaction of the phosphenium cation 4 with ketimine
i-PrN=CMe2 forming in the course of the reaction that was confirmed experimentally. [4]
iPrN=CMe 2 + (i-Pr2N) 2P + CF3SO - (i-Pr 3 2N) 2P-CH2CCH3 =NPr-i
-BH +
(i-Pr 2 N) 2 P + CF 3 SO 3 -
-BH +
4
B:
iPrN=C(CH 2 P(NPr-i 2 ) 2 ) 2
Unlike the phosphenium cation 4, chlorophosphite 3 reacts with an excess of ketimine giving
dihydroazaphosphinine.
N P
NHPr-i
i-Pr
iPrN=CMe 2 + (i-Pr 2 N) 2 PCl
3
At the same time the reaction of the phosphenium cation 4 with less sterically hindered
methylisopropylamine HNMe(Pr-i) leads to triamide (i-Pr2N)2 PN(Me)Pr-i.
The synthesis of triamide 1 using the above-mentioned methods most probably could not be
accomplished. An approach to triamide 1 has to be found yet.
References
1. Michaelis A., Lieb. Ann., 326, 129 1903.
2. Nifantyev E.E., Suvorkin S.V., Rasadkina E.N. et al Zhur.Obshch.Khimii 2002, 72, 8, P. 1263-1266
3. Foss V.L., Lukashev N.V., Lutsenko I.F. Zhur.Obshch.Khimii 1979, 50, 6, P.1236-1245.
4. Hund H, Hund R-D., Has S., et al Phosphorus, Sulfur and Silicon, 1996, Vol.111, P.193
120
5
6
B:

P-187
A CONVENIENT METHOD FOR THE SYNTHESIS OF
CYCLOPHOSPHAMIDE ANALOGUES
Zhang Liuji 1 , Qu Lingbo 1,2 , Zhang Baojun, Zhao Yufen 1
1 Department of Chemistry, Zhengzhou University, Zhengzhou, 450052, P. R. China
2 Anyang Normal College, Henan Province, Anyang, 455002, P. R. China
E-mail: qulingbo@zzu.edu.cn
Cyclophosphamide is an anticancer prodrug, which has better effection on most malignant tumor
cells, but it has also toxicity and side-effect on normal human cells. In the last four decades, in
efforts to obtain potential anticancer prodrugs and decrease the side-effect of cyclophosphamide,
modifications of cyclophosphamide led to the design and synthesis of many cyclic and acyclic
phosphoramidate agents. However, these extensive structure-activity relationship studies failed to
produce better drugs than cyclophosphamide.
In this paper, we report a convenient method for the synthesis of some new cyclophosphamide
analogues (Scheme 1). These structures might be used as potential cyclophosphamide analogues
designed to increase tumor selectivity, overcome tumor resistance, etc. The structures of the
products were defined by ESI-MS, NMR and IR. Biological evaluation is in progress.
H 3CO
OH
O
CH 3
H
NaBH 3CO
4
CH3OH H 3CO
THF
NEt3 Cl
OH
CH 3
O
P
Cl
O
OH
Cl2P(O)N(CH2CH2Cl) 2 H3CO H
N R
P
O
CH 3
O
N
H
R=H, CH 3, OCH 3, F, Cl, Br
Scheme 1
121
Et 3N, THF
References
1. Zhuorong Li, Jiye Han, Yongying Jiang et al. Bioorganic & Medicinal Chemistry 2003, 11:4171-4178.
2. Y B Kiran, M Kasthuraiah, C Nagaraju et al. Indian Journal of Chemistry, 2005, 44B (11): 2171-2177.
Project was supported by NNSFC (No. 0472076) and HNSTF (No. 0512001400)
R
O
CH 3
O
P N(CH2CH2Cl) 2
O

P-188
CONVENIENT SYNTHESIS OF α-HYDROXYPHOSPHINATE
Tao Ji, Guo Tang , Hua Fang, Yufen Zhao*
Department of Chemistry and The Key Laboratory for Chemical Biology of Fujian Province, College of
Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, P. R. China.
Abstract: α-Hydroxyphosphinate are compounds with wide ranging biological activities and useful
synthetic intermediates for a variety of natural and complex molecules. The Pudovik reaction is the
most versatile pathway to the above compounds. The reaction is very sluggish without Me3SiCl. It
was found that this reaction is markedly accelerated in presence of Me3SiCl when basic catalysts
are added. O-alkyl phenylphosphonite was formed by the reaction of O-alkyl phenylphosphonite 1
with aromatic aldehydes in presence of Me3SiCl and Et3N.
O
Cl
Et O
3N
P + R OH PH + CHO P
Cl
Me3SiCl OR
OR
R=
1 2 3
CH3 , CH2CH3 , CH(CH3) 2 , C(CH3) 3 ,
R Reaction
conditions
CH3CH2-
122
Reaction Time(h) Yield(%)
Me3SiCl 6 70
Me3SiCl and Et3N 1 81
Me3SiCl 4 75
Me3SiCl and Et3N 0.5 88
References
[1] Mastalerz, P. In Handbook of Orgnophorus Chemistry; Engel, R. (Ed.) New York, 1992; pp.299-305
[2] Texier-boullet, F; Foucauld. A, Synthesis 1982, 165;
[3] Jue-xiao Cai; Zhenghong Zhou, Heteroatom Chemistry, 2003, 14, 312-315
OH

P-190
SYNTHESIS OF N-(DIISOPROPYLOXYPHOSPHORYL)DIPEPTIDES
IN A ONE-POT METHOD
Kan Lin, Xiantong Huang, Guo Tang, Yufen Zhao
The Key Laboratory for Chemical Biology of Fujian Province,Department of Chemistry and College of Chemistry and
Chemical Engineering, Xiamen University, Xiamen 361005, P. R. China.
Derivatives of N-phosphopeptides are of pharmaceutical and biologically active interst. Several
methods for their synthesis are known. Because an efficient method to prepare highly pure and large
quantities of N-phosphoamino acids has been developed in our laboratory, we can use
N-(dialkoxyphosphoryl)amino acids as stock material. In this paper, coupling of
N-(diisopropyloxyphosphoryl)amino acid and amino acid methyl esters, by the adduct of
triphenylphosphine, hexachloroethane and triethylamine in one-pot, produced N-DIPP-dipeptide
methyl esters which then were hydrolyzed to get corresponding N-DIPP-dipeptide. Target products
were determined by NMR, ESI, and optical rotatory power. We hope that this convenient and
efficient approach could be generally used for synthesis of polypeptides.
O
O
P
O
H
N H C
R1 COOH
2
+ Ph3P
O O
P
H
N
O
H C
R1 O
C O
H
NH C
R2 + C2Cl6 COOMe
5
HCl H2N i Et3N+H2O
ii H +
H
C
R 2
123
COOMe
Et3N , CH2Cl2
O
O
P
O
H
N H C
R 1
O
C
O
O
P
H
N
O
H C
R 1
O
C
6
O
5
O
H
NH C
R 2
COOH
H
NH C
R2 O
COOMe + Ph3P Table 1. The yields of the N-DIPP-peptides
Compound DIPP-Ala-Ala DIPP-Ala-Phe DIPP-Phe-Phe DIPP-Phe-Ala DIPP-Phe-Ile
Yields(%) 71 79 78 87 85
References
[1] Shu-Zhi Dong et al. Synthetic communications. 2001, 13, 2067.
[2] Gai-Jiao Ji et al. Synthesis. 1988, 6, 444.

P-191
ORGANICPHOSPHORUS COMPOUNDS AS SMALL MOLECULAR CATALYSTS IN
THE DIRECT ASYMMETRIC ALDOL REACTION
Qin Tao, Guo Tang*, Yu-Fen Zhao
Department of Chemistry and The Key Laboratory for Chemical Biology of Fujian Province, College of Chemistry and
Chemical Engineering, Xiamen University, Xiamen 361005, P. R. China.
Chiral organophosphorus compounds have been synthesized and applied in the direct asymmetric
aldol reaction as chiral catalysts. High enantioselectivities were achieved for a series of ketones and
substituded benzaldehydes.
In this article we synthesize chiral organicphosphorus [1], [2] 1 and 2( Fig. 1), then apply them as
chiral catalysts in the direct asymmetric aldol reaction and obtain good enantioselectivities (Scheme
1). Other nucleophilic reactions such as Michael addition are under researching.
R
R= NO2 Cl
CN
O
+
O
N
H
O
P O
O N
H
1 2
O
( )
Fig. 1
124
1or2
O
P
O
O
acetone/DMSO/CCl 3
Scheme 1
O OH
Reference
[1] A. R. Katritzky, X. L. Cui, B. Yang and P. J. Steel, J. Org. Chem., 1999, 64, 1979–1985。
[2] Peter Din′er and Mohamed Amedjkouh, Org. Biomol. Chem,2006,4,2091-2096
R

Symposium 2
Phosphorus Coordination Compounds
and their Use as Catalysts

KL-5
DESIGN AND SYNTHSIS OF SPIRO PHOSPHORUS LIGANDS FOR
ASYMMETRIC CATALYSIS
Qi-Lin Zhou
State Key Laboratory and Institute of Elemento-organic Chemistry, Nankai University
Tianjin 300071, China
Chiral phosphorus ligands play a crucial role in transition-metal-catalyzed asymmetric reactions,
and many effective chiral phosphorus ligands have been synthesized over the past few decades.
Since there are no universal ligands and catalysts for asymmetric transformations and the
enantioselectivity is substrate-dependent in most asymmetric reactions, the search for efficient
chiral ligands in terms of high enantioselectivity, and high turnover number (TON) remains one of
the most important goals in asymmetric catalysis. Recently, we developed a new class of
phosphorus ligands with chiral spirobiindane and spirobifluorene backbones and demonstrated they
are highly efficient for number of asymmetric transformations. In this presentation we will discuss
our new investigations on the development of these novel chiral spiro phosphorus ligands and their
applications in transition-metal-catalyzed asymmetric hydrogenation and carbon-carbon bond
forming reactions.
O
O P
R
N
R
PAr 2
PAr 2
O
P OR
O
125
O
P
O
R P R
Acknowledgment
We thank the National Natural Science Foundation of China, and the Ministry of Education of
China for financial support.
References
(1) Shi, W.-J.; Zhang, Q.; Xie, J.-H.; Zhu, S.-F.; Zhou, Q.-L. J. Am. Chem. Soc. 2006, 128, 2780.
(2) Duan, H.-F.; Xie, J.-H.; Shi, W.-J.; Zhang, Q.; Zhou, Q.-L. Org. Lett. 2006, 8, 1479.
(3) Duan, H.-F.; Jia, Y.-X.; Wang, L.-X.; Zhou, Q.-L. Org. Lett. 2006, 8, 2567.
(4) Cheng, X.; Xie, J.-H.; Li, S.; Zhou, Q.-L. Adv. Synth. Catal. 2006, 348, 1271.
(5) Hou, G.-H.; Xie, J.-H.; Wang, L.-X.; Zhou, Q.-L. J. Am. Chem. Soc. 2006, 128, 11774.
(6) Zhu, S.-F.; Xie, J.-B.; Zhang, Y.-Z.; Li, S.; Zhou, Q.-L. J. Am. Chem. Soc. 2006, 128, 12886.
PAr 2
PAr 2

KL-6
SYNTHESIS AND APPLICATION OF NEW P-CHIRAL PHOSPHINE LIGANDS
Tsuneo Imamoto
Department of Chemistry, Faculty of Science, Chiba University, Yayoi-cho, Inage-ku Chiba 263-8522, Japan
126

KL-15
MY EXCURSION TO THE CHEMISTRY OF STABLE DIRADICALS:
DIPHOSPHETANEDIYLES
Edgar Niecke
Anorganisch-Chemisches Institut der Universität Bonn, Germany
Diradicals (diradicaloids) containing elements of the p-block [1] are structures in their own right,
since they are stable entities in contrast to the plethora of highly unstable diradicals discussed in
organic chemistry[2]. They promise extraordinary properties due to their peculiar electronic
structure[3].
Within this report an overview on the structure and reactivity of 1,3-diphosphetane-2,4-diyles 1
will be given. Investigation will be presented in detail under following subjects:
i) the photochemical and thermal interconversions involving valence isomers 1-4
ii) the chemical behaviour of 1 as a crypto-carbene 3
iii) the coupling of diradical 1 via p/d block metals and organic spacer fragments: achieving an
electronic communication between the unpaired electrons through the spacer 5
iv) the reactivity towards acids or bases, to yield the ions 6,8
v) the electron transfer reactions leading to persistent radical cations 7, and temporarily
traceable anionic radicals 9, as well as subsequent reactions.
Furthermore, the synthesis and reactivity of a radical anion containing the
1,4-diphosphabutandiene 4 skeleton will be discussed in detail.
RP PR RP PR RP PR RP PR RP PR
1 3
RP PR RP
RP PR RP PR
RP
2
Spacer
4 5
127
6 7
RP PR
8 9
Reference
[1] a) E. Niecke, A. Fuchs, F. Baumeister, M. Nieger, W.W. Schoeller, Angew. Chem. Int. Ed. 1995, 34, 555; (b)
G.Bertrand, (c) H. Sugiyama, S. Ito, M. Yoshifuji, Angew. Chem. Int. Ed.. 2003, 42, 3932; (d)
[2] W.T. Borden, H. Iwamura, J.A. Berson (1994), Acc. Chem. Res., 27, 109.
[3] (a) M.Sebastian, M. Nieger, W.W. Schoeller, E.Niecke, Chemistry; (b) W.W. Schoeller, E.Niecke, J Phys. Chem.
submitted.

KL-17
INNOVATIVE CHIRAL PHOSPHORINES FOR
HYDROGENATION AND HYDROFORMYLATION
Xumu Zhang
Department of Chemistry, Penn State University, University Park, PA 16802, xumu@chem.psu.edu, +1-814-880-4373
(phone). Since 1/1/07, Professor II, Center for Molecular Catalysis, Department of Chemistry and Chemical
biology, Rutgers University, NJ 08854, xumu@rutgers.edu
The research in my group addresses fundamental and practical problems in this field by
developing a diverse set of chiral ligands which combine with transition metals to form effective
catalysts. We are also inventing new metal-catalyzed reactions through screening of reaction
conditions. Our technologies have been used by pharma and fine chemical companies
internationally for the synthesis of chiral pharmaceutical products in a highly efficient,
cost-effective and environmentally compliant way. Selected chiral ligands developed by us are
TunePhos, Binaphane, TangPhos, Binapine, and DuanPhos. Transitional metal complexes (Ru,
Rh, Pd and Ir) with our chiral ligands are highly enantioselective (up to 99%ee) and active (up
to 100,000 turnovers) catalysts for hydrogenation of many types of ketones, imines and olefins.
Commercial scale of several ligands have been produced for practical synthesis if chiral
molecules. Recently, we have developed YanPhos for asymmetric hydroformylation. Up to
99% ee have been achieved. These methods provide useful ways to make chiral amines,
alcohols, alpha and beta-amino acids, acids, aminoalchohols and other chiral building blocks.
128

KL-30
PHOSPHORUS LIGANDS DESIGN FOR COORDINATION CHEMISTRY
AND CATALYSIS
P.L. Floch
Laboratoire « Hétéroéléments et Coordination UMR CNRS 7653, Département de Chimie,Ecole Polytechnique, 91128
Palaiseau Cedex, France Email: lefloch@poly.polytechnique.fr
The structural and electronic design of ligands is crucial in the elaboration of highly performant
and selective catalysts. Over the last few years, most of our activity focused on the synthesis of
phosphorus ligands that exhibit a strong π-accepting capacity 1 as well as a on the synthesis of
mixed architectures featuring different heteroatoms (P-olefin ligands, 2 P~N, 3 P~S 4 heteroditopic
ligands). Many efficient catalytic systems were developed for different transformations such as
hydroformylation, 5 C-C and C-B and C-N coupling reactions. 6 A part of the lecture will focus on
the design of efficient palladium based catalysts for the allylic allylation of primary amines using
allylic alcohol as substrate.
A detailedinvestigation of the catalytic cycle through DFT calculations allowed the design of a
very simple and efficient catalyst and shed some light on related catalytic transformations such as
the hydroamination of olefins and dienes. 7
The second part of the lecture will focus on the use of mixed P~N and P~S ligands in the
oligomerization of ethylene into butene 8 and the activation of small molecules and C-H bonds
respectively.
References
[1] Le Floch, P.; Coord. Chem. Rev. 2006, 627.
[2] Thoumazet, C.; Ricard, L.; Grutzmacher, H.; Le Floch,P. Chem. Commun. 2005, 1592.
[3] Boubekeur, L. ; Ulmer, S. ; Ricard, L. ; Mézailles, N. ; Le Floch, P. Organometallics, 2005, 25, 315.
[4] Doux, M. ; Ricard, L. ; Le Floch, P. ; Jean, Y. Organometallics, 2005, 24, 1608.
[5] Mora, G. ; van Zutphen, S. ; Thoumazet, C.; Le Goff, X. F.; Ricard, L.; Grutzmacher, H. Le Floch,
P.,Organometallics, 2006, 25, 5528.
[6] M. Doux, N . Mézailles, M. Melaimi, L. Ricard, P. le Floch, Chem. Commun. 2002, 1566.
[7] Piechaczyk, O.; Thoumazet, C.; Jean, Y.;Le Floch, P. J. Am. Chem. Soc. 2006, 128, 14306.
[8] Buchard, A. ; Auffrant, A. ; Klemps, C. ; Vu-Do, L. ; Boubekeur, L. ; Le Goff, X. F. le Floch, P.,
129

IL-8
AMBIPHILIC PHOSPHINE/BORANE DERIVATIVES: SYNTHESIS AND
COORDINATION PROPERTIES
S. Bontemps a , G. Bouhadir a , K. Miqueu b , L. Maron c , D. Bourissou a
a
Laboratoire Hétérochimie Fondamentale et Appliquée (UMR 5069), Université Paul Sabatier, 118 route de Narbonne,
F-31062 Toulouse cedex 4, France, Fax: +33 (0)5 6155 8204, Email: dbouriss@chimie.ups-tlse.fr.
b
Equipe de Chimie-Physique (UMR 5254-IPREM), Avenue de l'Université, BP 1155
F-64013 Pau cedex, France.
c
Laboratoire de Physique et Chimie des Nano-Objets (UMR5215), INSA, 135 avenue de Rangueil,
F-31077 Toulouse Cedex, France.
Lewis acids are frequently involved in organometallic chemistry as co-catalysts. In particular,
their ability to activate complexes via ligand abstraction is well-recognized. 1 The possibility for
Lewis acids to behave as ligands for transition metals has also been demonstrated, 2,3 although this
coordination mode remains very rare. In this perspective, we are investigating ligands combining
Lewis base and Lewis acid coordination sites, so-called ambiphilic ligands.
Lewis
base
spacer
Lewis
acid
ML n
130
[ML n ]
The synthesis, structure and coordination properties of mono- and di-phosphine-borane ligands 1
and 2 will be presented. 4 The different coordination modes adopted by these ambiphilic ligands will
be discussed, from both experimental and theoretical viewpoints.
R 2 P BR' 2
1
B
R'
R 2 P PR 2
2
R 2 P BR' 2
L n M X
R 2 P
R 2 P
R 2 P BR' 2
Acknowledgements: Thanks are due to the CNRS, UPS, and the French Ministry of Research and
New Technologies (ACI JC4091, ANR BILI) for financial support of this work and to IDRIS
(CNRS, Orsay, France) for calculation facilities.
References
1aW. E. Piers et al Organometallics 1995, 14, 4617. 1bG. Erker et al J. Am. Chem. Soc. 2004, 126, 11046. 1cD. Zargarian
et al J. Am. Chem. Soc. 2004, 126, 8796.
2For a triphenylalane complex, see: J. M. Burlitch, R. E. Hugues et al Inorg. Chem. 1979, 18, 1097.
3For the first structural characterization of a borane complexes, see: A. F. Hill et al Angew. Chem. Int. Ed. 1999, 38,
2759.
4aS. Bontemps, H. Gornitzka, G. Bouhadir, K. Miqueu, D. Bourissou Angew. Chem. Int. Ed. 2006, 45, 1611. 4bS.
Bontemps, G. Bouhadir, K. Miqueu, D. Bourissou J. Am. Chem. Soc. 2006, 128, 12056.
BR'
ML n
M Ln

IL-11
SYNTHESIS AND ASYMMETRIC CATALYSIS OF NEW CHIRAL TETRADENTATE
AMINOPHOSPHINE LIGANDS
Yan-Yun Li, Zhen-Rong Dong, Wei-Yi Shen, Gui Chen, Xue-Qing Zhang, Hui Zhang , Jingxing Gao
State Key Laboratory of Physical Chemistry of Solid Surfaces, Department of Chemistry
Xiamen University, Fujian, P.R.China
For the past decades, chiral phosphine compounds are becoming the most important and popular
ligands in asymmetric catalysis. Recently, chiral mixed P, N-ligands have attracted considerable
attention because of the distinctly different characteristics of a “soft” phosphorus with π-acceptor
properties and a “hard” nitrogen atom acting as an σ-donor ability. The π-acceptor character of the
phosphorus atom can increase basicity and stabilize a metal center in a low oxidation state, while
the nitrogen σ-donor ability makes a weaker coordination to metal center and easily dissociates in
solution to afford a vacant site for the substrate coordination. This favorable combination displays
important rule during a catalytic cycle.
Several chiral tetradentate PNNP-type ligands with sp 2 -N and sp 3 -N were conveniently
synthesized by the condensation of o-(diphenylphosphino)benzaldehyde and appropriate chiral
diamine with 85-93% yield.
H H
N N
P Ph 2
Ph
3
P
Ph 2
Ph
H H
N N
P Ph 2
9
P
Ph 2
[ H ]
[ H ]
N
P
Ph 2
Ph
2
N
P Ph 2
H 2N NH 2
1
Ph
H 2N NH2
7
Ph Ph
N
P
Ph 2
8
N
P Ph 2
CHO
PPh2 131
H CH 3
H 2N NH 2
4
H 2N NH 2
10
N
H
N N
CH 3 H CH 3
N
[ H ]
P
Ph 2
P
Ph 2
P
Ph 2
P
Ph 2
5 6
[ H ]
H
N N
P
Ph2 P
Ph2
P
Ph2 11 12
Scheme 1 Synthesis of chiral PNNP ligands
Based on these mixed P, N-ligands, a family of chiral PNNP ligands with Ru (II), Rh (I) and Ir (I)
complexes have been prepared and fully characterized. These complexes have been proved to be
excellent catalyst precursors for the asymmetric transfer hydrogenation of a series of ketones using
2-propanol as hydrogen source, leading to the corresponding optical alcohols with up to 99% ee and
even the molar ratio of ketone to catalyst up to 10000: 1.
R 1
O
R 2
*
R 1
R 2
OH
chiral PNNP-M catalyst
+ +
16 examples up to 99% ee
Scheme 2 Asymmetric transfer hydrogenation of aromatic ketones
OH
H
N
N
H
P
Ph2 H
O

Chiral PNNP-Ir(I) complexes have been also used in the enantioselective redox reaction of
ketones and alcohols. In the presence of KOH, the oxidative kinetic resolution of several racemic
second alcohols gave the excellent enantioselectivity of up to 98% ee.
R 1
R 1
*
OH
OH
R 2
R 2
+ R +
1
+
Ir(I)-PNNP PNNP:
R 1
OH
O
R 2
R 2
Scheme 3 Oxidative kinetic resolution of racemic second alcohols
These results indicate that chiral tetradentate PNNP ligands represent a new class of mixed-P, N
organic ligands. They possess a versatile reactivity towards metal atoms and can provide better
control the coordination number and stereochemistry of the resulting metal complexes.
Continuation of studying on the electronic and steric properties will develop more effective
polydentate P, N-ligands and further expand their use in asymmetric catalysis.
References
[1] J.-X. Gao, T. Ikariya and R. Noyori, Organometallics, 15, 1087 (1996).
[2] H. Zhang, C.-B. Yang, Y.-Y. Li, Z.-R. Dong, J.-X. Gao, H. Nakamura, K. Murata and T. Ikariya, Chem. Commun.,
142 (2003).
[3] J.-S. Chen, Y.-Y. Li, Z.-R. Dong, B.-Z. Li and J.-X. Gao, Tetrahedron Lett., 45, 8415 (2004).
[4] Z.-R. Dong, Y.-Y. Li, J.-S. Chen, B.-Z. Li, Y. Xing and J.-X. Gao, Org. Lett., 7, 1043 (2005).
[5] Y.-Y. Li, X.-Q. Zhang, Z.-R. Dong, W.-Y. Shen, G. Chen and J.-X. Gao, Org. Lett., 8, 5565 (2006).
[6] Y. Xing, J.-S. Chen, Z.-R. Dong, Y.-Y. Li and J.-X. Gao, Tetrahedron Lett., 47, 4501 (2006).
The financial support from NSFC (20373056, 20423002) and Fujian PSTC (2005YZ1020) is
gratefully acknowledged.
+
132
O
OH
H
N
**
P
Ph2 N
H
P
Ph 2

IL-13
PHOSPHORUS CHEMISTRY & SUSTAINABLE DEVELOPMENT
Pascal Metivier
Rhodia, R&D for Phosphorous and Performance Derivatives Oak House, reeds Crescent Watford, WD24 4QP, UK
133

IL-14
PHOSPHINE AND PHOSPHINE-MIMIC COMPLEXES IN CATALYSIS
T. S. Andy Hor
Department of Chemistry, National University of Singapore, Singapore, 117543
Email: andyhor@nus.edu.sg
Phosphines are probably the most widely used ligands in supporting homogeneous catalysts.
They offer good σ and π donor and accepting properties and are easily tunable, electronically and
sterically. Unfortunately, they are also plagued by problems such as solution dissociation, aerial
oxidation and thermal degradation. There has been therefore a strong call for alternative ligands,
termed “phosphine mimics”, that share the strengths but not the weaknesses of phosphines. We
have recently embarked on a project to examine the viability of N,S-heterocyclic carbenes (NSHC)
as such mimics. 1 Early results on their chemical stability, structural integrity and catalytic activities
are promising. In this presentation, we shall summarize our latest findings especially on the
syntheses and structural elucidation of these mimicking ligands.(Figures below) We shall also take
a glimpse at the immediate prospect and challenges of this type of novel complexes in catalysis.
Acknowledgement: This work was carried out by the Ph.D. scholar Ms Swee-Kuan YEN and in
collaboration with my colleague Dr H. Vinh HUYNH. It is funded by NUS and A*Star of
Singapore.
References
S. K. Yen, L. L. Koh, F. E. Hahn, H. V. Huynh and T. S. A. Hor, Organometallics, 2006, 25, 5105.
134

IL-40
SYNTHESIS AND CHEMISTRY OF METALLABENZYNE
Tingbin Wen, a, * and Guochen Jia b, *
a
The College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, 361005, P. R. China. Email:
chwtb@xmu.edu.cn
b
Department of Chemistry, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong
Kong, P. R. China. Email: chjiag@ust.hk
Tertiary phosphines, PR3, can alter electronic and steric properties over a very broad range by
varying R group. Thus they can act as supporting ligands in an exceptional wide variety of
organometallic compounds and constitute one of the most widely used ligands in organometallic
chemistry.
Following the reported work on the ruthenium vinylidene complexes RuCl2(=C=CHR)(PPh3)2
with the simplest tertiary phosphine PPh3 as ligand, which can be prepared conveniently from the
reaction of RuCl2(PPh3)3 with HC≡CR and act as an alternative to Grubbs’ catalysts for olefin
metathesis, we were tempted to prepare analogous osmium vinylidene complexes
OsCl2(=C=CHR)(PPh3)2 via similar preparative routes. Unexpectedly, the reaction of OsCl2(PPh3)3
(1) with HC≡CSiMe3 lead to the formation of the first metallabenzyne complex 2, which represents
a new class of organometallic compounds. Metallabenzynes are interesting because they are
structurally related to metallabenzenes and benzynes. We thus initiated a program directed toward
the synthesis and chemistry of metallabenzyne. This presentation will report some of our progress
in this field.
Cl
Cl
Cl
Cl
Cl
Cl
PPh 3
Os
PPh 3
Os
PPh 3
PPh 3 SiMe 3
PPh 3
NaCl HBF 4
PPh 3
Os
PPh 3
1
SiMe 3
CH 3
SiMe 3
2
5
Ar
( Ar = Ph,
p- tolyl )
CH 3
PPh 3
Cl
C
Cl
Os
C
C H
Ar
3
AgOTf
N
Br 2
Br 2
N
Br
Br
PPh 3
PPh 3
Os
PPh 3
N
N
H
C Ar
6
PPh 3
Os
PPh 3
7
Br
Br
135
(Ph 3P)Au R
CH 3
Et 3NHCl
R = Ph, p- tolyl,
SiMe 3, Bu n
SiMe 3
SiMe 3
2OTf-
2+
CH 3
NaBH 4
MeOH
K2CO3 Cl
Cl
PPh 3
Os
Ar
PPh 3
R
H
4
H
SiMe3 Me
H
N
Os
SiMe3 N
PPh 3
8
Ph3P Me
O H
N
Os
N
Ph3P 9
SiMe 3
CH 2Ar
+
OTf-
+ OTf-
CH 3

O-35
SYNTHESIS OF STRAINED-RING PHOSPHORUS HETEROCYCLES FROM
PHOSPHATRIAFULVENES AND PHOSPHAHEPTAFULVENES
Heydt, H. Bergsträber, U. Hofmann, M.A. Werner, S. Regitz, M
Department of Chemistry, Technical University of Kaiserslautern
67663 Kaiserslautern, Germany
The developments in the chemistry of low-coordinate phosphorus compounds are essentially
dominated by compound possessing P/C double bonds. In accord with the Pauling
electronegativities, the carbon atom in such a bond carries partial negative charge and the
phosphorus atom partial positive charge. This polarization is reinforced in the
phosphapentafulvenes by the formation of an aromatic cyclopentadienide increment.
Phosphaalkenes with an inverse electron distribution are also known. They can be realized from
phosphatriafulvenes or phosphaheptafulvenes when the positive charge is stabilized in a
Hückelaromatic cation. The contribution deals with the synthesis and reactivity of these interesting
phosphaalkenes with emphasis of the inverse electron distribution. Evidence for the inverse charge
distribution will be presented by their reaction with nucleophiles, electrophiles and phosphaalkynes,
from their spectroscopic data, as well as from crystallographic analysis and from ab initio
calculations .[1,2] Furthermore, many of these result are previously unreleased in chemical journals.
Reference
[1] M. A. Hofmann, PhD Thesis; Technical University of Kaiserslautern: Germany, 2000
[2] S Werner, PhD Thesis; Technical University of Kaiserslautern: Germany, 2002
136

O-36
HIGHLY FUNCTIONALISED PHOSPHORUS LIGANDS: SYNTHESIS AND DIVERSE
COORDINATION CHEMISTRY
Martin B. Smith
Department of Chemistry, Loughborough University, Loughborough, Leics, LE11 3TU, UK.
E-mail: m.b.smith@lboro.ac.uk
Highly functionalised phosphorus(III) ligands continue to find many diverse applications in areas
such as transition-metal catalysed reactions, organic transformations, supramolecular chemistry,
medicinal chemistry and as selective metal extractants. 1-3 This oral paper will present some of our
recent developments regarding new mixed donor atom terdentate (P2O-, PN2-) and tetradentate
(PN3-, PN2O-, P2N2) phosphines derived from readily available Ph2PCH2OH (1), 2-Ph2PC6H4CHO
(2) or 2-Ph2PC6H4NH2 (3) precursors. Synthetic details to these multidentate phosphines, their
diverse late-transition metal coordination chemistry and unusual reactivity will also be given. 4,5
OH
Ph
P Ph
Ph
CHO
P Ph
(1) (2) (3)
P 2O-, P 2N 2ligands
PN 3-, PN 2Oligands
137
Ph
NH 2
PN 2ligand
P Ph
References
1. J. H. Downing and M. B. Smith, Phosphorus Ligands in, Comprehensive Coordination Chemistry II, Ed. A. B. P.
Lever, Elsevier, Oxford, 2003, vol. 1, 253.
2. S. E. Dann, S. E. Durran, M. R. J. Elsegood, M. B. Smith, P. M. Staniland, S. Talib and S. H. Dale, J. Organomet.
Chem., 2006, 691, 4829.
3. M. B. Smith, S. H. Dale, S. J. Coles, T. Gelbrich, M. B. Hursthouse and M. E. Light, CrystEngComm., 2006, 8, 140.
4. M. R. J. Elsegood, M. B. Smith and P. M. Staniland, Inorg. Chem., 2006, 45, 6761.
5. S. E. Durran, M. R. J. Elsegood, S. R. Hammond and M. B. Smith, submitted for publication.

O-37
P* CHIRAL AMINOPHOSPHINE COMPLEXES OF COPPER (I): SYNTHESIS AND
X-RAY STRUCTURAL CHARACTERIZATION
T. Arun Luiz a , Babu Varghese b and M. N. Sudheendra Rao a *.
a Department of Chemistry, Indian Institute of Technology Madras, Chennai -600036 (India).
b Sophisticated Analytical Instruments Facility, Indian Institute of Technology Madras, Chennai - 600036 (India).
Chemistry of phosphine complexes with copper (I) is an actively investigated area. Different
structural types with varying coordination number at copper have been realized. Copper (I)
phosphine complexes find applications in variety of fields which include medicine, catalysis,
material science etc [1-3]. The use of ancillary ligands such as bipyridyl etc is known to influence
stereochemistry and properties of the resultant complex significantly. Aminophosphines which are a
novel class of phosphorus(III) ligands carrying one or more amino substituents on phosphorus have
not been adequately employed as ligands in metal chemistry. P* chiral aminophosphines, are even
much less investigated.
In this investigation, P* chiral aminophosphine, (Diisopropylamino)
(Morpholino)(Phenyl)Phosphine recently synthesized by us has been made use of in the reactions
with copper(I) halide as precursors . Bipyridyl has also been used as ancillary ligand in some of
the reactions. Both monomeric and dimeric copper (I) complexes with different coordination
number at copper have been isolated and characterized by using spectral and X-ray structural
methods. X-ray structures reveal strong Copper-Phosphorus bonds ( ~ 2.18 Å) and different
roles played by the halide ligand. The details of this study will be presented in this poster.
References
1. Marzano, C. ; Pellei, M. ; Alidori, S. ; Brossa, A. ; Lobbia, G. G.; Tisato, F. ; C. Santini, J .Inorg. Biochem., 2006,
100, 299.
2. Grodzicki, A.; Lakomska, I. ; Piszczek , P.; Szymanska, I.; Szlyk., E. Coord. Chem. Rev., 2005, 249, 2232.
3. Cormick, T. M.; Jia, W. L ; Wang, S Inorg. Chem., 2006, 45, 147.
138

O-38
PHOSPHORUS TRIVALENT REAGENTS: EFFICIENT TOOLS FOR
MULTICOMPONENT AND ORGANOCATALYTIC REACTIONS
David Virieux*, Anne Françoise Guillouzic, Henri-Jean Cristau, Jean-Luc Pirat
Laboratoire d’Architectures Moléculaires et Matériaux Nanostructurés
Institut Charles Gerhardt, UMR 5253 – ENSCM
8 rue de l’Ecole Normale - 34296 Montpellier cedex 5 – France
Short synthetic methods for the preparation of highly functionalized compounds are still a
challenge for organic chemists. Thus, with respect to their productivity, convergence and atom
economy, multicomponent and organocatalytic reactions occupy an outstanding position, deserving
our interest in the field of organophosphorus chemistry.According to the nature of the nucleophilic
trivalent phosphorus reagents, we can drive reactions towards organocatalytic systems 1,2 or tandem
multicomponent processes leading to a wide variety of extremely diversified structures.
R1 = Ph
R2 , R3 R
= NEt2 R = p-CF3-C6H4 Yield 30-33%
1 = Ph
R2 , R3 = NEt2 R = p-CF3-C6H4 Yield 30-33%
R1 = R2 = Ph
R3 R
= NEt2 Yield 56%
1 = R2 = Ph
R3 = NEt2 Yield 56%
R
EWG
O
PPhNEt 2
R= Ar ou alkyl
R
R
OH
EWG
O
1 = Ph
R2 = Ph, OEt
R3 R= Ar ou alkyl
R
= NEt2 , OEt
R
OH
* EWG
*
O
Yield 11-81%
1 = Ph
R2 = Ph, OEt
R3 = NEt2 , OEt
*
*
Yield 11-81%
OH
PPh 2
Ar
OH
CO 2 Et
O
PPh 2
CO2Me R
Cl
PPh3 _
⊕
OH
Cl
CN
R
Cl
PPh3 _
PR
⊕
1R2R3 = PPh3 R = p-CF3-C6H4 Yield 48%
PR1R2R3 CO2Me R
Cl
PPh3 = PPh3 R = p-CF3-C6H4 , p-MeC6H4 p-NO2-C6H4 , Ph
Yield 54-81%
_
⊕
OH
Cl
CN
R
Cl
PPh3 _
PR
⊕
1R2R3 = PPh3 R = p-CF3-C6H4 Yield 48%
PR1R2R3 = PPh3 R = p-CF3-C6H4 , p-MeC6H4 p-NO2-C6H4 , Ph
Yield 54-81%
P R2 R 1
晻
P R2 R 1
晻
P R2 R 1
晻
R 3
R 3
R 3
139
R 1
R 1
N
R 1
R 1
O
(EWG = CO 2 Me, CO 2 Et, COMe, CN)
EWG
PR3 = P(n-Bu) 3
R1 EWG
PR3 = P(n-Bu) 3
R = H, Et
Yield 4-57%
1 = H, Et
Yield 4-57%
X H
X
X
N
EWG
R 1 R HN
1 HN
O
S
O R1
O R1
EWG
PR 3 = PPh 3
X = C, CH, N
H
Yield 16-94%
OH
EWG
PR3 = P(n-Bu) 3
R = H, Me
R1 PR3 = P(n-Bu) 3
R = H, Me
R = H, OMe
Yield 34-59%
1 = H, OMe
Yield 34-59%
PR 3 = PPh 3
R = Ph
Yield 7-30%
PR3 = P(n-Bu) 3
R1 PR3 = P(n-Bu) 3
R = H, Me
Yield 33-56%
1 = H, Me
Yield 33-56%
The influence of subtituents on the phosphorus atom in combination with the appropriate starting
materials was completely rationalized allowing to predict the course of the reactions.
Reference
[1]. D. Virieux*, A.-F. Guillouzic, H.-J. Cristau, Tetrahedron, 2006, 62, 3710-3720.
[2]. D. Virieux*, A.-F. Guillouzic, A. Fruchier, Heteroatom Chem., 2007, in press.

O-39
BISDITHIOPHOSPHONIC ACIDS IN METAL COMPLEX FORMATION REACTIONS
Il’yas S. Nizamov 1, 2 , Yevgeniy M. Martiyanov 1 , Il’nar D. Nizamov 3 , Alfiya N. Gataulina 1 , Rafael A. Cherkasov 1
1
Kazan State University, Kremlievskaya Str., 18, Kazan, 420008, Russia,e-mail: Ilyas.Nizamov@ksu.ru
Ilyas.Nizamov@ksu.ru
2
A.E. Arbuzov Institute of Organic and Physical Chemistry,Arbuzov Str., 8, Kazan, 420088, Russia,
3 Tatar State Humanitarian Pedagogical University, Tatastan Str. 2, Kazan, 420021, Russia
There is a considerable interest in metal derivatives of phosphorus thioacids due to their use in
metal complex catalysis. We have previously prepared zinc and nickel derivatives of
bisdithiophosphonic acids obtained on the basis of 2,4-dimethyl-1,3,2,4-dithiadiphosphetane-2,4-disulfide
[1]. In continuation of this work we have involved in the reactions of
formation of bisdithiophosphonic acids such 1,3,2,4-dithiadiphosphetane-2,4-disulfides as
4-ethoxyphenyl, 3,5-di-tret-butyl-4-hydroxyphenyl and 4-phenoxyphenyl homologues of
Lawesson’s reagent and such diols as 1,3-propanediol, 1,4-butandiol, neopentyl glycol,
bis(2-hydroxyethyl)sulfide and tri(ethylene glycol). These reactions proceed at 50-60 o C for 1-2 h in
benzene solutions. The 31 P NMR spectra of bisdithiophosphonic acids obtained show singlets at P
86-87 ppm.
Ar-P P-Ar + X
OH
OH
50-60
Ar-P
SH
O
HS
O
P-Ar
X
o S
S
S
S
C, 1-2 h
C
6
H
6
S S
Ar = 4-MeOC
6
H
4
, 4-EtOC
6
H
4
, HO
,
; X = , , ,
140
O O
To obtain metal complexes of bisdithiophosphonic acids we have used two approaches. One of
them involves the previous in situ preparation of the corresponding bisammonium salts of these
thioacids ( P 107 ppm) and their following subsitution reaction with Nickel(II) nitrate or zinc
chloride. Other method of synthesizing similar complexes was based on the refluxing of mixture of
bisdithiophosphonic acids with metal oxides such as Cobalt(II), Copper(II), Nickel(II) and Zinc
oxides in benzene suspensions for 11-25 h with evaluation of water formed. Metal complexes of
bisdithiophosphonic acids were isolated as yellow powders. The 31 P NMR spectra of these
complexes reveal signals at P 96-104 ppm. In the IR spectra bands of valence vibrations of the
-1
P=S and P-S bonds of complexes obtained are mixed and revealed in the region of 560 cm that
suggest a chelating behavior of the ligands.
Reference
[1] Kutyrev G.A., Korolev O.S., Cherkasov R.A., Pudovik A.N., Safiullina N.R., Yarkova E.G., Lebedeva O.Ye., Zh.
Obsch. Khim. (Russ.), 1986, 56, 1227.

O-40
SYNTHESIS AND BIOLOGICAL EVALUATION OF A HIGHLY REACTION Zn(II)
MONONUCLEAR COMPLEX FOR PHOSPHODIESTER CLEAVAGE
Chao Li a , Ren-Zhong Qiao a,b *, Yu-Fen Zhao b *
a b
Department of Pharmaceutical Engineering, Beijing University of Chemical Technology, Beijing 100029, China. The
Key Laboratory of Bio-organic Phosphorus Chemistry and Chemical Biology, Ministry of Education,
There is an increasing interest in the realisation of small and robust artificial DNA hydrolytic
agents for their potential applications not only in molecular biology but also in the development of
new drugs, recently. [1] Many nucleases are metalloenzymes. Among the physiologically relevant
metal ions, Zn (II) is probably the best suited metal ion for the development of artificial
metallonucleases. [2] However, its reactivity is somewhat lower than that of the other commonly
employed transition-metal ions, [3] especially mononuclear Zn (II) complexes. [4] We expect that the
catalytic activity of the small molecular Zn (II) complexes can be enhanced through some
modificators. Here, we first report synthesis, characterization and biological evaluation of a novel
class of Zn (II) complexes which contain oligopolyamide and bis(2-benzimidazolylmethyl)amine
conjugated by flexible linker. In a detailed set of experiments, we find that the novel Zn (II)
complexes can hydrolyze duplex DNA efficiently, bearing some selectivity.
O 2 N
N
CH 3
O
H
N
N
CH 3
O
n
H
N
n=1,2 or 3
O
HN
N
HN
N
N
Zn ClO 4
ClO 4
Figure1. The novel nucleases and gel electrophoresis of cleavage reaction of pUC18 DNA
We found optimal condition of cleavage reaction through a series of optimize experiment,
including pH value, concentration, time and temperature. The preliminary biological activity studies
showed that the efficient hydrolysis of plasmid DNA was observed at lower reaction concentration
and short time. In contrast to the complexes without oligopolyamide, the minimum of reaction
concentration and time decreased apparently in the presence of the novel Zn (II) complex.
Interestingly, at a high reaction concentration (1.2mM), Zn (II) complex converted the plasmid
DNA to a new band.
References
1. Livieri, M.; Mancin, F.; Tonellato, U.and Chin, J. Chem. Commun., 2004, 2862-2863.
2. Boseggia, E.; Gatos, M.; Lucatello, L.; Mancin, F.; Moro, S.; Palumbo, M.; Sissi, C.; Tecilla, P.; Tonellato, U.and
Zagotto, G. J. Am. Chem. Soc. 2004, 126, 4543-4549.
3. Hegg, E. L.; Burstyn, J. N. Coord. Chem. ReV. 1998, 173, 133-165.
4. Basile, L. A.; Raphael, A. L.; Barton, J. K. J. Am. Chem. Soc. 1987, 109, 7550-7551. Project supported by the
National Natural Science Foundation of China (No. 20572008).
141
FormⅡ
FormⅢ
FormⅠ
new band
ctrl 0.05mM 2.2mM
4000
3500
3000
2500
2000
1500
1000
500

O-41
COMPLEXES OF CROWN-CONTAINING N-PHOSPHORYLTHIOUREAS
WITH Ni(II) CATION
F. D. Sokolov*, S. V. Baranov, N. G. Zabirov, R. A. Cherkasov
Kazan State University, Russia, Kazan, *E-mail: felix.sokolov@ksu.ru
Previously we have found, that interaction of N-phosphorylthioureas of common formula
RNHC(S)NHP(O)(OPr-i)2 (HL; R = Alk, Ar) with Ni(II) and Pd(II) cations affords square-planar
M (II) L2 chelates, having unusual 1,3-S,N-coordination of the ligands. The realization of alternative
coordination modes (1,3-S,N- vs. 1,5-S,O-) takes place due to higher degree of negative charge
delocalization in SCN-fragment in comparison with phosphorous-containing moiety SCNPO.
Strong field of conjugated 1,3-S,N-ligands leads to a gain in energy for square-planar complexes of
Ni(II) and Pd(II) cations. Accessory factor of 1,3-S,N-chelates stabilization is a forming of strong
intramolecular H-bonds RNH ... O=P.
O H
R'
P
N
R' N
H S
O
O
O
O
O
O
O
O
142
O
O
R'
R'
O
P
N
H
N
S M S
N
H
N R'
P
O R'
This work is devoted to the coordination properties of analog containing benzo-15-crown-5
moiety. Changing of the coordination mode form from 1,3-S,N in Ni (II) L2 chelates to 1,5-O,S in
six-coordinated complexes Ni(Dn)2L2, formed by interaction with donor ligands (Dn for example,
pyridine) makes it interesting as а base for molecular triggers design.
Reference
[ 1 ] F. D. Sokolov, N. G. Zabirov, L. N. Yamalieva, V. G. Shtyrlin, Ruslan R. Garipov, V. V. Brusko, A.Yu. Verat, S. V.
Baranov, Piotr Mlynarz, T.Glowiak, H.Kozlowski // Inorganica Chimica Acta. – 2006 .- V. 359, N. 7. – P. 2087–2096.
O
O
O
O
O

O-42
NOVEL HETEROCYCLIC P-LIGANDS: SYNTHESIS AND APPLICATION
IN Pt(II) COMPLEXES
György Keglevich, 1 Andrea Kerényi, 1 Melinda Sipos, 1 Annamária Balassa, 1
Beatrix Mayer 1 and Tamás Körtvélyesi 2
1
Department of Organic Chemical Technology, Budapest University of Technology and Economics, H-1521
Budapest,Hungary 2 Department of Physical Chemistry, University of Szeged, H-6701 Szeged, Hungary
We aimed at the development of special P-ligands. In one part of our project,
1,2,3,6-tetrahydrophopshinine oxides with an exocyclic P-function (e.g. 1) were prepared by the
AlMe3-mediated addition of >P(O)H species on the double-bond of 1,2-dihydrophosphinine oxides
in a diastereoselective manner. The P-heterocycles (e.g. 1) were then subjected to catalytic
hydrogenation to give 1,2,3,4,5,6-hexahydrophosphinine oxides (e.g. 2) again diastereoselectively.
The stereostructure and conformation of the products (e.g. 1 and 2) was evaluated on the basis of
theoretical calculations and spectroscopy. Double deoxygenation of 1 and 2 resulted in
diphosphines (3 and 4, respectively) that were suitable bidental P-ligands to form chelate complexes
5 and 6, respectively in reaction with (PhCN)2PtCl2.
O
Ph 2P
O
Ph 2P
Cl
P
O Ph
1
H 2
O
P
2
Ph
Me
Pd/C
Me
Cl3SiH pyridine
Cl3SiH pyridine
Ph 2P ..
Ph 2P ..
Cl
.. P
Ph
3
.. P
Ph
4
143
Me
Me
(PhCN) 2PtCl 2
ArH
(PhCN) 2PtCl 2
In another line of this research, achiral and chiral dibenzo[c.e][1,2]oxaphosphorins with different
P-functions (8) were synthesized that were converted to the corresponding platinum (II) complexes
(9). Ring opening of a dibenzooxaphosphorin (10) afforded
1-hydroxy-1'-diphenylphosphino-biphenyl (11) that was used in complexation with (PhCN)2PtCl2 to
furnish complex 12. A bidental P-ligand, as well as its complex were also developed.
7
O
P
Cl
PhMgBr
O
P
Ph
YH
N
ArH
1) PhMgBr
2) H2O 10 11
8
O
P
Y
Y = NEt2, H
OH
PPh2 (PhCN) 2PtCl 2
NH
ArH
Me
Ph ,
Me
(PhCN) 2PtCl 2
ArH
ArH
O
H
Me
Me
Cl
Cl
Ph 2P
Pt
Cl
Ph 2P
Pt
Cl
Cl
P
5
P
6
Ph
Ph
Cl Cl
O
Pt
O
P
P
Y Y
9
Me
Me
Ph
P Cl
Ph
OH
Cl
Pt
12
HO
P
Ph
Ph

O-43
DoM CHEMISTRY OF PHOSPHINIC AMIDES: SYNTHESIS OF LIGANDS AND THEIR
APPLICATION IN ROBUST HIGH PERFORMANCE CATALYSTS
D. Bradley G. Williams
Department of Chemistry, University of Johannesburg, PO Box 524
Auckland Park, 2006, South Africa. dbgw@rau.ac.za
Ligands are responsible for the selectivity of transition metal catalysed reactions. 1 Ligand design
is therefore an integral part in the improvement in reactivity and selectivity of metal catalysed
reactions.
Synthesis and catalysis
Directed ortho-metallation (DoM) 2 was used to synthesise a variety of ortho-substituted
phosphinic amides (2). With R2PCl as the electrophile, the resulting ligand showed excellent
activity in Pd catalysed Suzuki reactions with deactivated aryl bromides and some aryl chlorides.
Further manipulation
These substituted phosphinic amides were hydrolysed with HCl (aq), chlorinated (SOCl2) and
reacted with a range of aryl Grignard reagents to form highly functionalised unsymmetrical triaryl
phosphine oxides. These oxides can be reduced to the active phosphine ligands using trichlorosilane,
providing a facile route to highly functionalised P-chiral ligands.
Ph 2P Cl
E = electrophile
HNR2
H 2O 2
O
P
NR 2
s-BuLi
Electrophile
144
O
P
NR 2
E
1. HCl (aq)
2. SOCl2 3. R`MgX
1 2 3
Ligands as catalysts
for E = PCy 2 and PPh 2
Catalysis with
unsymmetrical
phosphine
O
P
R`
E
HSiCl 3
R
P E
The synthesis of ligands 2, their conversion into unsymmetrical ligands 4, and the application of
these ligands in catalysed transformations, with surprising results, will be discussed.
Reference
[1]van Leeuwen, P. W. N. M.; Homogeneous catalysis, Kluwer Academic Publishers, London, 2003.
[2]Sniekus, V.; Chem Rev., 1990, 90, 879
4

O-109
DESIGN, SYNTHESIS, AND APPLICATION OF PHOSPHAALKENES TO UNIQUE
PALLADIUM AND GOLD CATALYSTS
Shigekazu Ito, a Matthias Freytag, a Hongze Liang, a Katsunori Nishide, a Masaaki Yoshifuji a,b
a
Department of Chemistry, Graduate School of Science, Tohoku University,Aoba, Sendai 980-8578,
Japan
b
Department of Chemistry, The University of Alabama, Tuscaloosa 35487-0336, USA.
Phosphaalkenes bearing P=C double bond(s) display several intriguing properties affording novel
metal-complexes of unprecedented catalytic activities. We demonstrate here novel properties of
1,3-diphosphapropenes in relation to palladium chemistry and of phosphaalkene-gold complexes
showing specific catalytic activity. A stable 2-silyl-1,3-diphosphapropene 1 was prepared by
employing a 1-silyl-2-phosphaethenyllithium and its structure has already been discussed based on
the 31 P NMR spectroscopic, X-ray crystallographic, and theoretical data. The unsymmetrical P2
ligand 1 afforded the corresponding dichloropalladium(II) chelate complex which reveals
considerable catalytic activity in Sonogashira cross-coupling reactions [1].
Taking the π-electron accepting property of P=C double bond into account, phosphaalkenes are
expected as a suitable ligand for gold catalysts which might show high electrophilic affinity for
unsaturated carbon-carbon bonds. Indeed, we found that chlorogold(I) complexes bearing
phosphaalkenes 2–4 catalyze cycloisomerization of 1,6-enyne derivatives without activation by any
silver additives, indicating that the P=C structure, the aurophilic gold-gold contact, and the sulfur
atom may increase electrophilicity of the gold center. The gold-gold contact appeared to control
conformation of the ligand 2. Additionally, we employed some 1,3-diphosphapropenes for
formation of gold complexes which showed catalytic activity in a couple of intriguing molecular
transformations [2].
Mes*
P
SiMe 3
PPh 2
Mes*
P
Me
P
Mes*
Me Mes* P P Mes*
1
2
Mes* = 2,4,6-t-Bu3C6H2 3
Reference
[1] S. Ito, K. Nishide, M. Yoshifuji, Organometallics 2006, 25, 1424.
[2] M. Freytag, S. Ito, M. Yoshifuji, Chem. Asian J. 2006, 1, 693.
145
Ph Ph
Mes*
P
4
SMe
SMe

P-18
NOVEL 36- AND 38-MEMBERED P,N-CONTAINING CYCLOPHANES WITH LARGE
HYDROPHOBIC CAVITIES
D.V.Kulikov a , A.S.Balueva a , A.A.Karasik a , A.V.Kozlov a , Sh.K.Latypov a , O.N.Kataeva a , P.Lönnecke b ,
E.Hey-Hawkins b , O.G.Sinyashin a .
a
A. E. Arbuzov Institute of Organic and Physical Chemistry, Russian Academy of Sciences, Arbuzov str. 8, Kazan,
Russia, 420088. E-mail: culdim@mail.ru
b
Institut für Anorganische Chemie der Universität Leipzig, Johannisallee 29, D-04103 Leipzig, Germany. E-mail:
hey@rz.uni-leipzig.de
The novel 36- and 38-membered cage P,N-containing cyclophanes 1a-d and 2 a-c were obtained
in good yields in the course of the covalent self-assembly processes [1,2] in three-component
systems: primary phosphine-formaldehyde-diamine with the spacers containing three p,m,p- or
p,p,p-phenylene rings linked by one-atom bridges.
R
O
O
P
N
N
P
O
O
R
2
O
O
DMF, 110 C o
NH 2
NH 2
4 R-PH2 +
8 H2CO H 2N
H 2N
146
Me
Me
DMF or TolH
110 C o
Me
Me
R
P
N
N Me
R
P
N
N
1 a-d
P
R
R = (a), (b), (c), CH2 (d)
Fe
Me Me
2 a-c
The cavity of 1a may be described as two halves of a truncated rhombohedral prism, which are
moved apart by the m-dioxiphenylene fragments, whereas the macrocycle 2c shows a helical
structure in crystal; the volumes of internal hydrophobic cavities are about 130-140 Å 3 .
1a 2c
Cyclophanes 1a and 2c form inclusion complexes with DMF and benzene respectively; one of
the benzene molecules is encapsulated by the cavity of 2c both in crystal and in benzene solution.
2
R
P
Me
Me
Me
Me
Me
N
R
P
P
R
N

Financial support from Volkswagen Foundation, RFBR (No. 06-03-32754-a), Russian Science
Support Foundation and from President’s of RF Grant for the support of leading scientific
schools (No. 5148.2006.3) is gratefully acknowledged.
References:
1. A.S.Balueva, R.M.Kuznetsov, S.N.Ignat’eva et al.. Dalton Trans., 2004, 442
2. R.N.Naumov, A.A.Karasik, O.G.Sinyashin et al. Dalton Trans., 2004, 357.
147

P-20
PHOSPHORUS FUNCTIONALISED CARBENES: SYNTHESIS AND
COORDINATION PROPERTIES
D.Morvan, J.J.Yaouanc, P.A.Jaffrès, J.F.Capon, P.Schollhammer, J.Talarmin, F.Gloaguen.
CEMCA, UMR CNRS 6521, Faculté des sciences et techniques, Université de Bretagne Occidentale, 6 avenue le
Gorgeu, 29238 Brest (France).
Metal complexes with N-Heterocyclic carbene (NHC) ligands are widely used in organometallic
chemistry1. NHC are well-known to be a good donor groups and the incorporation of functionality
is possible on the nitrogen atoms. We are interested in the synthesis of functionalised NHC with
functionality offering a new coordination centre or possessing hemilabile properties. In particular,
the functionalisation of NHC with phosphonate (A) leads us to develop original methods for their
synthesis. The organometallics complexes, incorporating the functionalised NHC, has been
synthesised following two pathways: 1- by using the silver carbene as intermediate2; 2- by using
the free carbene. According to the first method, several rhodium complexes has been synthesised
and characterised. The use of these rhodium complexes (B), as precursor of active catalysts for C-C
coupling, is still under investigation. Beside the chemistry of these rhodium complexes, we have
designed models of hydrogenase3a possessing either a phosphite (complex C) or a carbene ligand3b
(D). These complexes have been fully characterised by X-ray diffraction and by electrochemistry
methods. These results encourage us to study model of hydrogenase having functionalised NHC as
ligand.
References
[1](a) Bourissou, D.; Guerret, O.; Gabbaï, F. P. ; Bertrand G. Chem. Rev. 2000, 100, 39. (b) Herrmann, W. A.Angew.
Chem. Int. Ed. 2002, 41, 1290. (c) Arduengo, A.J. III.Acc. Chem. Res. 1999, 32, 913.
[2] Wang, H. M. J.; Lin I. J. B. Organometallics 1998, 17, 972.
[3] (a) Capon, J.-F.; Gloaguen, F.; Schollhammer, P.; Talarmin, J.; J. Coord. Chem. Rev. 2005, 249, 1664. (b)Capon,
J.-F.; El Hassnaoui, S.; Gloaguen, F.; Schollhammer, P.; Talarmin, J. ; Organometallics ; 2005; 24(9);2020-2022.
148

P-22
EXTRACTION PROPERTIES OF 1,10-DA-18-CROWN-6, MODIFIED BY EXOCYCLYC
CHELATING GROUPS
Felix D. Sokolov,* Maria G. Babashkina, Damir A. Safin,
Nail G. Zabirov, Rafael A. Cherkasov
A.M. Butlerov Chemical Institute, Kazan State University, 420008, Kremlevskaya str. 18, Kazan, Russia; e-mails:
felix.sokolov@ksu.ru
Modification of macrocycles with pendant chelate units affords new types of selective extraction
agents and ion receptors. Extraction of potassium picrate from D2O by CDCl3 solution of a complex
[{Cu(PPh3)2}2L] leads to almost quantitative formation of complex [K{Cu(PPh3)2}2L] + Pic - . The
extraction is insignificant for Li + and Na + cations and formation of the complexes can not be fixed
by NMR method. Crown-containing thiourea H2L shows no selectivity in the similar conditions.
O
O
P NH O O
S C N N
S O O
H 2L
O
HN P
C
S
S
O
149
Ph Ph
O
O
P N O O
Ph
S
P
Cu
Ph
P
Ph
Ph
S C N N C S
Cu
S
Ph
P
Ph
Ph P
PhPh
Ph
O O
Cu(PPh3) 2L
N P
O
O
This research was supported by BRHE 2004 (№ Y2-C-07-02), RFBR (03-03-32372-a,
03-03-96225-r2003tatarstan_a) grant programs.

P-26
CHIRAL SPIRO MONOPHOSPHITES FOR Rh-CATALYZED ASYMMETRIC
ADDITION OF ARYLBORONIC ACIDS TO ALDEHYDES, KETONES AND IMINES
Hai-Feng Duan, Shou-Fei Zhu, Yi-Xia Jia, Qi-Lin Zhou*
State Key Laboratory and Institute of Elemento-organic Chemistry, Nankai University
Tianjin 300071, China.
The transition-metal-catalyzed asymmetric addition of aryl organometallic reagents to aldehydes,
ketones and imines is a very attractive research topic because the products, chiral alcohols and
amines, are important intermediates for the synthesis of biologically and pharmceutically active
compounds. However, the highly enantioselective examples in this significantly useful reaction are
quite limited. The arylboronic acids are ideal organometallic reagents for this important
transformation due to their low cost, low toxicity, stability toward air and moisture, and tolerance to
a variety of functional groups. We herein disclose the highly enantioselective addition of
arylboronic acids to aldehydes, ketones and imines catalyzed by the rhodium complexes of spiro
monophosphite ligands 1. This approach extends the scope of the asymmetric addition of
arylboronic acids and provides a practical access to the synthesis of enantiomer-enriched alcohols
and amines.
OH
HO
R
O
R'
+
R = aryl, alkenyl
R' = H, CF 3, CO 2Bn
Ar 1
1.PCl 3 /NEt 3
2. ROH/NEt 3
(S)-SPINOL (S)-1
ArB(OH) 2
N Ts + Ar 2 B(OH) 2
O
P
O
R
[Rh] (1 mol%)
(S)-1e (2.1 mol%)
KF (2 equiv)
Toluene/H2O (1/1), 0°C
[Rh] (3 mol %)
(S)-1c (6 mol%)
KF (4 equiv)
Toluene/H 2O (1/1), 35 °C
150
a: R = Et
b: R = t Bu
c: R = Ph
d: R = 1-Naphthy
e: R = 2-Naphthy
OH
*
R Ar
R'
up to 93% ee
Ar 1
Ar 2
N
H
Ts
up to 96% ee
f: R = 4-MeOPh
g: R = 4-CF 3Ph
h: R = 2,6-DiMePh
i: R = 2-MeOPh
j: R = Phenanthrene
Acknowledgment: We thank the National Natural Science Foundation of China, and the Ministry of
Education of China for financial support.
References:
(1) Hayashi, T.; Yamasaki, K. Chem. Rev. 2003, 103, 2829.
(2) Duan, H.-F.; Xie, J.-H.; Shi, W.-J.; Zhang, Q.; Zhou, Q.-L. Org. Lett. 2006, 8, 1479.
(3) Duan, H.-F.; Jia, Y.-X.; Wang, L.-X.; Zhou, Q.-L. Org. Lett. 2006, 8, 2567.

P-59
SYNTHESIS OF O,O-DIALKYL-2-OXO-2-(4-(SELENOMOR
PHOLINOSULFONYL)PHENYLAMINO)ETHYLPHOSPHONATE
Fang Wang B , Liming Hu A *, Xiaopeng Li A , Xuemei Xu A
a
College of Life Sciences and Bioengineering, Beijing University of Technology, Beijing 100022, China;
b
College of Science Beijing University of Chemical Technology,Beijing 100029, China
A series of O,O-dialkyl 2-oxo-2-(4-(selenomorpholinosulfonyl)phenylamino)ethylphosphonate
were synthesized by reactions of 2-chloro-N-(4-(selenomorpholinosulfonyl)phenyl)acetamide with
dialkyl phosphite in the presence of sodium hydride. The structure of all new compounds has been
confirmed by 1 H NMR, 31 P NMR, IR, Mass spectroscopy and elemental analyses.
Science selenium was found to be an active center of glutathione peroxidase(GSH-Px), Which
can catalyze and decompose liquid hydroperoxide or hydrogen peroxide, the bioactivity of selenium
has developed rapidly 1-2 . Selenoorganic compound, such as Ebselen, was found the function against
biological damage caused in vivo by reactive hydroperoxides 3-7 . This increased a striking interest in
developing new selenoorganic compound for therapy. They have been potentially used in a variety
of fields varying from medicinal to agriculture application 8-10 . Recently, the antibiotic activity and
plant systemic activity of selenomorpholine derivatives were studied 11-12 . In our pervious work,
many selenoorganic compounds were synthesized and exhibited excellent pharmacological
effect 13-15 . In this work, we present synthesis of O,O-dialkyl-2-oxo-2-
(4-(selenomorpholino-sulfonyl)phenylamino)ethylphosphonate.
Reference
[1] Ji, Xiuling; Hu, Weixuan; Cheng, Jinping; et al Ecotoxicology and Environmental Safety. 64(2), 171-177(2006)
[2] Bansal, M. P.; Kaur, Parminder. Indian Journal of Experimental Biology. 43(12), 1119- 1129 (2005)
[3] Pearson, Jason K.; Boyd, Russell J. Journal of Physical Chemistry A. 110(28), 8979- 8985(2006)
[4] Filipovska, Aleksandra; Kelso, Geoffrey F.; Brown, Stephanie E. et al. Journal of Biological Chemistry.
280(25),24113-24126 (2005)
[5] Giurg, M.; Wojtowicz, H.; Mlochowski, J. Polish Journal of Chemistry. 76(4), 537-542(2002)
[6] Sattler, Wolfgang; Maiorino, Matilde; Stocker, Roland. Archives of Biochemistry and Biophysics. 309(2),
214-21(1994)
[7] Maiorino, Matilde; Roveri, Antonella; Coassin, Mariagrazia. et al. Biochemical Pharmacology. 37(11),
2267-71(1988)
[8] Smrkolj, Polona; Germ, Mateja; Kreft, Ivan. et al. Journal of Experimental Botany. 57(14), 3595-3600(2006)
[9] Robbins, Rebecca J.; Keck, Anna-Sigrid; Banuelos, Gary. et al. Journal of Medicinal Food. 8(2), 204-214 (2005)
[10] Pappas, Athanasios C.; Karadas, Filiz; Surai, Peter F.et al. Journal of Trace Elements in Medicine and Biology.
20(3), 155-160(2006)
151

P-105
SYNTHESIS OF CHIRAL SPIROBITETRALINE PHOSPHORAMIDITE LIGANDS
Hai-Feng Duan, Shou-Fei Zhu, Yi-Xia Jia, Qi-Lin Zhou*
State Key Laboratory and Institute of Elemento-organic Chemistry, Nankai University
Tianjin 300071, China.
The transition-metal-catalyzed asymmetric addition of aryl organometallic reagents to aldehydes,
ketones and imines is a very attractive research topic because the products, chiral alcohols and
amines, are important intermediates for the synthesis of biologically and pharmceutically active
compounds. However, the highly enantioselective examples in this significantly useful reaction are
quite limited. The arylboronic acids are ideal organometallic reagents for this important
transformation due to their low cost, low toxicity, stability toward air and moisture, and tolerance to
a variety of functional groups. We herein disclose the highly enantioselective addition of
arylboronic acids to aldehydes, ketones and imines catalyzed by the rhodium complexes of spiro
monophosphite ligands 1. This approach extends the scope of the asymmetric addition of
arylboronic acids and provides a practical access to the synthesis of enantiomer-enriched alcohols
and amines.
OH
HO
R
O
R'
+
R = aryl, alkenyl
R' = H, CF 3, CO 2Bn
Ar 1
1.PCl 3 /NEt 3
2. ROH/NEt 3
(S)-SPINOL (S)-1
ArB(OH) 2
N Ts + Ar 2 B(OH) 2
O
P
O
R
[Rh] (1 mol%)
(S)-1e (2.1 mol%)
KF (2 equiv)
Toluene/H2O (1/1), 0°C
[Rh] (3 mol %)
(S)-1c (6 mol%)
KF (4 equiv)
Toluene/H 2O (1/1), 35 °C
152
a: R = Et
b: R = t Bu
c: R = Ph
d: R = 1-Naphthy
e: R = 2-Naphthy
OH
*
R Ar
R'
up to 93% ee
Ar 1
Ar 2
N
H
Ts
up to 96% ee
f: R = 4-MeOPh
g: R = 4-CF 3Ph
h: R = 2,6-DiMePh
i: R = 2-MeOPh
j: R = Phenanthrene
Acknowledgment
We thank the National Natural Science Foundation of China, and the Ministry of Education of
China for financial support.
References
(1) Hayashi, T.; Yamasaki, K. Chem. Rev. 2003, 103, 2829.
(2) Duan, H.-F.; Xie, J.-H.; Shi, W.-J.; Zhang, Q.; Zhou, Q.-L. Org. Lett. 2006, 8, 1479

P-161
SYNTHESIS AND MECHANISM OF PHOSPHAISOQUINOLIN-1-ONES BY
Pd(II)-CATALYZED CYCLIZATION OF
O-(1-ALKYNYL)PHENYLPHOSPHONAMIDE MONOESTERS
Wei Tang and Yi-Xiang Ding*
Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences,
354 Fenglin Lu, Shanghai 200032, China
Isoquinolin-1-ones have gained considerable synthetic and pharmacological interest for a long
time because of their diverse bioactivities, Since there is a remarkable similarity in reactivity and
bioactivities between the carbon species and their phosphorus counterparts, 1 one can anticipate that
the phosphonamide analogues of isoquinolin-1-ones (i.e., phosphaisoquinolin-1-ones) would have
potential bioactivities similar to those of isoquinolin-1-ones.
The transition-metal-catalyzed cyclization of alkynes possessing a nucleophile in proximity to
the triple bond is an important process in organic synthesis, which can construct various
heterocycles in an efficient and atom economic way. 2 In this paper, we report a mild and efficient
palladium-catalyzed intramolecular cyclization of o-(1-alkynyl)phenylphosphonamide monoethyl
esters 1, leading to the formation of the phosphaisoquinolin-1-ones 2 (Scheme 1).
The current reaction shows very high regioselectivity to give 6-endo-dig cyclization product. In
each case, only the six-membered endocyclic phosphaisoquinolin-1-ones were obtained, To probe
whether the synthesized phosphaisoquinolin-1-ones possessed biological activities, their in vitro
anti-tumor properties were evaluated in an A-549 lung cell line by the SRB assay. At a
concentration of 10-4 mol/L, the A-549 lung cell growth inhibition ratios of 2a, 2c, 2d, 2e, 2f, 2h,
2j, 2l are 97.2%, 74.7%, 83.2%, 97.0%, 97.2%, 97.2%, 97.5%, 97.2%, respectively; but their
biological activities drop obviously with the decrease of concentration. We capture some
unexpected intermediates 4, 5, 6 (Scheme 2) by ESI-MS,3 CSI-MS4 technic, which could leads to a
deep understanding of the mechanism of the palladium-catalyzed cyclization.
153

Recfereces:
(1) Dillon, K. B.; Mathey, F.; Nixon FRS, J. F. Phosphorus: The Carbon Copy; John Wiley & Sons: Chichester, 1998.
(2) Alonso, Francisco, Beletskaya, Irina P., Yus, Miguel., Chem.Rev. 2004, 104, 3079-3159.
(3) a) L. S. Santos, J. O. Metzger, Angew. Chem. Int. Ed. 2006, 45, 977-981; d) C. Trage, D. Schröder, H. Schwarz;
Chem. Eur. J. 2005, 11, 619 – 627; m) H. Guo, R. Qian, Y. Liao, S. Ma, and Y. Guo, J. Am. Chem. Soc. 2005, 127,
13060-13064.
(4) a) L. Pazderski, E. Szłyk, J. Sitkowski, B. Kamienski, L. Kozerski, J. Tousek, R. Marek Magn. Reson. Chem. 2006;
44: 163–170; b) E. Szłyk, A. Grodzicki, L. Pazderski, A. Wojtczak, J. Chatłas, G. Wrzeszcz, J.Sitkowski, B. Kamienski,
J. Chem. Soc., Dalton Trans., 2000, 867–872.
154

P-174
NOVEL PYRIDO- AND BENZO-ANNULATED 1,3-AZAPHOSPHOLES
J. Heinicke, a M. S. S. Adam, a B. R. Aluri, a P.G. Jones b
EMA-University Greifswalda (Germany), Technical University Braunschweigb (Germany)
Benzazaphospholes are particularly stable π-excess aromatic heterophospholes [1], suitable for
the study of donor-substituted derivatives for use as hybrid ligands and in catalysis. Syntheses of
novel pyrido- and benzo-annulated 1,3-azaphospholes, comprising Pd-catalyzed C-N and C-P
couplings, reduction and ring closure, are presented (e.g. Scheme). Ni-catalyzed P-C coupling and
reductive cyclization, applicable for 1H-1,3-benzazaphospholes, fail for pyridine- or N-tertiary
derivatives. Tolerance or restrictions by other functions will be reported.
X
1. LiAlH 4
2. Me 2NCH(OMe) 2
X = CH, N
Pd catalyst
Br
+ RNH2 Br
X
P
N
R
X
Br
NH
R
1. tBuLi
2. Electrophile
155
Pd catalyst
HPO(OEt) 2 / base
or P(OEt) 3
X
X
P
N
R
EtO OEt
or addition product depending on
substituents and conditions
A first oxidation-dimerization product of a benzazaphosphole (center), trapped by
cocrystallization with the respective benzazaphosphole (left and right) in a supra-molecular,
hydrogen-bonded arrangement, has been characterized by X-ray structure analysis.
Reference
[1] R. K. Bansal, J. Heinicke, Chem. Rev. 2001, 101, 3549-3578.
.
P
N
R
E
O
H

P-177
DESIGNING PHOSPHORUS LIGANDS AT THE P-CENTER FOR ASYMMETRIC
REACTIONS CATALYZED BY Rh or Pd COMPLEXES
C. Darcel,* a D. Moulin, b C. Bauduin, b M. Gomès, a J.C. Henry, d M. Lagrelette, a P. Richard, a
P.D. Harvey c and S. Jugé* a
[a] Institut de Chimie Moléculaire de l'Université de Bourgogne,UMR CNRS 5620, 9 av. A. Savary, 21078
Dijon, France; e-mail: Christophe.Darcel@u-bourgogne.fr, Sylvain.Juge@u-bourgogne.fr
[b] BASF-Aktiengesellschaft; GCI/B-M 311, 67056 Ludwigshafen, Germany.
[c] Département de Chimie de l'Université de Sherbrooke, Sherbrooke J1K2R1 Québec, Canada,
[d] SYNTHELOR SAS- 102 impasse H. Becquerel, Dynapôle de Ludres-Fléville 54510 Ludres, France
Introducing the chirality on the phosphorus atom of a ligand is of particular interest to handle the
chiral environment of the catalyst center. Herein we report the diastereoselective synthesis of new
P-chirogenic phosphorus ligands, AMPP 1, phosphine-phosphinites 2 and ferrocenyl aminophosphine
3, and their applications in hydrogenation and allylic alkylation catalyzed by rhodium or palladium
complexes, respectively. The enantioselectivity of the catalyzed reaction was considered to the light
of ligands and complexes structures.
R
CH3 1
Ph
P
N
CH 3
P
O
Ph
R 2
R 3
1
R 1
R 2
P
156
P
O
R 3
R 4
2
Fe
NR 2
P
R1 R2 3
Our results showed that changing properly the R 1 -R 3 groups of the AMPP 1 thanks to the
P-chirogenic chlorophosphine building blocks, 1 leads to hydrogenated compounds in e.e. from 99% (S)
to 80% (R). 2 In addition, we have shown that the chirality beared by the phosphine part of the ligand 2,
is essential for the asymmetric induction. Finally, in the case of the ferrocenyl aminophosphine 3, the
phosphorus or the planar chirality are stereodeterminant, in catalyzed hydrogenation and allylation,
respectively.
Me
Ph
R 3
R
R
H2 substrate
1
Me
N
O P
Rh
COD
R 2
MeO 2C NH
These results leads us to propose models in order to explain the enantioselectivity of the catalysis.
Reference
1) C. Bauduin, D. Moulin, El B. Kaloun, C. Darcel, S. Jugé J. Org. Chem. 2003, 68, 4293.
2) C. Darcel, D. Moulin J.C. Henry, M. Lagrelette, P. Richard, P. D. Harvey, S. Jugé, Eur. J. Org. Chem. 2007 in press.
O
Rh H
H
Ph
CH 3
MeO 2C NHCOMe
(S)
Ph

P-196
N-HETEROCYCLIC CARBENE-COPPER COMPLEX-CATALYZED
HYDROPHOSPHINYLATION OF ALKYNES
Mingyu Niu, Hua Fu,* Yuyang Jiang and Yufen Zhao
Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology, Ministry of Education, Department of
Chemistry, Tsinghua University, Beijing 100084, P. R. China.
Fax: 86-10-62781695; Tel: 86-10-62797186; E-mail: fuhua@mail.tsinghua.edu.cn
N-Heterocyclic carbenes (NHCs) have emerged as a new class of ligand for homogeneous
catalysis in the past decade. 1 Since Arduengo reported the first (NHC)-copper complex derived
from imidazolium salt and copper triflate, 2 the NHC-copper complexes have been reported to
catalyze a number of reactions. Hydrophosphinylation of alkynes is one of the most straightforward
ways for the preparation of alkenylphosphine oxides, Several efficient methods for metal-catalyzed
synthesis of alkenylphosphine oxides have been developed including palladium, 3 nickel, 4 rhodium, 5
ytterbium-imine complex-catalyzed 6 additions of P(O)H compounds to alkynes. Recently, we have
developed efficient copper-catalyzed additions of P(O)H compounds to alkynes, and the reactions
provided the regio- and stereoselective E-alkenylphosphine oxides under catalysis of the
commercially available and inexpensive copper catalyst system CuI/ethylenediamine. 7 Herein, we
report a new method for synthesis of alkenylphosphine oxides using the NHC-copper complex as
the catalyst.
R 1
+
H
Cat. =
O R 2
P
R 3
157
5mol % Cat.
N N
References:
(1) For reviews, see: (a) D. Bourissou, O. Guerret, F. P. Gabbai, G. Bertrand, Chem. Rev. 2000, 100, 39. (b) W. A.
Herrmann, Angew. Chem.,Int. Ed. 2002, 41, 1290.
(2) A. J. Arduengo, ,III, H. V. R. Dias, J. C. Calabrese, F. Davidson, Organometallics. 1993, 12, 3405.
(3) (a) L.-B. Han, R. Hua , M. Tanaka, Angew. Chem., Int. Ed. 1998, 37, 94; (b) A. Jr. Allen, L. Ma, W. Lin,
Tetrahedron Lett.2002, 43, 3707.
(4) L.-B. Han, C. Zhang, H. Yazawa, S. Shimada, J. Am. Chem. Soc. 2004, 126, 5080.
(5) L.-B. Han, C.-Q. Zhao, M. Tanaka, J. Org. Chem. 2001, 66, 5929.
(6) K. Takaki, M. Takeda, G. Koshoji, T. Shishido, K. Takehira, Tetrahedron Lett. 2001, 42, 6357.
(7) M. Y. Niu, H. Fu, Y. Y. Jiang, Y. F. Zhao, Chem. Commun. 2007, 3, 272.
CuCl
R 1
P
O
R 2
R 3

Symposium 3
Structure and Reactivity of Inorganic
Phosphorus Compounds

KL-11
BIOLOGICALLY RELEVANT PHOSPHORANES: STRUCTURAL
CHARACTERIZATION OF GLUCOFURANOSE AND XYLOFURANOSE
PHOSPHORANES AS APPLIED TO PHOSPHORYL TRANSFER ENZYMES
Robert Holmes* A. Chandrasekaran, and Natalya V. Timosheva
Department of Chemistry, University of Massacusetts, USA Email: rrh@chem.umass.edu
Factors Influencing Donor Coordination Leading to Hypervalency
The coordination tendencies of phosphorus to form a hexacoordinated state from a
pentacoordinated state, which might assist in describing the mechanistic action of phosphoryl
transfer enzymes, are delineated. The factors discussed include substrate and transition or
intermediate state anionicity, hydrogen bonding, packing effects, that is, van der Waals forces, the
ease of formation of hexacoordinate phosphorus from lower coordinate states, and the
pseudorotation problem common to nonrigid pentacoordinate phosphorus. In view of the work
reported here and recent work on enzyme promiscuity and moonlighting activities, it is suggested
that donor action should play a role in determining active site interactions in phosphoryl transfer
enzyme mechanisms.
Ease of Formation of the Hexacoordinate State
Biochemists studying phosphoryl transfer enzymes outline mechanisms of nucleophilic attack at
phosphorus that take place by way of proposed trigonal bipyramidal intermediates or transition
states. However, recent work has shown the ready availability of higher coordinate forms of
phosphorus, particularly the ease of formation of hexacoordinate phosphorus. Recently we reported
the unprecedented ease of conversion of tricoordinate to hexacoordinate phosphorus with typical
donor atoms found at the active sites of enzymatic reactions. In solution, the existence of these two
disparate geometries are found in equilibrium with one another.
Biochemical Implications
In the area of promiscuous phosphoryl transfer enzymes, the present work provides a mechanism
for such enzymes to conduct different reactions at the same active site. For example, the active site
of chymotrypsin is able to catalyze both amidase and phophotriesterase reactions. Our recent
publications established the X-ray structure of several biorelevant phosphoranes. Included are the
structures that were established of one xylofuranose based phosphorane 1 and one thymidine based
phosphorane 2.
O O
O
P
F
O
(1A)
O
O
O
159
Solution
Solid
O O
O
O
P O
F
(1B)
O
O

O
O
O
P
F
O
O
H
N O
O N
Solution
Solid
160
F
O
O P
O
(2A) (2B)
O
O N
O N
H
O
In solution, the bicyclic phosphorane 1 showed dynamic equilibrium between two isomeric forms
while phosphorane 2 showed a static conversion between two isomers, one in solid state and the
other in solution state. In addition, bicyclic phosphorane 3 exists in equilibrium between
pentacoordinated and hexacoordinated isomeric forms.
O
OCH2CF3 O
S O P O
O
3
The rapid exchange process between these two geometries reorients the nucleotidyl or
carbohydrate component of the trigonal bipyramidal phosphorane. At an active site, this type of
pseudorotational behavior provides a mechanism that could bring another active site residue into
play and account for a means for phosphoryl transfer enzymes to express promiscuous behavior.
Pseudorotation, a well-founded process in non-enzymatic phosphorus chemistry may have an
application in the future of phosphoryl transfer enzyme chemistry.
Pertinent References
1. N. V. Timosheva, A. Chandrasekaran, and R. R. Holmes, ” Biologically Relevant Phosphoranes: Synthesis and
Structural Characterization of Glucofuranose Derived Phosphoranes with Penta and Hexacoordination at Phosphorus, ”
Inorg. Chem., 46, 0000-0000 (2007).
2. N. V. Timosheva, A. Chandrasekaran, and R. R. Holmes, “Biologically Relevant Phosphoranes: Structural
Characterization of Glucofuranose and Xylofuranose Based Phosphoranes,” Inorg. Chem., 45, 3113-3123 (2006).
3. N. V. Timosheva, A. Chandrasekaran, and R. R. Holmes, “Biologically Relevant Phosphoranes: Structural
Characterization of a Nucleotidyl Phosphorane,” J. Am. Chem. Soc., 127(36), 12474-12475 (2005).
4. R. R. Holmes “Phosphoryl Transfer Enzymes and Hypervalent Phosphorus Chemistry,” Acc. Chem. Res., 37,
746-753 (2004).
5. N. V. Timosheva, A. Chandrasekaran, R. O. Day, and R. R. Holmes, “Conversion of Tricoordinate to Hexacoordinate
Phosphorus. Formation of a Phosphorane-Phosphatrane System,” J. Am. Chem. Soc., 124, 7035-7040 (2002).
HO
O
O
O
O

KL-19
STUDIES ON STABLE 1,3-DIPHOSPHACYCLOBUTANE-2,4-DIYLS
Masaaki Yoshifuji,a Anthony J. Arduengo, III a and Shigekazu Itob
a Department of Chemistry, The University of Alabama, Tuscaloosa, AL 35487, USA
b Department of Chemistry, Graduate School of Science, Tohoku University,Aoba, Sendai 980-8578, Japan
A sterically protected phosphaalkyne 1 reacted with 0.5 eq of t-butyllithium to give a
4-membered ring phosphide anion, 3, via intermediate 2. When 3 was quenched with methanol as
a proton source [1], 1,4-diphosphacyclobutene 4 [2] was obtained and the structure was analyzed by
X-ray crystallography. Oxidation of 3 with 0.5 eq of iodine resulted in the formation of a neutral
radical 5 (pink). Radical 5 was a stable crystalline compound and its structure was analyzed by
X-ray diffraction and EPR spectroscopy [3].
Mes* C P
1
tBuLi
Mes*= 2,4,6-tBu 3C 6H 2
Mes* C P tBu
1
Mes*
tBu
P
Mes*
2
P
3
Mes*
H
tBu
P
Mes*
P
4
MeOH
161
tBu
P
Mes* Mes*
P
5
MeI
tBu
tBu
Mes*
P
P
Mes*
(4-BrC 6H4) 3N
Mes*
P
P
Mes*
Me 7
Me 6
+• – •SbCl6 When the phosphide 3 was quenched with methyl iodide, a stable biradical species
X
6 (dark blue) was obtained [4]. The structure of 6 was determined by X-ray analysis
P
indicating that two Mes* groups protect efficiently two carbon radical centers.
P
Compound 6, 1,2-diphosphacyclobutane-2,4-diyl, is a member of a new class of
Y
8
stable biradicals, on which Niecke [5] and Bertrand [6] have recently reported.
Changing the identities of the nucleophile (from t-BuLi) and the electrophile (from MeI), various
derivatized biradicals 8 (X, Y= Me, Et, PhCH2, n-Bu, t-Bu, n-C18H37, n-C3F7, PhC(O), and i-Pr2N)
were formed [7,8,9]. Several of these biradicals were characterized by X-ray crystallography.
NMR, UV, and CV data for 8 will also be discussed. Furthermore, 6 reacted with
tris(4-bromophenyl)ammoniumyl hexachloroantimonate as an oxidant to give the corresponding
cation radical 7 [10] and the structure was determined by analysis of its EPR spectrum.
References
[1]A. M. Arif, A. R. Barron, A. H. Cowley, S. W. Hall, J. Chem. Soc., Chem. Commun. 1988, 171.
[2]S. Ito, H. Sugiyama, M. Yoshifuji, Chem. Commun. 2002, 1744. [3]S. Ito, M. Kikuchi, M. Yoshifuji, A. J. Arduengo,
III, T. A. Konovalova,, L. D. Kispert, Angew. Chem. Int. Ed. 2006, 45, 4341. [4]H. Sugiyama, S. Ito, M. Yoshifuji,
Angew. Chem. Int. Ed. 2003, 42, 3802. [5]E. Niecke, A. Fuchs, F. Baumeister, M. Nieger, W. W. Schoeller, Angew.
Chem., Int. Ed. Engl. 1995, 34, 555.[6]D. Scheschkewitz, H. Amii, G. Gornitzka, W. W. Schoeller, D. Bourissou, G.
Bertrand, Science 2002, 295, 1880.[7]H. Sugiyama, S. Ito, M. Yoshifuji, Chem. Eur. J. 2004, 10, 2700.[8]M. Yoshifuji,
H. Sugiyama, S. Ito, J. Organomet. Chem. 2005, 690, 2515.[9]S. Ito, M. Kikuchi, H. Sugiyama, M. Yoshifuji, J.
Organomet. Chem. in press, DOI: 10.1016/j.jorganchem.2006.10.066.[10]M. Yoshifuji, A. J. Arduengo, III, T. A.
Konovalova, L. D. Kispert, M. Kikuchi, S. Ito, Chem. Lett. 2006, 45, 4341.
I 2
Mes* Mes*

IL-31
ORGANOPHOSPHORUS Pi-CONJUGATED MATERIALS FOR
OPTOELECTRONIC APPLICATIONS
Muriel Hissler, Christophe Lescop, Régis Réau*
Phosphore et Matériaux Moléculaires, Université de Rennes 1, UMR CNRS 6226,
Campus de Beaulieu, F-35042, Rennes, France Email: regis.reau@univ-rennes1.fr
Organophosphorus building blocks have been rarely used for the tailoring of π-conjugated
systems. 1 In our group, we have exploited the unique properties of the phosphole ring (low aromatic
character, σ,π-conjugation) to develop a novel family of π-conjugated oligomers and polymers. Of
particular interest, the P-atom of phospholes exhibits a versatile reactivity allowing direct access to
a range of new -conjugated systems including transition metal complexes. 2,3 These chemical
modifications of the P-atom offer a way to diversify their electronic and optical properties and are
key issues for the optimization of phosphole-based materials toward optoelectronic applications. For
example, access to organophosphorus-containing OLED materials will be presented. 4 The synthesis
of the first phosphole-modified polythiophene will be reported. 5 Due to the presence of reactive
P-atom, this conjugated polymers (CPs) can sense chalcogenides, an unprecedented property for
CPs. Lastly, using the ability of phospholes to coordinate metal centers, 3 we have design
Cu(I)-dimmers which are molecular clips for the synthesis of nano-scale supramolecular assemblies
having a [2.2]-paracyclophane topology. [6] The scope of this method to control the organisation of
classic π-conjugated systems in the solid state will be presented.
References
[1] T. Baumgartner, R. Réau, Chem. Rev. 2006, 106, 4681..
[2] J. Casado, R. Réau, J. T. López Navarrete, Chem. Eur. J., 2006, 12, 3759
[3] F. Leca, C. Lescop, E. Rodriguez, K. Costuas, J.-F. Halet, R. Réau Angew. Chem. Int. Ed., 2005, 44, 2190.
[4] H.-C. Su, O. Fadhel, C.-J. Yang, T.-Y. Cho, C. Fave, M. Hissler, C.-C. Wu, R. Réau J. Am. Chem. Soc., 2006, 128,
983.
[5] M. Sebastian, M. Hissler, C. Fave, J. Rault- Berthelot, C. Odin, R. Réau, Angew. Chem. Int. Ed., 2006, 45, 6152.
[6] B. Nohra, S. Graule, C. Lescop, R. Réau, J. Am. Chem. Soc., 2006, 128, 3520.
162

IL-32
RECENT ADVANCES IN THE CHEMISTRY OF P,N-HETEROCYCLES
Streubel*, R., Özbolat, A., Helten, H., Perez, J. M., and Nieger M.
Institut für Anorganische Chemie, Gerhard-Domagk-Str. 1, D-53121 Bonn;
E-mail: r.streubel@uni-bonn.de
Gaining mild access to small- and medium-sized heterocycles and to use them as starting
materials for new and selective transformations are current synthetic challenges in phosphorus
chemistry. 2H-Azaphosphirene complexes might serve as a good case-in-point, e.g., we have shown
that they are well suited for thermal, photochemical and even catalytical reactions. [1] Here we report
on the use of 2H-azaphosphirene complexes I in the synthesis of 1,3,2-oxaza-phosphole-3-ene
II, [2] 1,3,4-oxazaphosphol-2-ene II, [3] 1,3,5-oxaza-phosphole-4-ene IV, [4] 1,2H-azaphosphole-5-ene
V, [5] 2H-1,4,2-diazaphosphole complexes VI [6] and 3H-1,3-azaphosphole complexes VII [7]
(Scheme). A new access to I will be reported, too. [8]
(OC) 5W
(OC) 5W
R
R
R
R
R
R 1
P
O N
R
I-VII: R 1 = CH(SiMe 3) 2
I, IV, VI, VII: R 2 = Ph, NMe 2
I-VII: R = alkyl, aryl
R
P
R 1
N
R
II
(OC) 5W
R
R
(OC) 5W R 1
R 2
(OC) 5W
O
P
P
C N
N
163
R 1
N
R 1
R
I
III
(OC) 5W
P
R
N
2
P
R2 R
V VI VII
R
R 2
(OC) 5W
NMR data, X-ray structures and DFT studies on various reaction courses using model systems
will be presented and discussed.
Reference
[1] Review: R. Streubel, Coord. Chem. Rev. 2002, 227, 175.
[2] a) U. Rohde, F. Ruthe, P. G. Jones, R. Streubel, Angew. Chem. Int. Ed. 1999, 38, 215; b) R. Streubel, P. G. Jones, R.
Streubel, unpublished.
[3] a) H. Wilkens, F. Ruthe, P. G. Jones, R. Streubel, Chem. Eur. J. 1998, 4, 1542; b) N. Hoffmann, R. Streubel, L.
Ricard, N. Hoa Tran Huy, F. Mathey, C. R. Chimie 2004, 7, 927.
[4] a) C. Neumann, A. Prehn Junquera, C. Wismach, P.G. Jones, R. Streubel, Tetrahedron 2003, 59, 6213; b) R.
Streubel, J. M. Perez, M. Nieger, unpublished.
[5] a) N. Hoffmann, P. G. Jones, R. Streubel, Angew. Chem. Int. Ed. 2002, 41, 1226; b) R. Streubel, H. Wilkens, F.
Ruthe, P. G. Jones, Organometallics 2006, 25, 4830.
[6] H. Helten, M. Nieger, G. Schnakenburg, R. Streubel, submitted.
[7] H. Helten, R. Streubel, unpublished.
[8] A. Özbolat, G. von Frantzius, M. Nieger, R. Streubel, submitted.
N
N
P
R
R 1
O
R 1
R
R
IV

IL-50
RADIATION-INDUCED SYNTHESIS OF POLYMERS ON THE BASIS OF
ELEMENTAL PHOSPHORUS
N.P. Tarasova
D.Mendeleyev University of Chemical Technology of Russia
Miusskay Sq., 9, Moscow, 125047 Russia, E-mail tarasnp@muctr.edu.ru
The wide use of red phosphorus in different branches of the industry: the defense, the synthesis
of materials for electronics, nonferrous metallurgy, production of the flame retardants for polymeric
materials, organophosphorus synthesis, – specifies the search for the simple and easily controlled
processes of the synthesis of the polymers of element phosphorus with the useful properties.
We have carried out the studies of the radiation-induced synthesis of the polymers based on the
elemental phosphorus. The use of methods of radiation chemistry made it possible to solve a
number of problems, traditional in the synthesis of the red phosphorus:
1. The reduction of the temperature of the beginning of the reaction of the formation of red
phosphorus from the white one and the enlargement of the temperature interval of the process.
2. The variation of the conditions of the initiation of the reaction by the ionizing radiation makes it
possible to govern the composition and the structure of phosphorous-containing polymer;
3. The methods of the synthesis of high molecular mass compounds (bulk polymerization,
polymerization in the solution and emulsion polymerization) being applied to the inorganic
monomer –the white phosphorus, has made it possible to obtain phosphorus-based polymers with
different structures. The basic factors, which control the properties of end product, have been
investigated, depending on the method of the synthesis used. It possible to obtain:
• using the radiation-induced balk polymerization - the analogs of thermal red phosphorus
with the low degree of polymerization, the red phosphorus with the desirable radiation, thermal
and doped defectiveness;
• using the polymerization in solution-phosphorous-containing polymers with the low degree
of polymerization. The polymeric products contain the fragments of the solvents (RO, C6H5, CCl3,
C2H5O, etc.). The reactivity of the synthesized polymers is comparable with that of the white
phosphorus;
• using the polymerization of white phosphorus in the dispersed state (water emulsions)phosphorous-based
polymers in the shell-growth process. It is possible to regulate the size of
polymeric particles, porosity, and reaction ability of the polymer.
The qualitative and quantitative characteristics of the process and of the end products obtained
will be discussed.
164

O-72
INFLUENCE OF MEDIA COMPONENTS ON PROCESSES OF RADIATION-INDUSED
POLYMERIZATION OF WHITE PHOSPHORUS
I.M. Artemkina, A.S. Vilesov, Y.V. Smetannikov, N.P. Tarasova
D. Mendeleyev University of Chemical Technology of Russia, Miusskaya sq. 9, Moscow, 125047, Russia.
E-mail: tarasnp@muctr.edu.ru, vilesov@gmail.com
It is known that inorganic polymers (such as red phosphorus, polymeric forms of arsenic, sulfur,
and their compositions) recently become the objects of intensive both theoretical and applied
investigations, since determination of fundamental characteristics shows the researchers optimal
ways for synthesis of such polymers. It also will be useful for the solution of the general problem
“architecture” of a molecule – structure of inorganic material – their physicochemical properties”.
Nowadays the development of green technologies is one of priority directions both for science and
for the industry. Red phosphorus, being one of the well-known allotropic modifications of
elemental phosphorus, is now being defined as a three-dimensional inorganic polymer with
homo-chains P-P. It is known that the reaction conditions, the properties of the solvent, additives,
etc., may lead to drastic changes in the rate of polymorphic transformation. The evidence exists
confirming the fact that the polymerization of white phosphorus might be initiated by intermediates
of different nature.
The object of our research is the radiation-induced polymerization of white phosphorus in the
presence of ionic liquids (IL) to give red phosphorus. It is a worthy alternative to the conventional
procedure of high-temperature transformation of the white phosphorus to the red one. As we have
shown in our previous studies, the mechanism of the radiation-induced polymerization of white
phosphorus in non-polar solvents (benzene, halohydrocarbons, hexane) is the radical one.
One might expect, by rising the reaction media polarity, to increase the role of the ionic
contribution to the formation of the phosphorus-containing polymers (PCP). IL are the powerful
instrument for the “tuning” of reaction system properties. It was this capacity that we have used for
the intensification of the radiation-induced polymerization process of white phosphorus.
The presence of IL ( 1-ethyl-3-methylimidazolium bis(trifluoromethane-sulfonyl)imide,
1-butyl-3-methylimidazolium trifluoromethanesulfonate, 1-butyl-1-metylpyrro-lidinium
bis(trifluoromethylsulfonyl)imide , 1-butyl-3-methylimidazolium tetrafluoro-borate ,
1-butyl-3-methylimidazolium hexafluorophosphate, 1-hexyl-3-methylimidazolium
tris(penta-fluoroethyl)trifluorophosphate) – compounds with charge separation systems – in the
reaction media (P4–DMSO, P4–benzene–DMSO) led to the full conversion of white phosphorus to
be achieved at absorbed doses of about 20 kGy.
The observed acceleration of the polymerization rate of phosphorus in the presence of ionic
liquids is supposed to be the result of the formation of the intermediate complex [P4-IL]. The NMR
P 31 data confirmed the hypothesis of the complex formation.
Therefore, we were first to show that in the conditions of the radiation-induced polymerization of
white phosphorus in solution formation rate of phosphorus-containing polymers could be increased
by taking control of media polarity.
165

O-73
AN EFFECTIVE METHODOLOGY OF P,N-MACROCYCLES DESIGN
A.A. Karasik a , A.S. Balueva a , R.N. Naumov a , D.V.Kulikov a , Yu.S.Spiridonova a , O.G.Sinyashin a , E. Hey-Hawkins b .
a
A. E. Arbuzov Institute of Organic and Physical Chemistry, Russian Academy of Sciences, Arbuzov str. 8, Kazan,
Russia, 420088. E-mail: oleg@iopc.knc.ru
b
Institut für Anorganische Chemie der Universität Leipzig, Johannisallee 29, D-04103 Leipzig, Germany. E-mail:
hey@rz.uni-leipzig.de
High effective covalent self-assembly of the macrocyclic polyphosphines has been found in the
course of investigation of Mannich type condensation in the system: phosphine, formaldehyde and
amine if bifunctional reagents (spatially divided diamines 1 or di(arylphosphino)alkanes 2 ) had been
used. A number of 16-, 28-, 36- and 38-membered cyclic aminomethylphosphines and cage
macrocycles with large hydrophobic intramolecular cavities have been obtained.
Ar
P
Ar'
Ar
N
R
P
P
R
N
Ar
Ar'
P
Ar
Ar Ar
P P
or ArPH2 H H
Me
N
Me
P
N
N Me
Ar
P N
Me
Ar
X
R
R
O
O
P
P
N
N
R
N
N
N
N
R
P
P
R
P
P
R
P
P
O
O
166
R
R
Ph
N
Ar
P
P
Ar
N
N
Ph
P
P
Me
N
Me
O
NMe
O
Me
Me
Me
Me
Me
Me
O
NMe
O
N
P
P
Ph
+ CH2O + ArCHRNH 2 or H 2N NH 2 or HRN NRH
So, the formation of covalent macrocycles appears to be a general process and may be considered
as a useful method for a simple one-pot synthesis of macroheterocyclic polyphosphines.
Financial support from Volkswagen Foundation, RFBR (No. 06-03-32754-a), Russian Science
Support Foundation and from President’s of RF Grant for the support of leading scientific schools
(No. 5148.2006.3) is gratefully acknowledged.
Reference
1. A.S. Balueva et al Dalton Trans. 2004, 442;
2. A.A. Karasik et al Heteroat. Chem. 2006, 499;
3. A.A. Karasik et al Z.Anorg Allg.Chem. 2007;
4. R.N. Naumov et al Dalton Trans 2004, 357.
N
N
X
N
P
N
Ar
P
N
Ar
Ph

O-74
THE MECHANISM OF THE REACTION OF ALKALI METAL PHENOXIDES WITH
HEXAHALOCYCLOTRIPHOSPHAZENES
Christopher W. Allen, Michael Calichman and Amy Freund,
Department of Chemistry, University of Vermont, Burlington, VT, 05405, USA
The study of reactions at the phosphorus (V) center in the cyclotriphosphazenes allows for a
fundamental understanding of the factors controlling reactivity in phosphorus chemistry. Previous
kinetic and mechanistic investigations of the nucleophilic substitution reactions of
hexahalocyclotriphosphazenes have almost exclusively been devoted to systems where the
nucleophile is an amine. The phenoxy substituent is one of the most ubiquitous in cyclo- and
polyphosphazene chemistry so in order to gain a more general picture of the factors controlling the
reactivity of the phosphazenes, we have examined the kinetics of the reactions of N3P3X6 (X=F,Cl)
with the alkali phenoxides, MOPh ( M=Li,Na,K). DFT calculations using the SCI-PCB model
show that in terms of enthalpic contributions the associative mechanism is favored. Experimental
kinetic studies were carried out using GC-mass spectrometry and 31 P NMR spectroscopy.
Contrary to conventional wisdom, the rate of the reaction of the fluorophosphazene is much faster
than that of the chlorophosphazene. In the reactions of N3P3Cl6-nFn (n=2, 4) substitution occurs
exclusively at the PF2 centers and the liberated fluoride ion acts as a nucleophile towards the PCl2
center. These observations are consistent with our calculated NBO charges at the relative
phosphorus centers. The variations of the rate of reaction with temperature, solvent and alkali
metal cation have been determined. The activation parameters for the chlorophosphazene system
show positive enthalpy and entropy of activation. This is in contrast to systems involving amines
as nucleophiles where negative entropies of activation have been determined. The reaction rates
of the chlorophosphazene increase with solvent basicity. The rates of reaction for the heavier
alkali metal cations are greater than those for the lighter cations. This trend is the reverse of the
trend in the metal salt lattice energies thus formation of the alkali metal salt is not part of the rate
determining step. The addition of crown ethers results in a significant rate increase. Consideration
of all of these data suggest a mechanism where the rate has a major contribution from a
preequilibrium wherein the metal phenoxide cluster dissociates into the kinetically active species
which adds, in the rate determining step, to the Phosphorus (V) center i.e. the transition state is
before the intermediate. This is in contrast to the amine systems wherein the rate determining
step is the formation of the hydrohalide and thus the transition state occurs after the intermediate.
167

O-75
STRAINED P2C AND P2C2 CYCLIC CATIONS FROM PHOSPHAALKENES
Derek P. Gates
Department of Chemistry, University of British Columbia, Vancouver, British Columbia, CANADA, V6T 1Z1
dgates@chem.ubc.ca
Highly strained phosphorus heterocycles are attractive synthetic targets due to their novel
structures, bonding, and their utility as building blocks in organophosphorus chemistry. 1
Moreover, phosphorus heterocycles often have no isolable counterparts in nitrogen chemistry, and
consequently, they provide unique insight into the striking differences between the chemistry of the
first and second periods. A dramatic illustration of this difference is provided by the pioneering
investigations of the (P2CR5) + cation which is isolated as the symmetric diphosphiranium (A) rather
than the open-chain form (B). 2 In contrast, (N2CR5) + adopts the open chain form B. We have been
interested in the elusive asymmetric diphosphiranium (C) which is formally a valence isomer of the
acyclic 3-phosphino-1-phosphenium ion (D).
P
C
P
+
P P
C
+
168
P
C
P
+
P P
C
A B C D
An asymmetric diphosphiranium cation has previously been detected spectroscopically in
solution. 3,4 In this presentation, a simple route to isolable diphosphiranium cations of type C will
be disclosed. 5 In particular, treating phosphaalkene 1 with HOTf (0.5 equiv) affords asymmetric
diphosphiranium 2[OTf] which can be isolated and characterized by X-ray crystallography.
Surprisingly, the analogous reaction of 1 with MeOTf (0.5 equiv) affords 1,3-diphosphetanium
3[OTf] where the methyl group from MeOTf is found at phosphorus rather than carbon. The
detection of intermediates in these reactions and the unusual umpolung-like reactivity for the P=C
bond in 1 will also be discussed. In addition, the generality of these new reactions and the possible
use of these novel rings as precursors to new polymers will also be considered in this presentation.
1
2 3
References
1. Mathey, F., Phosphorus-Carbon Heterocyclic Chemistry: The Rise of a New Domain. Pergamon: Amsterdam,
2001.
2. See: (a) Kato, T.; Gornitzka, H.; Baceiredo, A.; Schoeller, W. W.; Bertrand, G. Science 2000, 289, 754; (b) Kato,
T.; Gornitzka, H.; Baceiredo, A.; Schoeller, W. W.; Bertrand, G. J. Am. Chem. Soc. 2002, 124, 2506.
3. Loss, S.; Widauer, C.; Rüegger, H.; Fleischer, U.; Marchand, C. M.; Grützmacher, H.; Frenking, G. Dalton Trans.
2003, 85.
4. Tsang, C.-W.; Rohrick, C. A.; Saini, T. S.; Patrick, B. O.; Gates, D. P. Organometallics 2004, 23, 5913.
5. Bates, J. I.; Gates, D. P. J. Am. Chem. Soc. 2006, In Press.
+

O-76
NEW REAGENTS FOR HALOGENATION OF PHOSPHORUS
Rikard Wärme and Lars Juhlin
Swedish Defence Research Agency NBC defence
Cementvägen 20, 901 82 UMEÅ, SWEDEN. e-mail: rikard.warme@foi.se
Syntheses of phosphorus halides are of interest in many genres of organic chemistry but the
development of new methods and reagents for their synthesis have been scarcely explored. Working
in small scale put extra demands on reactions as well as purification procedures to ensure that losses
can be kept at a minimum. New reagents for these reactions which have properties like fast and
clean reactions on micro scale with minimum work up procedures will be presented.
The versatility of the reagents is further explored by the synthesis and use of solid supported
reagents. The reagents are mild and compatible with many functional groups and selective towards
phosphorus which enables the reactions to be used in a variety of systems. Clean reactions and easy
work-up procedures ensures excellent yields which, only with a few exceptions, are quantitative.
These reagents have proven suitable for micro scale synthesis especially in the solid phase
application.
169

O-79
BIMETALLIC ACTIVATION OF WHITE PHOSPHORUS
Dmitry Yakhvarov, a Maurizio Peruzzini, b Maria Caporali, b Pierluigi Barbaro, b Luca Gonsalvi, b Stefano Midollini, b
Annabella Orlandini, b Fabrizio Zanobini, b Yulia Ganushevich a and Oleg Sinyashin a
a
A.E. Arbuzov Institute of Organic and Physical Chemistry, 420088 Kazan (Russia)
b
ICCOM CNR, 50019 Sesto Fiorentino (Italy)
e-mail: yakhvar@iopc.knc.ru
The reactivity of white phosphorus with transition metals is characterized by a vast diversity of
bonding conditions and structural motifs resulting in a variety of Px units ranging from single
phosphido atoms to high nuclearity polyphosphorus ligands. 1 When the tetraphosphorus array is
preserved, different topologies are observed containing either the intact P4 molecule, behaving as a
monohapto 2 or dihapto ligand, 3 or activated by opening one or more edges, generating acyclic P4
chains. 1 These find their thermodynamic sinks by either bridging two metal moieties 4 or undergoing
electrophilic or nucleophilic attacks by ancillary ligands to form new P-H, P-C and P-P bonds, 5 as
for the unique cobalt complex [Co(Ph2PCH2PPh2PPPPPh2PCH2PPh2)]BF4 prepared more than two
decades ago. 6 The mechanism of formation of the Co(I)-coordinated 1,2-disubstituted
tetraphosphabutadiene zig-zag P6 chain has not been clearly understood as yet. Herein we describe
the syntheses, characterizations and reactivity of new rhodium and iridium species related to this
intriguing activation process and highlight the occurrence of an unexpected bimetallic P4 activation
pathway to mediate the whole reaction. 7
2
P P
M
P P
M = Rh, Ir
+
P
P
P
P
CH2Cl2 - 40 °C
P
P
P
M
P
P
P
P
P
P
M
P
P
P
170
2+
- [M(dppm) 2] +
Acknowledgements DY thanks INTAS (YS Fellowship Program Ref.Nr 03-55-2050) for
financial support of this research and for funding his stay in Florence, Italy. Financial support from
the Research and Educational Center of the Kazan State University - REC 007 (Y1-C-07-06) and
Russian Foundation for Basic Research (RFBR 06-03-32247-a) is also gratefully
Reference
[1] M. Peruzzini, L. Gonsalvi, A. Romerosa, Chem. Soc. Rev. 2005, 34, 1038.
[2] M. Di Vaira, S. Seniori Costantini, P. Stoppioni, P. Frediani, M. Peruzzini, Dalton Trans., 2005, 2234 and refs therein
[3] M. Di Vaira, S. Seniori Costantini, P. Stoppioni, P. Frediani, M. Peruzzini, Acta Cryst. 2005, A61, C303-P.07.01.37.
Book of abstracts, XX th IUCR Congress, Florence, Italy, 2005
[4] Y. Peng, H. Fan, H. Zhu, H. Roesky, J. Magull, C. Hughes, Angew. Chem., Int. Ed. Engl., 2004, 43, 3443 and refs
therein.
[5] A.R. Fox, R.J. Wright, E. Rivard, P.P. Power, Angew. Chem., Int. Ed. Engl., 2005, 44, 7729 and refs therein.
[6] F. Cecconi, C.A. Ghilardi, S. Midollini, A. Orlandini, J. Am. Chem. Soc. 1984, 106, 3667.
[7] D. Yakhvarov, P. Barbaro, L. Gonsalvi, S. Mañas, S. Midollini, A. Orlandini, M. Peruzzini, O. Sinyashin, F.
Zanobini, Angew. Chem., Int. Ed. Engl., 2006, 45, 4182
RT

O-80
ENVIRONMENTALLY BEING CHEMICAL CONVERSION OF CO2 INTO ORGANIC
CARBONATES CATALYZED BY PHOSPHINIUM SALTS
J.S.Tian, C.X.Miao, J.Q.Wang, F.Cai, Y.Du, Y.Zhao, L.N.He*
State Key Lab of Elemento-organic Chemistry, Nankai University, Tianjin, 300071, P. R. China
Dimethyl carbonate (DMC), one of useful organic carbonates, has been drawing much attention
as a safe, noncorrosive, and environmentally friendly building block for the production of
polycarbonate and other chemicals. Also, DMC is of interest as an additive to fuel oil owing to the
high octane number, reducing particulate emission from diesel engines. Therefore, development of
DMC production technology and fuel properties has become important for oil and chemical
industry. A considerable effort has been devoted to the non-phosgene accesses to DMC. In this
context, the two-step transesterification process is very attractive in view of the so-called
“Sustainable Society’’ and ‘‘Green Chemistry’’.
Cat.I: BrBu3PPEG6000PBu3Br; Cat. Ⅱ: K2CO3/ PEG6000; Cat.: K2CO3/
BrBu3PPEG6000PBu3Br
Simple process for DMC synthesis from CO2, epoxide and MeOH
The cycloaddition of propylene oxide and CO2 to form propylene carbonate promoted by
phosphonium salt convalently bound to polyethylene glycol (PEG), and the transesterification of
propylene carbonate with methanol to DMC mediated by PEG-supported K2CO3, were separately
investigated. Single supported catalyst (K2CO3/BrBu3PPEG6000PBu3Br) was shown to be active for
DMC synthesis from propylene oxide, CO2 and methanol under mild reaction conditions, even
under low CO2 pressure (2 bar). The effects of various reaction variables on the activity and
selectivity performance were discussed in details. The catalyst was readily separated and reused
without catalyst leaching detected by 31 P NMR. Notably, excellent yield of DMC and complete
conversion of propylene carbonate were reached under optimized reaction conditions. This
procedure was also successfully applied to the synthesis of other dialkyl carbonates, and eliminates
the requirement for toxic and wasteful feedstocks such as phosgene and carbon monoxide.
References
[1] a) M. A. Pacheco, C. L. Marshall, Energy Fuels,1991, 11, 2; b) P. Tundo, Pure Appl. Chem., 2001, 73,1117; c) S.
Fujita,B.M. Bhanage, Y.Ikushima, M.Arai, Green Chem., 2001, 3, 87.
[2] a) J. C. Choi, L. N. He, H. Yasuda, T. Sakakura, Green Chem., 2002, 4, 230; b) J. S. Tian, J. Q. Wang,J. Y. Chen, J.
G. Fan,F. Cai, L. N. He,Appl. Catal. A: Gen., 2006, 301(2), 215; c) J. Q. Wang, X. D.Yue, F. Cai, L. N. He, Catal.
Commun.,2007, 8, 167; d) J. Q. Wang, D. L. Kong, J.Y. Chen, F. Cai, L. N.He, J. Mol. Catal. A: Chem., 2006, 249,
143; e) Y. Du, J.-Q.Wang, J.-Y. Chen, F. Cai, J.-S. Tian, D.-L.Kong, L.-N. He,Tetrahedron Lett., 2006, 47(8), 1271;
f) Y. Du, F. Cai, D. L. Kong,L. N. He, Green Chem., 2005, 7, 518.
171

O-81
TRANSITION METAL COMPLEXES CONTAINING PHOSPHENIUM AND PHOSPHITE
LIGANDS: FORMATION AND THEORETICAL APPROACH
Hiroshi Nakazawa, * Katsuhiko Miyoshi, # and Keiko Takano §
*Department of Chemistry, Graduate School of Science, Osaka City University, Osaka, Japan, # Department of
Chemistry, Graduate School of Science, Hiroshima University, Higashi-Hiroshima, Japan, and § School of Integrated
Science, Graduate School of Humanities and Science, Ochanomizu University, Tokyo, Japan.
Transition metal complexes containing phosphenium have attracted considerable attention
because of double bond character between M and P. Phosphenium is isolobal with a singlet
carbene and silylene, and a phosphenium ligand shows electrophilicity. For a phosphenium
phosphite complex, two structures (nonbridging and bridging forms) are conceivable. This paper
reports formation of phosphenium phosphite complexes, the preferential structure, and its
theoretical approach.
M
N Me
O
N
P N
O
N
C
P
Mo OMe
O C CO
C
O
N Me
N
O
P N
O
N
C P
Mo OMe
O C
OMe
P
C N
O
N
P
P
OR
+
nonbridging form bridging form
phosphenium phosphite complex
TMSOTf
TMSOTf
172
M
P
P
O C
O C
OR
N N
P
Mo
C
O
1a 1b
2a 2b
+
+
N
N
P
OMe
CO
+
N N
O C
O C
P
Mo
C
O
N
N
P
OMe
OMe
P
N N
OTf
Molybdenum carbonyl complexes with phosphites (1a, 2a) react with TMSOTf to give the
corresponding cationic phosphenium phosphite complexes (1b, 2b) by single OMe - abstraction
from the coordinating phosphite (see eqs 1 and 2). The X-ray structure analyses and the NMR
spectra of the products showed that the original configuration around the Mo is retained and a
nonbridging form is adopted. DFT calculations have been incorporated to study the preference of
the nonbridging form for phosphenium phosphite complexes, together with the preference of the
bridging form for the analogous silylene alkoxysilyl complexes, and found that the bridging
requires larger geometrical changes for phosphenium phosphite complexes than for silylene
alkoxysilyl complexes.
OTf
(1)
(2)

O-82
THE FORMATION OF SPHERICAL GIANT MOLECULES AND
DYNAMIC BEHAVIOUR OF SUPRAMOLECULAR ASSEMBLIES BASED
ON PN LIGAND COMPLEXES
Manfred Scheer*, L. J. Gregoriades, R. Merkle, B. P. Johnson and F. Dielmann
Institut für Anorganische Chemie, Universität Regensburg, Regensburg, D-93040, Germany; e-mail:
manfred.scheer@chemie.uni-regensburg.de
In contrast to common approaches in supramolecular chemistry, our research is focused on the
use of Pn-ligand complexes as connecting units for different metal centres to form coordination
polymers as well as soluble spherical giant clusters. It has already been shown that the tetrahedrane
cluster [Cp2Mo2(CO)4(μ,η 2 -P2)] and the sandwich complexes [Cp*Fe(η 5 -P5)] can act in the reaction
with Cu(I) halides as efficient building blocks for the construction of oligomers, 1D and 2D
polymers, as well as fullerene-like aggregates [1]. Recently we found that the cyclo-P4 containing
ligand complex [Cp''Ta(CO)2(η 4 -P4)] can also be used as a starting unit for the formation of
spherical supramolecular aggregates [2] (see below).
In contrast, the reaction of different Pn-ligand complexes with the Ag I salt of the weakly
coordinating anion [Al{OC(CF3)3}4]¯ leads to novel polycationic polymers, which show in solution
extensive dissociation and exhibit dynamic behaviour [3]. The talk will focus on the structure and
properties of the spherical giant molecules as well as on the dynamic behaviour of the polycationic
polymers.
Reference
[1] a) Bai, J.; Virovets A. V.; Scheer, M., Science, 2003, 300, 781-783. b) Scheer, M.; Bai, J.; Johnson, B. P.; Merkle,
R.; Virovets, A. V.; Anson, C. E.; Eur. J. Inorg. Chem. 2005, 4023-4026.
[2] Johnson, B. P.; Dielmann, F.; Balázs, G.; Sierka, M.; Scheer, M.; Angew. Chem. Int. Ed., 2006, 45, 2473-2475.
[3] Scheer, M.; Gregoriades, L. J.; Virovets, A. V.; Kunz, W.; Neueder, R.; Krossing, I.; Angew. Chem. Int. Ed. 2006,
45, 5689-5693.
173

O-84
THE CHEMICAL PROPERTIES OF ALKALI METALS HEPTAPHOSPHIDES
V.А.Miluykov a , O.G.Sinyashin a , А.V.Kataev a , P.Lonnecke b , E.Hey-Hawkins b
а A.E.Arbuzov Institute of organic and physical chemistry russan academie of sciences, Kazan, Russia,
miluykov@iopc.knc.ru
b
Institut für Anorganische Chemie der Universität Leipzig,
Leipzig, Germany hey@rz.uni-leipzig.de
The alkali metals polyphosphides (homopolyatomic phosphorus clusters, Zintl-anions) are
currently in focus of research both as intermediates of elemental phosphorus transformation in
organic phosphorus compounds and as syntons for construction of polynuclear complexes and
clusters.
We have found that heptaphosphid 1 react with alkyltosylates depend on stoichiometry of
reagents with formation of mixture of symmetric and asymmetric isomers of heptaphosphine 2 or
asymmetric sodium dialkylheptaphosphide 3 only.
R
P
P
P P
P
3Na
P
P
P
P
P P
P
P
P + 3RTos
R
R
R
P P
P
asym, sym
P Na
R
P P
P
asym
+ 2RTos
3 1
2
We have also found a new reaction of heptaphosphide 1 with cyclopropenylic complexes of
nickel - formation of sodium 1,2-diphosphacyclopentadienide.
P
P
P P
3Na
P P
P
L = PhMe 2P, none
Ph
+
Ph
Ni
L Br
L
Ph
Ph
Ph
-
P P
Na
Ph
The protonation of 1,2-diphosphacyclopentadienide anion lead to C-H phosphadiene which is
involved in anomaly [2+2] cycloaddition reaction with formation
rac-trans-1,2,6,7-tetraphospha-3,4,5,8,9,10-hexaphenyltricyclo[5.3.0.0 2,6 ]-3,9-decadien withy high
yield.
Ph
Ph
-
P P
Na
Ph
[H + ]
Ph
Ph
P P
Ph
H
174
P P
Ph
Ph
Ph
P P
Ph
H P
P
H
Ph
The authors thank the Deutsche Forschungsgemeinschaft (436RUS 113/760/0-1) and RFBR
(04-03-04102) for financial support of this work.
Ph
Ph
H
Ph
Ph

O-93
SURFACE PROPERTIES AND CATALYTIC ACTIVITY OF SODIUM ZIRCONIUM
PHOSPHATE IN DEHYDRATION OF METHANOL TO DIMETHYL ETHER
M.V. Sukhanov a , M.M. Ermilova b , N.V. Orekhova b , V.I. Pet'kov a , G.F. Tereschenko b
a Nizhni Novgorod State University, Nizhni Novgorod, Russia, 603950
b Topchiev Institute of Petrochemical Synthesis, Moscow, Russia, 119991
The development of competitive, effective, and environmentally safe fuels is among the global
trends of progress in chemistry. Dimethyl ether (DME) has received a worldwide attention as a
clean alternative fuel for diesel engines since it has a thermal efficiency equivalent to the traditional
diesel fuel, lower NOx emission, lesser carbon particulates, near-zero smoke and lesser engine noise.
In addition, DME is used as a raw material for making chemicals. At present, DME is produced on
the commercial scale by dehydration methanol on mechanical mixtures of aluminum, silicon, and
boron oxides or on molecular sieves. It is still a topical task to develop new catalyst for this process,
which should be more active, selective, and less subject to coking.
Zirconium-containing phosphates with a structure of the sodium zirconium phosphate
(NaZr2(PO4)3, NZP) are of interest as catalysts for dehydration of alcohols because of the high
stability of their structural skeleton, which ensures their resistance to action of water at high
temperature and enables regeneration of a catalyst at elevated temperatures without any changes in
its phase composition. The presence work has been examined the surface area, and surface acid
properties of sodium zirconium phosphate and their influence on methanol dehydration to DME.
Influence of the temperature synthesis of catalyst on methanol dehydration was also studied.
The samples of sodium zirconium phosphates were prepared by the precipitating method starting
from the following reagents: NaNO3, ZrOCl2·8H2O and H3PO4. Precipitates were dried at 353 and
473 K and thermally treated from 873, 1073 and 1273 K during at 24 h without intermediate
regrinding. Phosphate samples were characterized using X-ray powder diffraction, infrared
spectroscopy and microprobe analysis. The BET specific surface areas of the samples were
determined. The acid properties were measured by TPD of NH3. Dependence of specific surface
area and acid properties of sodium zirconium phosphate from temperature treated of sample was
founded.
The conversion of methanol was studied in a convenient Ar-flow system, operated at atmospheric
pressure, in the temperature range from 450 to 750 K. The products of alcohols conversions were
analyzed by gas chromatography. The sample of sodium zirconium phosphates, which thermally
treated from 873 K, was shown the highest specific surface area, acid properties, and catalytic
activity in dehydration of methanol. The alcohol conversion on this sample approaches the
equilibrium value 88-90 % at the 600 K. Dependence of methanol conversion from reactor
temperature (from 450 to 750 K range) and from of flow rate of the alcohol vapor at a reactor (from
0.2 to 1.3 ml·min-1) were founded. It was shown that the sodium zirconium phosphate maybe
compare well with known commercial catalysts for methanol dehydration [1, 2].
The work is supported by the Russian Foundation for Basic Research (Project № 06-03-08064).
References:
[1] V. Vishwanathan, Hyun-Seog Roh, Jae-Woo Kim, and Ki-Won Jun, Catal. Lett. 2004. V. 96. P. 23-28.
[2] F. Yaripour, F. Baghaei, I. Schmidt, J. Perregaard, Catal. Com. 2005. V. 6. P. 147-152.
175

P-10
DESIGNING NEW METALLO-ORGANIC CATALYSTS FOR THE ASYMMETRIC
PHOSPHO-ALDOL REACTION
Alexandra C. Gledhill, Tracy D. Nixon, Terence P. Kee
School of Chemistry, University of Leeds, Woodhouse Lane, Leeds LS2 9JT, UK
Email: chm1acg@leeds.ac.uk
The enantioselective hydrophosphonylation of carbonyls is a highly valuable phospho-transfer
reaction for the synthesis of α-functionalised phosphonate esters which have a large number of
applications in bioorganic science including anti-viral agents, anti-biotics, anti-tumour activity,
transition state models, nucleotide technology and biophosphate mimics. For each of these
applications, the stereochemistry of the phosphonate is crucial to elicit the required properties.
Through the manipulation of catalysts it is possible to control asymmetry and enantioselectivity of
this reaction.
O
RO
P
H
RO
H
O
RO
RO
P
CAT CAT
O
R' H
176
O
RO
P
RO
Here we describe how, through exploration into the synthesis and characterisation of aluminium
complexes based upon the (R,R)-salcyan framework and by applying such complexes as catalyst
precursors for the homogeneous phospho-aldol reaction, increased stereocontrol can be achieved
with {(R,R)-[salcyan( t Bu)2]Al(μ-OH)}2 affording products with e.e. ≤ 62% and preliminary tests
showing that ligands adding extra steric bulk and offering a greater degree of alkyl branching.
Molecular modelling has been carried out using Hyperchem 7.0 (Hypercube, Florida) at the
semi-empirical PM3 level the results of which have enabled us to identify a number of complexes
as potential catalysts for the phospho-aldol reaction which are to be synthesised and tested for their
catalytic ability.
Scheme 1: The currently accepted mechanistic overview of the phospho-aldol reaction for the
synthesis of α-functionalised phosphonate esters.
H H
N
Al
N
O O
OH
R'
O
H
RO
RO
O
P
R'
OH

P-15
ELECTROSYNTHESIS OF METAL PHOSPHIDES ON THE BASIS OF
WHITE PHOSPHORUS
Budnikova Yu.H. * , Krasnov S.A., Gryaznova T.V., Tazeev D.I., Sinyashin O.G.
Institute of Organic and Physical Chemistry of Russian Academy of Sciences, Kazan, Russia,
e-mail: yulia@iopc.knc.ru
Reduction of white phosphorus in the coordination sphere of the electrochemically generated
metal(0) complexes with σ-donor ligands was shown to be possible and accompanied by the
transformation of P4 into the metal phosphides [1].
M n+ L + ne M 0 L L = bipy, solvent, M = Ni, Co, Pd, Rh, Ir...
M 0 L + P 4 product [M-P]
6 Ni0L + P4
6 Ni0PPh3 + P4
+ 2e
Ni(II)L
+ P4
Ni(0)L
Ni(II)(P4)L
2 Ni3P2L L = bipy, phen
DMF
-PPh3
+ P4
Ni3P2L
+ 2e
177
2 Ni3P2(DMF)
S spec. = 200 m2/g
L = bipy
Initially the black colloidal solution of stabilized Ni-clusters was formed. One day later nickel
deposits precipitates. Scanning tunnel microscopy was used for determine the size of the
nanoparticles -~15-20 nm. The surface area of the ultrafine amorphous materials, manufactured in
traditional way, e.g., by the vapor deposition, is usually very small, 0.1-0.01 m 2 /g [12]. It is too
small to use these materials in the industrial catalysis due to low productivity per the catalyst weight.
The ultrafine amorphous alloys, obtained by chemical reduction, has more large surface area –
30-130 m 2 /g and much more effective. We detected that phosphide Ni3P2bipy, prepared from the
electrochemically generated Ni(0)bipy and white phosphorus, has a very large surface area – 200
m 2 /g, i.e. presents the so-called ‘ultrafine material’. Thus, the proposed synthetic procedure allows
to obtain the ‘ultrafine materials’ hard to be proceeded in the regular way, what allows to use these
materials as the basis for the development of new catalysts.
Acknowledgments: RFBR (04-03-32830, 05-03-08039 ofi-p), INTAS.
Reference
[1] Yu.H. Budnikova, D.I. Tazeev, B.A. Trofimov, O.G. Sinyashin. Electrochem. Comm. 6 (2004) 700–702

P-76
NOVEL SYNTHETIC ROUTES TO PHOSPHORUS ORGANIC COMPOUNDS ON THE
BASIS OF THE ELEMENTAL PHOSPHORUS (P4)
O. G. Sinyashin, E. S. Batyeva, E.V. Platova, E.K. Badeeva, L.I. Kursheva
A.E.Arbuzov Inatitute of Organic and Physical Chemistry of Russian Academy of Sciences, Kazan Scientific Center,
Kazan, Arbuzov Str.8, 420088, Russi;a.
Reactions of elemental phosphorus (P4) with proton containing reagents (water, diols, thiols) in
the presence of compounds with bidentate character, which promote the cleavage of the P4
tetrahedron, have been studied. As such kind of compounds we have proposed and used amines,
which form appropriate complexes upon the interaction with organic (ethylene oxide) and inorganic
(sulfur) reagents as well as bidentate complexes of trialkyltrithiophosphites with transition metal
halides.
Reaction of the P4 with water in the presence of tertiary ammonium bases, i.e.,
β-hydroxyethyltrimethylammonium (choline), has been performed. The latter is formed at the
interaction of trimethylamine with ethylene oxide in aqueous medium, and promotes the cleavage of
the P4 tetrahedron. The reaction is accompanied by the elimination of hydrogen (H2) instead of
phosphine, as it is usually performed in the presence of other tertiary amines (triethyl-, tributyl-,
dimethylbenzyl amines). The same result was obtained in the reaction of P4 and trimethylamine,
ethylene oxide and water. This method is proposed as the general approach for the synthesis of
phosphoric acids and their derivatives on the basis of the reaction of elemental phosphorus (P4) with
water in the presence of tertiary ammonium base - β-hydroxyethyltrimethylammonium (choline).
Thus, novel convenient technological method for the preparation of hypophosphiteβ-hydroxyethyltrimethylammonium
(cholinehypophosphite) from white phosphorus, choline and
water, or from white phosphorus, trimethylamine, ethylene oxide and water has been developed.
It has been shown for the first time that interaction of white phosphorus and sulfur with aliphatic
mercaptans in the presence of amines - (diethyl-, triethylamine, piperidine)- results in the new
pathway – the formation of ammonium salts 1,2,3,4-tetrathiol-1,2,3,4-tetrathiontetraphosphetanes.
Reactions of white phosphorus and sulfur with 1,2-ethylene- and 1,3-propylene glycols proceed
analogously in the presence of piperidine. On the contrary the formation of tetrathiophosphates is
observed in reaction of white phosphorus and sulfur with aliphatic mercaptans in the presence of
Cu(I) halide complexes with thiophosphites.
Acknowledgements
The grants of the Russian Foundation for Basic Research (06-03-32180) and Program7 of the DCMS RAS are
gratefully acknowledged.
178

P-99
REACTION OF 2-R-BENZO[D]-1,3,2-OXAZAPHOSPHORIN-6-ONES WITH
HEXAFLUOROACETONE
V.F.Mironov 1,2 , Yu.Yu.Borisova 1 , L.M.Burnaeva 1 , A.T.Gubaidullin 2 , I.A.Litvinov 2 ,
G.A.Ivkova 1 , N.K.Amerkhanova 1 , I.V.Konovalova 1
1 Kazan State University, Kremlevskaya Str. 18, Kazan, 420008 Russia
2 A.E.Arbuzov Institute of Organic and Physical Chemistry, Russian Academy of Sciences,
Arbuzov Str. 8, Kazan, 420088, Russia, e-mail: mironov@iopc.knc.ru
The six-membered cycle of 2-R-benzo[d]- and 2-R-naphtho[2,3-e]-1-3-2-dioxaphosphorin-4-ones
undergoes the cycloexpansion in reaction with activated carbonyl compounds to give
the unsymmetrical functionalized seven-membered heterocycles, namely benzo[d]- and
naphtho[1,2-f]-1,3,2-dioxaphosphepines. These compounds obtained with using of
hexafluoroacetone can be used in further synthesis of the fluorinated ketones, which are not
available for obtaining by the other methods. Here the new results concerning the application of the
reaction of hexafluoroacetone with the cyclic phosphorylated derivatives of phenylantranilic acid
are reported. Benzo[d]-1,3,2-oxaazaphosphorin-6-ones (1,2) were synthesized for the first time by
the reaction of phenylantranilic acid with alkyl- and alkoxydichlorophosphines in the presence of
NEt3. The reaction of compounds (1,2) with hexafluoroacetone was found to yield the new
heterocycles – substituted benzo[d]-1,3,2-oxaazaphosphepines (3,4). Compound (5) was obtained as
a result of hydrolysis of (3,4).
1,2
Ph
N R
P
O
O
O
CF3CCF3
Ph O
N R
P
O
CF3
3,4 O CF3
H2O
5
R = Ph (1,3), OEt (2,4)
179
NH Ph
OH
The reaction includes a nucleophilic attack of phosphorus on carbon with the formation of
P + –C–O – -betaine, P + –C–O – → P + –O–C – -rearrangement and intramolecular attack of the carbon
anionic center on encocyclic carbonyl group.
C
C
C 7
P 2
O 1
C 8
O 2
O 7
C 10
F 1
F 2
F 3
F 4
N 3
C 6a
C 6b
F 5
F 6
C
C
C
C
C 9 C
The structure of (3,4) was confirmed by 1 H, 13 C, 31 P NMR and IR spectroscopy as well as by the
single crystal X-ray diffraction (see figure). The conformation of phosphepine’s heterocycle is a
distorted boat with planar fragment N 3 C 6a C 6b C 7 .
Thus, the proposed synthetic approach including the reaction between the P(III)-cyclic
derivatives of hydroxycarbonic acid, like heterocycles (1,2), and carbonyl compounds is perspective
for the synthesis of phosphepines and fluorinated ketones.
C
C
C 3
C 6
C 4
C 5
C
C
C
O
CF3
CF3

P-117
STUDY ON STRUCTURE AND PROPERTIES OF AMORPHOUS Ni-Cu-P ALLOY
COATINGS PREPARED BY ELECTROLESS PLATING
Xu Ruidong, Wang Junli,Guo Zhongcheng
Faculty of Materials and Metallurgical Engineering, Kunming University of Science and Technology, Kunming 650093,
China
The components, phase structure and hardness of Ni-Cu-P alloy coatings prepared by electroless
plating, were studied. The results show that the nickel and phosphorus contents in coating decrease
and copper content increases with increasing CuSO4·5H2O concentration in bath. Owning to the
characteristic of priority of Cu deposition, which makes Cu/Ni mass ratio in coating be higher than
that in bath. X-ray diffraction displays that Ni-Cu-P alloy coating is amorphous state as-deposited
and heat-treated at 300℃, there are some thermodynamics equilibrium phase deposited such as
Ni3P and Cu3P in coating after that heat treatment temperature is higher than 400℃, and it has
turned into crystalline state. The hardness test shows that when heat treatment temperature is lower
than 400℃, the structure of coatings changes and the distortion in the crystal lattice gets serious,
making the Ni-Cu-P alloy coating hardness increase. At 400℃, since a large number of Ni3P phase
appears and precipitation hardening occurs, the coating hardness reaches peak value (845Hv). With
continuously increasing heat treatment temperature, crystalline particles of nickel solid solution
grow and Ni3P particles aggregate and coarsen, and the composite coating softens, making the
coating hardness decrease.
180

P-139
DETERMINATION OF DEXAMETHASONE SODIUM PHOSPHATE IN MEDICAMENT
BY FLUORESCENCE PROBE OF Tb 3+ -TIRON COMPLEX
Chaobiao Huang a, *, Zhenrong Yu b , Libin Zhou a
a College of Chemistry and Life Science ,Zhejiang Normal Univiersity , Jinhua 321004,China
b Deqing No.3 High School,Zhejiang,China
A sensitive method by fluorescence quenching for the determination of dexamethasone sodium
phosphate is proposed.The method is based on the ability of phosphate to inhibit the formation of a
strong fluorescent complex of Tb 3+ with Tiron.The fluorescence intensity trend equilibrium after
20 minutes reaction of dexamethasone sodium phosphate and Tb 3+ -tiron complex. The optimal
conditions for the determination of dexamethasone sodium phosphate are studied,and the
possibilities of spectrofluorimetric measurements of the system are studied under optimal
conditions (pH 7.5 in 0.01 mol/L Tris-HCl bufer).The linear range of the determination is 2.5×10 -
7 -6 -8
~4×10 mol/L and the detection limit is 6.2×10 mol/L, and the RSD of 11 times determination
are 2.2% and 0.8% for 5×10 -7 mol/L and 1×10 -6 mol/L, respectively.The method has been applied
to determine dexamethasone sodium phosphate in dexamethasone sodium phosphate injections.
Keywords: Tb 3+ -tiron complex, fluorescence quenching, dexamethasone sodium phosphate,
medicament
References
1 Editorial Committee of Pharmacopoeia of People’s Republic of China. Pharmacopoeia of People’s Republic of
China(Part II).Beijing:Chemical Industry Press,2005
2 Pang Yinuo,Zhang Yan,Zhang Zhirong,et al. Chin Hosp Pharm J.,2003,23(5):257~260
3 Bi Xueyan,Li Liping,Li Li,Yu Weibing. Pharm J Chin PLA.,2006,22 (3):235~236
4 Yang Yanwei,Zhu Ying,Zhang Weiqiang et al. J Environ Health., 2006, 23 (3):264~266
181

Symposium 4
Nucleotides and Oligonucleotides-From Basic to
Medicinal Applications; Biological Aspects
of Phosphorus Chemistry

KL-14
THE CHEMICAL BIOLOGY OF HISTIDINE TRIAD NUCLEOSIDE
BINDING PROTEINS
Carston R. Wagner
Departments of 1Medicinal Chemistry and 2Chemistry, University of Minnesota, Minneapolis,
Minnesota 55455, USA, *wagne003@umn.edu
HIT enzymes are a ubiquitous superfamily consisting primarily of nucleoside phosphoramidases,
dinucleotide hydrolyases and nucleotidylyl transferase. The distinguishing feature of these enzymes
is an active site motif composed of the sequence, His-X-His-X-His-XX, where X is a hydrophobic
residue. Three primary families of HIT have been identified. The first and most ancient is the
histidine triad nucleotide binding protein (Hint). Hint homologs isolated from rabbit, human,
chicken, yeast and E. coli. Mammalian Hint1 has been suggested to have tumor suppressor activity
in a hint1-knock out mice model and human non-small cell lung carcinoma cells. Related to this
observation, the expression of hHint1 has been shown to be a potential regulator of apoptosis.
Recently, we and others have demonstrated that Hints are purine nucleoside phosphoramidases. In
addition, we have discovered that Hints interact with amino acyl-tRNA synthetases by efficiently
hydrolyzing amino acid adenylates. These are first example of natural substrates for these enzymes.
Our laboratory has engaged in designing anticancer and antiviral pronucleotide based on our
understanding of Hint structure-activity relationships. We are also engaged in elucidating the
biological mechanism and function of Hints. The lecture will discuss both aspects of our research.
183

KL-16
STUDIES ON MODIFIED OLIGONUCLEOTIDES
Lihe Zhang
Peking University, School of Pharmaceutical Sciences 38 Xue-Yuan Road, Beijing, 100083, P.R.China
Email: zdszlh@mail.bjmu.edu.cn
184

KL-21
KINASE AND KINASE INHIBITOR AS ANTICANCER THERAPEUTICS
Chen Li
Roche R&D Center (China) Ltd., 720 Cai Lun Road, Building 5, Pudong, Shanghai 201203, P.R. China
185

KL-40
STEREOCHEMISTRY OF ENZYME-ASSISTED P-N BOND CLEAVAGE IN
ADENOSINE 5'-PHOSPHORAMIDATES AND –PHOSPHORAMIDOTHIOATES
Agnieszka Krakowiak, Renata Kaczmarek, Janina Baraniak, Michał Wieczorek
and Wojciech J. Stec
Department of Bioorganic Chemistry, Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences,
112 Sienkiewicza Str., 90-363 Łódź, Poland
The enhancement of the therapeutic activity of antiviral and anticancer nucleoside analogs and
suppression of their side-effects is a continuing goal of several research establishments. Several
prodrug approaches have been designed including phosphoramidate di- and mono-esters derived
from amino acids. Because of the suggestion that Hint hydrolases might be responsible for
nucleoside monophosphoramidate prodrug activation in vivo,1 elucidation of mechanism of
phosphoramidase activity appeared important.
Here we report on the stereochemistry of the reaction catalyzed by rabbit Hint1 using the
P-diastereoisomers of adenosine-5’-O-[N-(tryptophanylamide)]phosphoramidothioate (AMPS-Trp).
Stereocontrolled synthesis of the diastereoisomer substrates of rHint1 was feasible via our
oxathiaphospholane approach.2 The absolute configuration at phosphorus of individual species has
been assigned by X-ray analysis. We performed the experiment with rHint1 degradation of
RP-AMPS-Trp to the AMPS-[18O] in the presence of H218O, sufficient for stereochemical
analysis designed earlier in this Laboratory.3 MALDI-TOF MS analysis of the final product
unambiguously proved the presence of [18O] isotope in the resulting heptamer (d[(AP)5A]PS18OA.
Such result indicated that the overall process of the cleavage the P-N bond proceeds with
stereochemical retention of configuration what is consistent with the participation of a covalent
enzyme-substrate complex. To our best knowledge this is the first report of the stereochemical
course of enzymatic P-N bond scission. The result is in agreement with the mechanism of action of
two other P-O cleaving enzymes belonging to different branches of the HIT superfamily, namely
Fhit hydrolase (second branch) and galactose-1-phosphate uridylyltransferase (GalT, third branch).4
Additionally, we observed extensive loss of sulfur from AMPS as a sequential process
accompanying P-N bond cleavage in the action of Hint-1 on nucleoside
5’-O-phosphoramidothioates, and our preliminary results have shown that this desulfuration process
is not ribonucleotide specific. Since the Hint enzyme has been shown to have homologs in all forms
of life,4 our observations may become pertinent to the further elucidation of the metabolism of
nucleoside 5’-O-phosphorothioates, formed e.g. as primary products of degradation of antisense
oligonucleotide phosphorothioates by 3’-exonucleases. Additional studies concerning the
elucidation of the mechanism of the enzyme-catalysed desulfuration process are in progress.
Reference
1.P. Bieganowski, P. N. Garrison, S. C. Hodawadekar, G. Faye, L. D. Barnes and C. Brenner, J. Biol. Chem., 2002, 277,
10852-10860.
2.W. J. Stec, B. Karwowski, M. Boczkowska, P. Guga, M. Koziołkiewicz, M. Sochacki, M. W. Wieczorek, and J.
Błaszczyk, J. Am. Chem. Soc., 1998, 120, 7156-7167.
186

KL-42
POLYPHOSPHATES FOR DRUG AND GENE DELIVERY
Renxi Zhuo, Shiwen Huang
Key Laboratory of Biomedical Polymers, Ministry of Education, Department of Chemistry, Wuhan University, Wuhan
430072, P.R.China
Email: bmp@whu.edu.cn
Synthetic biodegradable polymers, such as aliphatic polyesters, aliphatic polycarbonates,
poly(ortho esters),polyanhydrides,polyphosphates etc, have been widely investigated and
applied in biomedical field. Among the current biodegradable polymers, polyphosphates have
attracted great attention because of their biocompatibility and pendant functionality. Additionally,
polyphosphates, as copolymerization components, can increase the solubility of copolymers in
common solvents and lower the glass-transiton temperature. As a result, the processability of
copolymers can be greatly improved. We here report the synthesis of a series of novel
polyphosphates and application in drug and gene delivery.
Biodegradable polyphosphates copolymers were synthesized by ring-opening copolymerization
of alkyl ethylene phosphate with a variety of cyclic monomers, such as D, L-lactide, cyclic
carbonate, p-dioxanone. It was found that the introduction of phosphates into polylactide,
polycarbonate and poly(p-dioxanone) would enhance the degradation rates of the copolymers.
Water-soluble cationic polyphosphoramidates (PPAs) with different pendant primary amino
groups were synthesized by ring-opening polymerization of 4-methyl-2-oxo-2-hydro
-1,3,2-dioxaphospholane, followed by reacting with N-trifluoroacetyl diamine or
N,N’-bis(trifluoroacetyl) triamine in the presence of CCl4, and deprotected in ammonia. These
novel PPAs showed lower cytotoxicity than PEI and PLL, and mediated efficient in vitro and in
vivo DNA transfection. In order to increase the stability under physiological conditions as well as in
vivo transfection efficiency of PPA/DNA complexes, we conjugated PPA with galactose-end PEG
(Gal-PEG-PPA), and evaluated its in vitro and in vivo transfection efficiencies. It is found that the
incorporation of PEG and galactose into PPA decreases the cytotoxicity, improves the tissue
compatibility, and greatly enhances the transgene expression in mouse and rat liver.
187

KL-46
SYNTHESIS AND BIOCHEMICAL ACTIVITY OF NEW
OLIGONUCLEOTIDE ANALOGS
Marvin H. Caruthers
University of Colorado, Department of Chemistry and Biochemistry,
Boulder, CO 80309-0215, USA
Deoxyoligonucleotides containing phosphonoacetate and thiophosphonoacetate internucleotide
linkages are synthesized from appropriately protected deoxynucleoside acetic acid
phosphinoamidites. By additional use of standard deoxynucleoside phosphoramidites, synthesis
could be extended to chimeras having phosphate or thiophosphate internucleotide linkages as well.
These oligomers are stable to degradation by nucleases, generate A-form duplexes with
complementary RNA, and stimulate RNase H activity. As acetic acid esters, phosphonoacetate
oligomers stabilize uptake of interfering RNA (as duplexes) by HeLa, MDCK, K562 and Jurkat
cells in the absence of cationic lipid. Moreover this siRNA is biologically active. The synthesis
of phosphonoformate deoxyoligonucleotides can be carried out on a Q-linker support using
appropriately protected formic acid phosphinoamidites. These synthons are protected on the
formic acid ester with diphenylmethylsilylethyl and with 9-fluorenylmethyloxycarbonyl on the
exocyclic amines. With this strategy, removal of all protecting groups as well as cleavage of the
support linkage is possible using mild conditions (TEMED-HF at pH 8.6). By the use of formic
acid phosphinoamidites in combination with standard deoxynucleoside H-phosphonates, chimeras
having phosphonoformate and phosphate internucleotide linkages are synthesized. The resulting
oligomers yield A-form duplexes with complementary RNA, are resistant to nuclease degradation,
and stimulate RNase H activity 2-6 fold relative to the same unmodified heteroduplex. Unlike
chimeric phosphonoacetates, phosphonoformate oligomers form duplexes with natural RNA that
are dramatically more stable (10 °C-11 °C) than similar unmodified duplexes.
Borane phosphonate deoxyoligonucleotides are synthesized from 5'-O-benzhydroxybis(trimethoxy)silyl-2'-deoxynucleoside-3'-phosphoramidites.
The exocyclic amines of adenine and
cytosine are protected with dimethoxytrityl and trimethoxytrityl, respectively, whereas guanine
protection is with N2-(9-fluorenylmethoxy carbonyl). Thymine is protected with N3-anisoyl.
Using these synthons and under standard conditions via activation with tetrazole, cyclic
condensations in excess of 99% are observed. Oxidation with either THF•BH3 or a peroxyanion
solution followed by cleavage of the silyl ether with fluoride completes a cycle. Following
synthesis of an appropriate oligomer, protecting groups are removed using sequentially acetic acid,
a dithiolate and ammonium hydroxide. Oligodeoxynucleotide 10mers having any combination of
borane phosphonate and phosphate internucleotide linkages are synthesized in isolated yields of
70-80% and characterized by phosphorus NMR and mass spectrometry.
188

IL-41
STUDY OF ARTIFICIALLY SELECTED BIOCATALYSTS COVALENTLY MODIFIED
BY ORGANOPHOSPHORUS COMPOUNDS
Alexander G. Gabibov †, Andrey V. Reshetnyak †, ‡ , Maria Francesca Armentano § , Natalia A. Ponomarenko † , Oxana
Durova † , Rustam Ziganshin † , Marina Serebryakova # , Vadim Govorun # ,Gennady Gololobov, Herbert C. Morse III * ,
Alain Friboulet ** , Sudesh P. Makker ‡ and Alfonso Tramontano §
† Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry RAS, 16/10, Miklukho-Maklaya str, Moscow, 117871,
Russia. § University of California, Davis – School of Medicine, Davis, CA 95616, USA.
‡ Department of Chemistry, Lomonosov Moscow State University, Moscow, 119899, Russia.
# Proteom Center of Russian Academy of Medical Sciences, Pogodinskaya str., Moscow, Russia.
* Laboratory of Immunopathology, National Institute of Allergy and Infectious Diseases, National Institute of Health,
5640 Fishers Lane, Rockville, MD 20852, USA. ** CNRS UMR 6022, Compiègne Technological University, BP 20529,
Compiègne Cedex, France.
The adaptation of biocatalysts by genetic diversification and functional selection is a promising
new direction for drug discovery, molecular medicine and material science (1). More broadly,
chemical selection applied to vast unbiased molecular libraries could give rise to artificial enzymes,
affording important insight to the evolution of biocatalysis (2). Here we examine the enzyme-like
functionality and structure of molecules identified in a reactivity-based search of a diversified
protein repertoire represented by a synthetic phage-display human Ig V (scFv) gene library (2).
Among the scFv selected by reaction with a phosphonate diester five clones had similar kinetic
reactivity with kapp of 0.012 – 0.035 min -1 while a sixth (A.17) was nearly an order of magnitude
more reactive (kapp = 0.32 min -1 ). Dissociation constants varied from 50 to 200 μM. Mass
spectrometry identified nucleophilic Tyr33 at CDR-L1 in a representative clone A.5, whereas the
more reactive A.17 was modified at Tyr37 in FR-L2. Consistently, site-directed mutants
A.5Tyr33Phe and A.17Tyr37Phe were shown to be inactive while A.5 Tyr37Phe and A.17
Tyr33Phe retained covalent reactivity. Furthermore, A.17 displayed specific amidase activity with
Phe-MCA (kcat = 9.2 ± 0.5 x 10 -4 min -1 , Km = 50 μM). Mutant A.17Y37F was catalytically
inactive suggesting covalent catalysis in the amidase mechanism. A VL germline with a highly
conserved CDR3 was represented in 9/10 clones, whereas A.17 utilized a different VL. Greater
diversity was seen in VH sequences, although Asn or Gln at position 105 in CDR-H3 was highly
conserved in reactive clones and absent in non-reactive clones. Molecular modeling and docking in
silica showed good complementarity at the active site with the phosphonate modifier and Phe-MCA
substrate and further suggested the participation of Asn/Gln105 in an active site dyad with the
nucleophilic Tyr. These sites may recapitulate a primitive catalytic apparatus in the origin of
enzyme activity.
189

IL-42
THERMOSENSITIVE PHOSPHATE/THIOPHOSPHATE PROTECTING GROUPS AND
THE DEVELOPMENT OF THERMOLYTIC OLIGONUCLEOTIDE PRODRUGS
Andrzej Grajkowski, Cristina Ausín, Serge L. Beaucage
Center for Drug Evaluation and Research, Food and Drug Administration, Bethesda, Maryland, USA
Our research efforts have focused in recent years on the design and development of heat-sensitive
groups for 5’-hydroxyl1 and phosphate/thiophosphate2-6 protection in an attempt to implement a
“heat-driven” process for solid-phase oligonucleotide synthesis. Thus, thermosensitive groups such
as the 2-(N-formyl-N-methyl)aminoethyl,2 4-oxopentyl,3 3-[(N-tert-butyl)carboxamido]-1-propyl,4
3-(2-pyridyl)-1-propyl,5 2-[N-methyl-N-(2-pyridyl)]aminoethyl,5 and 4-methythio-1-butyl 6 were
employed as P(III) protecting groups for deoxyribonucleoside phosphoramidites, which were
incorporated into oligonucleotides via solid-phase techniques. Given the mild conditions under
which thermolytic phosphate/thiophosphate protecting groups can be removed at near neutral pH,
the use of these groups is attractive for the production of therapeutic oligonucleotides. The
thermolytic deprotection mechanism of these protecting group was investigated and was consistent
with an intramolecular cyclodeesterification reaction.2-6 While the phosphate/thiophosphate
deprotection kinetics of DNA oligonucleotides functionalized with the thermolabile
3-(2-pyridyl)-1-propyl, 2-[N-methyl-N-(2-pyridyl)]aminoethyl, and 4-methythio-1-butyl groups
were relatively rapid (t∞ ~30 min, 55°C),5,6 the deprotection kinetics of oligonucleotides
functionalized with the 2-(N-formyl-N-methyl)aminoethyl phosphate/thiophosphate protecting
group were considerably slower (t∞ ~3 h) at a much higher temperature (90°C).2 Although not
optimal for routine oligonucleotide synthesis, the 2-(N-formyl-N-methyl)aminoethyl
phosphate/thiophosphate protecting group was deemed appropriate for the development of
therapeutic oligonucleotide prodrugs on the basis of its sluggish deprotection kinetics at 37°C (t1/2
~73 h).7 In this context, oligonucleoside phosphorothioates functionalized with the
2-(N-formyl-N-methyl)aminoethyl group for thiophosphate protection exhibited the characteristics
of oligonucleotide prodrugs in that they are uncharged and, thus, inherently resistant to the
hydrolytic activity of nucleases. This class of modified oligonucleotides, unlike most recently
developed oligonucleotide prodrugs, does not require esterases or other intracellular enzymes for
prodrug-to-drug conversion. Only an aqueous environment maintained at 37°C or above is
necessary to efficiently convert oligonucleoside 2-(N-formyl-N-methyl)aminoethyl
phosphorothioate triesters to bioactive oligonucleoside phosphorothioate diesters. This novel
concept in oligonucleotide prodrug development led to the solid-phase synthesis of CpG ODN
fma1555[d(GPS(FMA)CPS(FMA)TPS(FMA)APS(FMA)GPS(FMA)APS(FMA)CPS(FMA)GPS(F
MA)TPS(FMA)TPS(FMA)APS(FMA)GPS(FMA)CPS(FMA)GPS(FMA)T)]as a potential
immunotherapeutic DNA oligonucleotide prodrug,7 where PS(FMA) stands for a
2-(N-formyl-N-methyl)aminoethyl phosphorothioate triester function. CpG ODN fma1555 behaved
as a prodrug by virtue of its conversion to the well-studied immunomodulatory oligonucleoside
phosphorothioate diester CpG ODN 1555 [d(GPSCPSTPSAPSGPSAPSCPSGPSTPS TPSAPS
GPSCPSGPST)] through thermolytic cleavage of the 2-(N-formyl-N-methyl)aminoethyl
thiophosphate protecting group at 37°C. The immunostimulatory properties of CpG ODN fma1555
190

were evaluated in mice challenged in the ear with live Leishmania major metacyclic promastigotes.
Local intradermal administration of CpG ODN fma1555 was as effective as that of CpG ODN 1555
in reducing the size of Leishmania lesions over time.7 In a different infectious model, CpG ODN
fma1555prevented the death of Tacaribe-infected mice (60-70% survival) when administered three
days before infection.7 Interestingly, co-administration of CpG ODN fma1555 and CpG ODN 1555
in this model increased the window for therapeutic treatment against Tacaribe virus infection, and
thus supported the use of thermolytic oligonucleotides as prodrugs in the effective treatment of
infectious diseases. Our results are consistent with the notion that CpG ODN fma1555 behaves as a
prodrug in vivo through an unprecedented thermolytic process. These findings prompted us to
design CpG ODN prodrugs exhibiting either a shorter or longer half-time of thiophosphate
deprotection relative to that of CpG ODN fma1555 for the preparation of effective and long-acting
immunotherapeutic oligonucleotide formulations against various infectious diseases in animal
models. In this regard, the 5’-proximal CpG motif of CpG ODN fma1555 has been functionalized
with a single thermolabile 4-hydroxy-1-butyl (hbu) or 4-thiophosphato-1-butyl thiophosphate (psb)
protecting group.8 These modifications were achieved through incorporation of an activated
deoxyribonucleoside phosphoramidite, carrying a 4-levulinyloxy-1-butyl group for phosphorus
protection, into the oligonucleotide chain during solid-phase synthesis, and through an optional
phosphorylation reaction effected by bis[S-(4,4’-dimethoxtrityl)-2-mercaptoethyl]-N,N-diisopropylphosphoramidite 9
after hydrazinolysis of the 4-levulinyl group. The thermal deprotection kinetics of the hbu and psb
thiophosphate protecting groups were determined in phosphate-buffered saline (pH 7.2) using
dinucleotide models. The thermolytic cleavage of the 4-hydroxy-1-butyl and
4-thiophosphato-1-butyl thiophosphate protecting groups from the dinucleotide model occurred
with a half time of 47 min and 13 min, respectively, at 90 °C or 168 h and 30 h, respectively, at
37°C. Studies assessing cellular uptake and biological activity of the modified CpG ODN fma1555
(CpG ODN hbu1555 and CpG ODN psb1555) are ongoing. Incidentally, the solubility of CpG
ODN psb1555 in water has increased by ~50% relative to that of CpG ODN fma1555. Our findings
thus foster the chemical development of novel, minimally charged, thermolytic oligonucleotide
prodrugs exhibiting an optimal range of prodrug-to-drug conversion half times for optimal
therapeutic outcomes.
References
[1] M.K. Chmielewski, V. Marchán, J. Cieślak, A. Grajkowski, V. Livengood, U. Münch, A. Wilk and S.L. Beaucage, J.
Org. Chem., 68, 10003 (2003).
[2] A. Grajkowski, A. Wilk, M.K. Chmielewski, L.R. Phillips and S.L. Beaucage, Org. Lett., 3, 1287 (2001).
[3] A. Wilk, M.K. Chmielewski, A. Grajkowski, L.R. Phillips and S.L. Beaucage, Tetrahedron Lett., 42, 5635 (2001).
[4] A. Wilk, M.K. Chmielewski, A. Grajkowski, L.R. Phillips and S.L. Beaucage, J. Org. Chem., 67, 6430 (2002).
[5] J. Cieślak and S.L. Beaucage, J. Org. Chem., 68, 10123 (2003).
[6] J. Cieślak, A. Grajkowski, V. Livengood, and S.L. Beaucage, J. Org. Chem., 69, 2509 (2004).
[7] A. Grajkowski, J. Pedras-Vasconcelos, V. Wang, C. Ausín, S. Hess, D. Verthelyi and S.L. Beaucage, Nucleic Acids
Res., 33, 3550 (2005).
191

IL-43
ADVANCING BIOMEDICAL RESEARCH BY DEVELOPMENT OF FLUORESCENT
OLIGONUCLEOTIDE-BASED ASSAYS
Gerald Zon
Applied Biosystems, Advanced Research & Technology,Foster City, CA 94404, USA
Automated solid-phase synthesis of oligodeoxynucleotides (ODNs) based on 5’-dimethoxytrityl
3’-phosphoramidite 2’-deoxynucleoside monomers pioneered by Caruthers and coworkers was
commercially introduced by Applied Biosystems Inc. (ABI) in 1983 as a convenient source of
ODNs for basic research and recombinant DNA technology. Shortly thereafter, ABI introduced
4-colored 5’-fluorescently labeled ODNs for automated Sanger-sequencing of DNA, which was
subsequently improved by development of 2’, 3’-dideoxynucleotide triphosphate terminators having
fluorescence resonance energy transfer (FRET) dyes (BigDye®). ODN primers and BigDye®
technology was used to sequence the human genome in 2001, and thus enabled the era of genomics.
Ready access to synthetic ODN primers for PCR, and development by ABI of FRET-based
TaqMan® probes, has enabled real-time quantification of mRNA for gene expression analysis, as
well as detection of single nucleotide polymorphisms (SNPs). All of these fluorescent
oligonucleotide-based assays are now widely use for basic and biomedical research of human or
other species genomes and transcriptomes. Such analyses of genetic variation have given rise to the
concept of “personalized medicine,” wherein genomic analytical data for an individual is used to
assess predisposition to inherited or somatic diseases, as well as drug efficacy or toxicity. To do this
on abroad scale, the cost of sequencing an individual genome must be greatly reduced, which has
led to the quest for what is called the “$1,000 genome.” ABI has begun development of a novel
technology called Sequencing by Oligonucleotide Ligation and Detection (SOLiD) that offers the
possibility for significantly reduced costs of genomic sequencing. In this massively parallel
approach, short-fragment DNA populations are clonally amplified by emulsion PCR onto 1-micron
beads, which are then enriched and randomly deposited and attached onto glass arrays. The bead
array is then placed into an automated flow-cell where 4-color 5’-fluorescently-labeled probes are
used to interrogate bead-attached DNA-template positions relative to an ODN primer having a
5’-phosphate. Ligase is used to join the 5’-phosphate to the 3’-end of the hybridized probe, and is
followed by washing and then fluorescence detection to identify the base at the interrogation
position. A metal ion-catalyzed cleavage reaction involving a 3’-phosphorothiolate linkage is used
to fragment the ligated probe to release a fluorescent moiety and generate a 5’-phosphate group on
the extended primer for a further ligation. The aforementioned steps define a cycle that is repeated a
number of times. The resultant multiply-extended primer is eluted from the bead-attached DNA
template, and a second primer that is shorter by one base is used to carry out a number of
base-interrogation cycles. This process is repeated to ultimately afford the base-by-base sequence of
the bead-attached DNA template. In the case of 25-base sequence reads by SOLiD, the automated
system under development is projected to provide 1 billion bases of DNA sequence in each run.
192

IL-44
NON WATSON-CRICK STRUCTURE RECOGNITION AND ITS APPLICATIONS
Zhen Xi
National Key Laboratory of Elemento-Organic Chemistry, Department of Chemical Biology, College of Chemistry
Nankai University,Tianjin 300071, P.R.China Email: zhenxi@nankai.edu.cn
Nucleic acids can have richly diverse structures, including hairpins, knots, pseudoknots, triple
helices, loops, helical junctions etc. Such bulged structures in nucleic acids are of general biological
significance. They have been proposed as intermediates in a multitude of processes including RNA
splicing, frame-shift mutagenesis, intercalator induced mutagenesis, imperfect homologous
recombination, as the binding site for the coat protein of bacteriophage, in the ribosomal
synthesizing machinery and in RNAi of pre-microRNA (bulge-RNA hairpin), the precursor of
microRNA. Bulges have also been suggested as binding motifs for regulatory proteins involved
with viral replication, including the TAR region of HIV-1. Additionally, the etiology of at least 31
human neurodegenerative genetic diseases has been attributed to genetic variations in the lengths of
triplet repeats in genomic DNA (e.g. myotonic dystrophy, Huntington’s disease, Friederich’s ataxia,
and fragile X syndrome). The unstable expansion of triplet repeats has been attributed to reiterative
synthesis due to slippage and bulge formation in the newly formed DNA strand. As such,
compounds capable of binding to bulges/hairpin could have significant therapeutic potential.
In this talk, the recent progress of our lab on study of non Watson-Crick structure recognition by
small molecules will be discussed. Different small organic molecules mimicking natural products
are designed to selectively bind to bulged structures. It has been found that those designed small
molecules not only bind to the non Watson-Crick structures, but also express different biological
functions through their selective binding. Neocarzinostatin analogues, which bind bulged structure
with micromolar of dissociation Kd, can stimulate the DNA slippage during its replication,
especially for those DNA sequences of triply repeats that cause certain genetic diseases.
Tylophorine B, which binds bulged structure of DNA and RNA with nanomolar of dissociation Kd,
interferes with Tobacco Mosaic Virus particle assembly to inhibit TMV virus infection.
Sparsomycin analogues targeting on ribosome inhibit bacterial growth. Through our work, we have
shown that study on non Watson-Crick structure recognition by small molecules is an efficient way
to generate bioactive molecular probes for understanding the molecular mechanism of some
important biological process involving such bulged structures in nucleic acids.
193

IL-45
PROBING MECHANISMS OF PHOSPHOTRANSFERASES WITH THIO EFFECTS
Karol Bruzik
Department of Medicinal Chemistry and Pharmacognosy, The University of Illinois at Chicago 833 S. Wood St.
Chicago, IL 60612, USA Email: kbruzik@uic.edu
194

IL-47
RNA INTERFERENCE: THE NEW PARADIGM OF DRUG DISCOVERY BASED ON
NATURE'S PHOSPHOROUS CHEMISTRY
Muthiah Manoharan
Drug Discovery Alnylam Pharmaceuticals Cambridge, USA
Email: mmanoharan@isisph.com
195

IL-49
SYNTHESIS AND BIOLOGICAL STUDIES OF G-QUADRUPLEX STABILIZERS
Lige Ren, Jing Huang, Boqiao Fu, Xiang Zhou*
College of Chemistry and Molecular Sciences, Wuhan University, Hubei, Wuhan, 430072, P. R. of China
Telomeres exist at the ends of eukaryotic chromosomes and can protect chromosome. [1] It is
known that telomeric repeats with the single-stranded G-rich overhang can be extended by telomerase.
[2] . Telomerase is active in most tumor cells and not in normal cells and could be good strategy for
antitumor drug design with high selectivity. It was reported that telomerase inhibition occurred via a
quadruplex-mediated mechanism because of G4 selectivity over duplex DNA affinity and
increasing potency for telomerase inhibition. [3] We shall report our synthesis of new families of
G-quadruplex Stabilizers and study their interaction with G-quadruplex DNA.
Reference
[1] T. R., Cech, Cell 2004, 116, 273
[2] E. H. Blackburn, Cell, 2001, 106, 661..
[3] T. M. Fletcher, Expert Opin.Ther. Targets, 2005, 9, 457
196

O-96
PERIFOSINE INHIBITS MULTIPLE SIGNALING PATHWAYS IN GLIAL PROGENITORS AND COOPERATES
WITH TEMOZOLOMIDE TO ARREST CELL PROLIFERATION IN GLIOMAS IN VIVO.
Alan H. Shih, Hiro Momota, Edward Nerio, Eric C Holland
Perifosine (Octadecyl-(N,N-dimethylpiperidino-4-yl)phosphate) is a novel akylphosphocholine
that has anti-neoplastic properties. Perifosine may act by altering cellular membrane composition
or inhibiting mitogenic signalling. Specifically, it can act as an oral Akt inhibitor which exerts a
marked cytotoxic effect on human tumor cell lines, and is currently being tested in several phase II
trials for treatment of major human cancers. However, the efficacy of perifosine in human gliomas
has not been established. As Akt is activated in 70% of human glioblastomas, we investigated the
impact of perifosine on glia in culture and on a mouse glioma model in vivo. Here we show that
perifosine strongly reduces phosphorylation levels of Akt and extracellular signal-regulated kinase
(Erk) 1/2, induces cell cycle arrest in G1 and G2, and causes dose-dependent growth inhibition of
mouse glial progenitors in which Akt and/or Ras-Erk 1/2 pathways are activated. Furthermore,
because temozolomide is a common oral alkylating agent used in the treatment of gliomas, we
investigated the effect of perifosine in combination with temozolomide. We observed an enhanced
effect when both were used in culture. With these results, we combined perifosine and
temozolomide as treatment of platelet-derived growth factor B–driven gliomas in mice. Animal
studies showed that perifosine and temozolomide combination therapy was more effective than
temozolomide treatment alone (P < 0.01). These results indicate that perifosine is an effective drug
in gliomas in which Akt and Ras-Erk 1/2 pathways are frequently activated, and may be a new
candidate for glioma treatment in the clinic.
197

O-97
A LOW-MOLECULAR PHOSPHINIC INHIBITOR OF LEUCINE AMINOPEPTIDASE
OF POTENTIAL MEDICAL SIGNIFICANCE
A.Mucha
Department of Bioorganic Chemistry, Faculty of Chemistry, Wrocław University of Technology, WybrzeŜe
Wyspiańskiego 27, 50-370 Wrocław, Poland
H-hPheψ[PO2HCH2]Phe-OH, a phosphinic dipeptide analogue has been demonstrated to be a
potent, competitive inhibitor of cytosolic leucine aminopeptidase (LAP, E.C.3.4.11.1), mimicking
the transition state of the reaction catalysed by the enzyme. Exhibiting Ki value of 66 nM (for the
mixture of four diastereomers) it has been ranked among the most potent inactivators of LAP
reported so far [1] .
Here, we summarize the development of the inhibitor together with its current study and
application achievements. Thus, novel results concerning the activity of the individual
diastereoisomers of H-hPheψ[PO2HCH2]Phe-OH towards LAP are given. High performance liquid
chromatography and capillary electrochromatography based on silica modified with a cinchona
alkaloid-derived chiral selector have been utilized to separate all four stereoisomers. Recently, the
compound has been also successfully employed to inhibit leucyl aminopeptidase of P. falciparum, a
potential target protease for the development of new antimalarials. Significant suppression of both
the enzyme activity and the growth of the pathogen in vitro as well as the parasite burden in vivo
have been evidenced.
Reference
[1] J. Grembecka, A. Mucha, T. Cierpicki, and P. Kafarski, J. Med. Chem., 46, 2641(2003).
198

O-98
MAPPING OF THE FUNCTIONAL PHOSPHATE GROUPS IN THE CATALYTIC CORE OF
DEOXYRIBOZYME 10-23
Barbara Nawrot*, Kinga Widera, Marzena Wojcik, Beata Rebowska, Wieslawa Goss, Wojciech J. Stec
Department of Bioorganic Chemistry, Centre of Molecular and Macromolecular Studies of the Polish Academy of
Sciences, Sienkiewicza 112, 90-363 Lodz, Poland
Phone: +48-42-6816970, Fax: +48-42-6815483, E-mail: bnawrot@bio.cbmm.lodz.pl
The RNA phosphodiester bond cleavage activity of a series of sixteen thio-deoxyribozymes
10-23, containing a P-stereorandom single phosphorothioate linkage in predetermined positions of
the catalytic core from P1 to P16, was evaluated under single turnover conditions in the presence of
either 3 mM magnesium or manganese ions. A metal-specificity switch approach permitted to
identify non-bridging phosphate oxygens (pro-RP or pro-SP) located at seven positions of the core
(P2, P4 and P9-13) involved in a direct coordination with a divalent metal ion(s). By contrast,
phosphorothioates at positions P3,6,7, and P14-16 displayed no functional relevance in the
deoxyribozyme-mediated catalysis. Interestingly, PS modifications at positions P1 or P8 enhanced
catalytic efficiency of the enzyme. Among the tested deoxyribozymes, thio-substitution at position
P5 had the largest deleterious effect on the catalytic rate in the presence of Mg 2+ and this was
reversed in the presence of Mn 2+ ions. Further experiments with thio-deoxyribozymes of
stereodefined P-chirality suggest direct involvement of both oxygens of the P5 phosphate and the
pro-RP-oxygen at P9 in the metal ion coordination. In addition, it was found that the oxygen atom at
C-6 of G6 contributes to binding of metal ion and this interaction is essential for the 10-23
deoxyribozyme catalytic activity.
The obtained data enabled us to propose a model for the metal binding site in the catalytic core of
deoxyribozyme 10-23. In this model, the plausible ligands for metal coordination are the pro-RP and
pro-SP oxygen atoms of the P5 phosphate and the pro-RP oxygen from position P9 as well as the
carbonyl oxygen of the guanosine unit at position 6 of the 10-23 catalytic core (Figure).
O
T 4
P5
O T
O
P
A5 O
pro-R P
O O
Mg 2+
O
pro-S P
O A
O
P
O
O
O
O
N
?
O
N N
G 6
NH
199
?
NH 2
pro-R P
O
O
O
P
O O A
O
P9
O
O T
T 8
A 9

O-100
THE AZA-Α-AMINOPHOSPHONATE MACROCYCLES AS POTENTIAL
SUPRAMOLCULAR HOSTS FOR METAL IONS AND BIOLOGICALLY
IMPORTANT MOLECULES
P.Mlynarz a , A.Rydzewska a , S.Sliwinska a , G.Schroeder b ,P.Kafarski a
a Department of Chemistry, Wroclaw University of Technology, 50- 370 Wroclaw, Poland.
b Faculty of Chemistry, A. Mickiewicz University, Grunwaldzka 6, 60-780 Poznan
The discovery of family of macrocyclic compounds was the milestone in chemistry. These
compounds have been recognized as supramolecular receptors for metal ions and many organic
molecules. Therefore, they were used for construction of selective sensors, model compounds
mimicking enzyme actions or transport through membranes, etc. On the other hand,
aminophosphonates were found to be good enzyme inhibitors and metal ion chelators used in many
branches of industry (e.g. agricultural, pharmaceutical and chemical) [1] . In this work we designed
and synthesized aza-aminophosphonate macrocycles 1 and 2 combining features of both
macrocyclic and aza-8-aminophosphonic entities and based on well described receptor 3 as skeleton
for amino acids [2] . The introduction four phosphonic groups placed into carefully tailored cavity
should result in the new synthetic receptors for biologically important molecules and metal ions and
thus may serve as metalloreceptors or contrast agents for MRI.
References
[1]. “Aminophosphinic and Aminophosphonic Acids. Chemistry and Biological Activity”, Eds. V. P. Kukhar and H. R.
Hudson , John Wiley & Sons LTD, Chichester, 2000.
[2]. J. Huang, Sh.-A. Li, D.-X. Yang, W.-Y. Sun and W.-X. Tang, Bioorg. Biomed. Chem. J.2004, 12, 529.
200

O-101
STUDIES ON THE CONDENSATION OF H-PHOSPHONATE MONOESTERS
WITH S-NUCLEOPHILES
Renata Hiresova and Jacek Stawinski*
Department of Organic Chemistry, Arrhenius Laboratory, Stockholm University,
S-10691 Stockholm, Sweden;
Oligonucleotide analogues containing modified internucleotide linkages are of the growing
interest as potential therapeutic agents 1 and tools in molecular biology for manipulation of RNA and
DNA 2 . Among these, oligonucleoside phosphorothioates 2-4 and phosphorodithioates 5 are
particularly attractive since they are isopolar and isosteric to their natural congeners.
Here we report our preliminary studies on the condensation of nucleoside H-phosphonate
monoesters with various thiols to produce a new type of H-phosphonate analogues, nucleoside
H-phosphonothioates, bearing sulfur atom in the bridging position at the phosphorus center. Via
oxidative transformations, the produced H-phosphonothioate derivatives can be converted into
various nucleotide analogues that are difficult accessible on other routes.
DMTO
Abbreviations:
C.A. = coupling agent
R = alkyl, nucleosidyl, cholesteryl
Thy = thymin-1-yl
O
O
O
P H
O
Thy
DMTO
R-SH
C.A.
References
1. Zon, G. Pharm. Res. 1988, 5, 539-549.
2. Eckstein, F.; Gish, G. TIBS 1989, 97-100.
3. Eckstein, F. Ann. Rev. Biochem. 1985, 54, 367-402.
4. Cosstick, R.; Vyle, J. S. Tetrahedron Lett. 1989, 30, 4693-4696.
5. Brill, W. K.-D.; Tang, J.-Y.; Ma, Y.-X.; Caruthers, M. H. J. Am. Chem. Soc. 1989, 111, 2321-2322.
O
O
O
P O
SR
DMTO
Thy
201
[O]
O
O
O
P H
SR
Thy
[S]
DMTO
O
O
O
P S
SR
Thy

O-103
ESI INVESTIGATION OF NON –COVALENT COMPLEXES BETWEEN
PHOSPHORYLATED DAIDZEIN AND INSULIN
Chen Xiaolan 1 , Shi Xiaona 1 , Yuan Jinwei 1 , Lu Jiansha 1 , Qu Lingbo 1, 2 , Zhao Yufen 1,3
1
Department of Chemistry, Zhengzhou University, Zhengzhou, 450052, P. R. China
2
Anyang Normal College, Henan Province, Anyang, 455002, P. R. China
3
The Key Laboratory for Bioorganic Phosphorus Chemistry, Department of Chemistry
School Life Sciences and Engineering, Tsinghua University, Beijing, 10084, P. R. China
Since the end of last century, ESI-MS has begun to be used to reveal the existence of
non-covalent complexes, providing important stoichiometric information. Many researchers have
reported the use of ESI-MS to determine dissociation constants of such complexes. Gas phase
dissociation constants measured in this way have been found to correlate well with those measured
by solution based techniques [1,2] . In the work described in this paper, daidzein
(7,4′-dihydroxyisoflavone) was first phosphorylated by a modified Atherton-Todd reaction and the
structures of the five target products were determined by X-ray, IR, NMR and ESI. Our ESI results
show that all the phosphorylated daidzeins can form non-covalent complexes with the protein
insulin, while non-covalent complexes were not detected in solutions of unphosphorylated daidzein
and insulin. The relative affinity of each non-covalent complex was obtained according to its
different decomposed orifice voltage. From Table 1, it is clear that compound e has the highest
disappeared orifice voltage and therefore the strongest binding affinity. The relative stability of the
non-covalent complexes was closely associated with the length of the hydrophobic chain.
HO
O
O
OH
O
RO PH
OR
CCl4,Et3N
DMF
202
RO
O
P O
OR
a R= -CH3 b R= -CH2CH3 c R= -CH2CH2CH3
d R= -CH(CH3)2 e R= -CH2CH2CH2CH3
Scheme 1.
Table 1. The orifice voltage of the non- covalent complexes disappeared
Compound a b c d e
orifice voltage /Volt 133.8 146.0 151.8 157.4 162.9
References
[1] Daniel, J.M.; McCombie, G.; Wendt, S. J. Am. Soc.Mass Spectrom. 2003,14,442.
[2] Dotsikas, Y.; Loukas, Y.L. J. Am. Soc. Mass Spectrom. 2003,14,1123.
O
O
OH

O-104
SYNTHESIS OF NOVEL STEROIDAL BIOCONJUGATES WITH AZT
AND PHOSPHORUS
Peiyuan Jin, Kai Liu, Yong Ju,*
Yufen Zhao
Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology, Ministry of Education, Department of
Chemistry, Tsinghua University, Beijing 100084, P. R. China
Steroidal phosphates are important biological molecules.1 3’-Azido-3’-deoxythymidine (AZT,
Zidovudine) is now the backbone of most combination therapies for AIDS and HIV infection, and it
remains one of the most prescribed AIDS drugs. AZT is activated by phosphorylation in vivo and
inhibits HIV replication by blocking a critical HIV enzyme,2 and many H-phosphonates of AZT
have also been shown to possess high anti-HIV activity.3 In order to further improve the activity
and overcome the drawback, some steroid phospholipids conjugated with AZT were synthesized in
good yields as potential membrane-soluble prodrugs of the phosphate forms,4, 5 which is due to
their lipophilic characteristic, lymphocyte membrane affinity and the ability of binding to low
density lipoprotein. These phospholipids were easily transformed to corresponding phosphates,
phosphorothioates, and phosphoroselenoates or phosphoramidates6, 7 by oxidation or conjugation
with amines using Atherton–Todd reaction. The structures of synthesized steroidal conjugates with
AZT containing phosporus were confirmed on the basis of the 1H NMR, 31P NMR, and ESI-MS
data.
PhO
O
P OPh
(1) AZT,Py
(2) ROH, Py
O
RO P O
H H
ROH =
O
N 3
O
O
N
203
NH
HO
HO HO
O
H
P O
n O
n = 14; 16
N 3
O
R'OH =
O
N
HO
NH
O
+ H2N O
RO
O
P O
X- Et3NH +
X: a = S; b = Se; c = O N3 O
O
H H
O N N P O
R'' R' R' R''
N O
O
H
O
O
*
N3 n
R'' = CH2CH2 CH2CH2CH2CH2CH2CH2 CH2CH2NHCH2CH2 CH2CH2CH2NHCH2CH2CH2 Project supported by the NSF of China (No. 20542004) and SRFDP of Higher Education (No.20050003104).
References
1. Sprecher, M.; Breslow, R.; Philosof-Oppenheimer, R.;Chavet, E. Tetrahedron 1999, 55, 5465.
2. Yarnell, A. Chem. Eng. News 2005, 83, 48.
3. Cardona, V. M. F.; Ayi, A. I.; Aubertin, A. M.; Guedj, R. Antiviral Res. 1999, 42, 189.
4. Ji, S. H.; Xiao, Q.; Ju, Y.; Zhao, Y. F. Chem. Lett. 2005, 34, 944.
5. Xiao, Q.; Sun, J.; Ju, Y.; Zhao, Y. F.; Cui, Y. X. Chem. Lett. 2003, 32, 522.
6. Ji, C. J.; Xue, C. B.; Zeng, J. N.; Zhao, Y. F. Synthesis 1988, 444.
[O]
O
O
O
O
N
NH
O
N
O
NH
O

P-33
THE CHEMICAL SYNTHESIS OF OLIGONUCLEOTIDE PHOSPHORAMIDATES
HongYu Zhang, ChunJian Duan, XiangQian Liu, XiaoLan Chen, LingBo Qu, YuFen Zhao
Key Laboratory of Chemical Biology and Organic Chemistry, Zhengzhou University, Zhengzhou 450052
The method of synthesis of monofunctional nucleoside phosphoramidity by using trivalent
phosphorous as reactant has been drawn much attention since the approach was introduced by
Beaucage and Caruthers. All chemotherapeutic nucleoside analogues, for viral infections and cancer,
exert their effect only after metabolic activation in the target cell to their 5’-phosphate forms. Often
the efficiency of intracellular phosphorylation of nucleoside analogues can limit their therapeutic
potential, but the pre-formed phosphates are of limited utility on account of their poor membrane
permeation. In order to research it function, these oligonucleotide phosphoramidates were
synthesized. All compounds have been elucidated by 1 H NMR, 13 C NMR, MS.
HN
O
HO
O
O
N
H H
H
OH
H
OH
R 1
HO
H
H
O
O
HN
O
O
N
H
H
O
R 1
Cl
P
Cl
PCl3 HN
O
O
H
H
O
DMTrO
O
O
N
H H
H
OH
H
OTBDMS
Scheme 1
References
1. Christopher M., Jean-Christophe T., Felice D.,etc., Bioorganic & Medicinal Chemistry. 2005, 13, 3219–3227.
2. Joshua S. W., David K., Stephen A.S.. etc. Nucleic Acids Research, 2004, 4(32), 1502-1511.
O
O
204
HN
O
N
H
H
O
R 1
R 3 OOC
R 1 =H,Br, R 2 =H,CH 3, R 3 =CH 3,CH 2CH 3
R 1
R 2
DMTrO
O
H H
R
H
O
O
P
H
OTBDMS
O
N
H H
O
H
H
O
H
O
2
R3 O N
OOC
NH 2
HN
O
R 1

P-41
STUDIES ON THE SELF-ASSEMBLY OF L-SERINE INTO L-SERINE
PHOSPHOPEPTIDE MEDIATED BY PHOSPHORUS OXYCHLORIDE
Jianchen Zhang 1 , Wenping Shi 1 , Jun Xu 2 , Yufen Zhao 3
1
Department of Chemical Defense, Institute of Chemical Defense, Beijing 102205
2
Department of Humanities and Basic Sciences, Zhengzhou College of Animal Husbandry Engineering, zhengzhou
450011
3
The Key Laboratory for Chemical Biology of Fujian Province, Department of Chemistry, University, Xiamen 361005
L-Serine phosphopeptide is a main bioactive segment in casein Phosphopeptides. In this paper,
L-Serine peptide was synthesized by the self-assembly of L-serine mediated by phosphorus
oxychloride. 31 P NMR and ESI-MS/MS were used to study the mechanism and products of the
reaction and confirm the structures of the peptides.
The reaction of L-serine and phosphorus oxychloride could be assembled into 2~8 homo-peptides
by phosphorus oxychloride activation, after quenching with water, the reaction mixture yielded the
L-Serine peptide, which were analyzed by ESI-MS and ESI-MS/MS. It was found that the length
and yield of L-Serine peptide were related with the reaction time, the polarity of the solvent and the
reaction temperature. As the reaction time was prolonged, the length of peptides increased; the
lengths of peptides increased as increased the polarity of the solvent. Especially, acetonitrile or
chloroform could give the better result; Lower temperature might close down the reactive of
hydroxy and increase yield. Actually, L-Serine peptide libraries were obtained. The quantitative
water was added to the reaction mixture. The temperature was controlled at 60 ℃ and kept stirring
for 2.0 h. After cooling, 95% ethanol was added and stored overnight at 3 ℃ . And L-Serine
phosphopeptide was obtained.
References
Fowshon A. M., Maeda M., Sasaki S., Bioorg. Med. Chem., 2000, 8, 465-473
Liu Y., Fan H.K., Zhou H. et al., Chem. J. Chin. University, 1999,20, 744-746
Qi J.,Fang R.,Zhou H. et al., Chem. J. Chin. University, 1996, 17, 1738-1741
Kui Lu, Yan Liu, Ning Zhou, Yu-Ping Feng, Li Xu, Ling-Bo Qu, Yu-Fen Zhao, J.Tsinghua University, 2001, 41, 80-82
Kui Lu, Yan Liu, Yi Chen, Ning Zhou, Qiang Lu, Ling-Bo Qu, Yu-Fen Zhao, J Tsinghua University, 2001, 41, 77-79
Kui Lu, Ning Zhou, Yan Liu, Yi Chen, Xiang-Fen Guo, Ling-Bo Qu, Yu-Fen Zhao, J. Tsinghua University, 2001, 41,
87-89
205

P-43
SYNTHESIS OF N-PROTECTED O-HYDROXYL-PHENYL -
α-AMINOPHOSPHONIC MONOESTER
Jianfeng Zhang, Zhiwei Miao, Zhanwei Cui and Ruyu Chen
(State Key Laboratory of Elemento-Organic Chemistry, Research Institute of Elemento-Organic
Chemistry, Nankai University, Tianjin 300071, China)
α-Aminophosphonic and phosphinic acids are the phosphorous analogues of α-aminocarboxylic
acids, and therefore have biological importance both in themselves and as building blocks for
peptides [1] . They have acquired great attention in synthetic organic chemistry and a number of
synthetic methods have been developed during past two decades. Of these methods, nucleophilic
addition of phosphites to imines catalyzed by a base or an acid is the most convenient one. A
variety of metal halides such as TiCl4 [2] , InCl3 [3] , TaCl5-SiO2 [4] , Mg(ClO4)2 [5] have been used as
Lewis catalysts in methylene chloride or other organic solvent to promote this addition. To avoid
these disadvantages of the use of organic solvents, a couple of modifications using montmorillonite
clay [6] and alumina [7] in dry media under microwave irradiation have been reported. In 2002, Ranu [8]
reported a more practical green alterative for the synthesis of α-aminophosphonates by a
three-component condensation of carbonyl compounds (aldehydes and ketones), amines and diethyl
phosphite at 75–80°C in neat without any solvent and catalyst. We would like to disclose a practical
and green method for the synthesis of N-protected o-hydroxyl-phenyl-α-aminophosphonic
monoester (Scheme 1).
O
H3CH2CO P
H3CH2CO 1
O
NH + +
2
Cl
R1 R2 2
O
P
O
3
no catalyst
solvent-free, r.t.
Scheme 1
H2O O
H3CH2CO H
P N
H3CH2CO R1 4
HO
O
P O
OH
R2
4 R1 R2
Yield (%)
Tab. 1
4 R1 R2
Yield (%)
4a p-Cl-C6H5 H 80 4f p-CH3O-C6H5 H 90
4b o-Cl-C6H5 H 92 4g p-NO2-C6H5 H 93
4c p-Br-C6H5 H 89 4h (CH2)5 84
4d o-Br-C6H5 H 85 4i CH3 CH3 87
4e C6H5 H 91
Reference
[1] Kukhar, V. P.; Hudson, H. R. Aminophonic and Aminophinic Acids Chemistry and Biological Activity. John
206

P-44
A NOVEL MECHANISM ABOUT THE CLEAVGE OF N-GLYCOSIDIC BOND IN
ELECTROSPRAY IONIZATION TANDEM MASS SPECTRA OF NUCLEOTIDE
Jihong Liu 1 , Shuxiao Cao 1 , Ruyi Zou 1 , Jiansha Lu 1 , Xincheng Liao 1 , Yufen Zhao 1,2*
3. Key Laboratory of Chemical Biology and Organic Chemistry, Department of Chemistry, Zhengzhou University,
Zhengzhou, 450052, P.R.China
4. Key Laboratory for Bioorganic Phosphorus Chemistry of Ministry of Education, Department of Chemistry School
of Life Sciences and Engineering, Tsinghua University, Beijing 100084, P.R.China
ESI-MS/MS has become an important analytical tool for the analysis of nucleotide 、
oligonucleotide and their derivatives 1 . Nucleotides are the basic unit of nucleic acid, so its
fragmentation pathways in electrospray ionization tandem mass spectra will give some implication
on the analysis of oligonucleotide using ESI-MS/MS. Nucleotides often gives the fragment
originated from the cleavage of the N-glycosidic bond, and this cleavage was expressed that a new
double bond generated in the sugar moiety 2,3 . However, when we used deuterium to substitute
active hydrogene of nucleotide and study it by ESI mass spectrometry, we presented a new
mechanism about the cleavge of the N-glycosidic bond. Instead of generating a double bond in
sugar moiety, the novel mechanism is 5’-,3’-nucleotides produced cycle ions shown as figure1.
Table 1 the ions of deuterated and non-deuterated nucleotides
Sample name Precursor ions Fragment ions (M-Base)
5’- or 3’- Nucleotide [Nucleotide-H] - 211
Deuterium-labeled nucleotide [Deuterium-labeled nucleotide –H] - 213
B
O
O
H H
H H
OD OD
P
DO O
O- B
DO
H
O
H
H
O
H
OD
O
P O
OD
-
O
P
O
D
O O
O
H H
H
OD
H
OD
DO
H
O H
H
H
O OD
O
O
P
O D
207
B -
BD
B -
BD
-O O
P
O O
O
H H
H H
OD OD
DO
H
O H
H
H
O OD
O
O
P
- O
Figure1 Proposed mechanism of the N-glycosidic bond cleavge
Refference
1.E. Nordhoff,F. Kirpekar. P. Roepstorff. Mass spectrometry Reviews, 1996, 15,67-138
2.Petr Fryčák,Renata Hušková,Tomáš Adam etc.J. Mass Spectrom. 2002, 37:1242-1248
3.Hongxia Liu,Canfang Zhao,Jiansha Lu etc. Analytica Chimica Acta, 2006, 566:99-108

P-45
SYNTHESIS OF ISOPRENOID OLEFIN ISOMERS VIA PHOSPHONIUM AND
PHOSPHORYL STABILIZED CARBANIONS
José S. Yu and David F. Wiemer
Department of Chemistry, University of Iowa, Iowa City, IA 52242, USA
Correspondence to: david-wiemer@uiowa.edu
To provide tools for studies of isoprene metabolism, the complete set of four farnesol
stereoisomers (1-4) and a pair of geranylgeraniol isomers (5 and 6) have been synthesized using a
variety of modified Wittig and Horner-Wadsworth-Emmons (HWE) reactions. The central issue in
the synthesis of the (2Z)-trisubstituted alcohols 2, 3, and 6 was the formation of the (Z)-allylic
alcohol. Past examples provided precedent for use of a modified Wittig reaction that involved a
-oxido ylide derived from an aldehyde in the construction of disubstituted (Z)-allylic alcohols.
This strategy was extended to -oxido ylides derived from the unsymmetrical ketones geranylacetone,
nerylacetone or (5E,9E)-farnesylacetone to achieve the desired substitution pattern with good olefin
stereoselectivity (Org. Lett. 2005, 7, 4803-4806). Use of the same set of ketones in modified
HWE reactions, including the Still-Gennari and Ando strategies, provided the corresponding
(Z)-α,β-unsaturated esters and these esters could be reduced to the (Z)-allylic alcohols. However,
this approach afforded lower (Z)-selectivity than obtained through the -oxido ylides. In contrast,
preparation of the isoprenoids 1, 4, and 5 was based on a classical HWE condensation with the
same set of starting ketones, and afforded the desired (2E)-isomers with good stereocontrol. Both
the (2Z)- and (2E)-isoprenoid alcohols were converted to the respective bisphosphonates and/or
-hydroxyphosphonates for further biological studies.
OH
OH
OH
(2E,6E)-farnesol (1) (2Z,6E)-farnesol (2) (2Z,6Z)-farnesol (3) (2E,6Z)-farnesol (4) OH
OH
(2E,6E,10E)-geranylgeraniol (5) (2Z,6E,10E)-geranylgeraniol (6) OH
208

P-52
INVESTIGATION ON INTERACTION OF L-METHIONINE DIPEPTIDE WITH CT-DNA
BY ULTRAVIOLET SPECTROSCOPY METHOD
Kui Lu* 1 ,Rui Li 1 ,Li Ma 1 ,Yufen Zhao 2
1.School of Chemistry and Chemical Engineering, Henan University of Technology, Zhengzhou 450052, China;
2.Department of Chemistry, Xiamen University, Xiamen 361005, China
Phosphorus plays an important role in the origin of life and regulate and control of life, our
investigative group have study the peptide formation reactions with the assistance of
abio-phosphorous compound [1] .In this paper, we let the same mol POCl3 and L-methionine react in
the presence of tetrahydrofuran as solvent, produce more short-chain polypeptides through control
the reaction conditions and finally get the L-methionine dipeptide by HPLC. The product's structure
has been characterized by the means of 1H-NMR, 13C-NMR and ESI-MS. Because Several small
molecules have been shown to interact with DNA at the molecular level by specific binding modes.
These binding studies were driven partly by the need to understand the mechanism of anticancer
drug action [2] , to decipher the chemical basis for the carcinogenicity of environmental pollutants and
toxic chemicals [3] and to serve as analogues in studies of protein-nucleic acid recognition [4] . The
interaction of L-methionine dipeptide with ct-DNA was studied by ultraviolet spectra. The results
showed that L-methionine dipeptide could interact with phosphorous groups of ct-DNA which
would affect the conformation of ct-DNA (Fig 1). In general, the longer the time of interaction of
L-methionine dipeptide with ct-DNA was, the more bovious the hypochromic effect became. In
addition, the influences of concentration, phosphateion and pH values on the interaction of
L-methionine dipeptide and ct-DNA were also investigated.
Acknowledgements: The authors would like to thank the financial supports from the Chinese
National Science Foundation (No.20272055, 20572016), Henan Province Science Foundation for
Prominent Youth (No.0312000900) and Office of Education of Henan Province (No.
2006KYCX017, 200510459015).
209

References:
[1] Lu, K.; Liu, Y.; Zhou, N.; Chen, Y.; Feng, Y.-P. ; Guo, X.-F.; Chen, W.; Qu, L.-B.; Zhao, Y.-F. Acta Chim. Sinica
2002, 60, 372 (in Chinese)
[2] M.J. Waring, in: G.C.K. Roberts (Ed.), Drug Action at the Molecular Level, Macmillan, London, 1977, p. 167
[3] M.A. Warpehoskj, L.H. Hurley, Chem. Res. Toxicol. 1 (1988) 313
[4] D. Porschke, in: W. Guschlballer, W. Saenger (Eds.) DNA–Ligand Interactions Specificity and Dynamics of
Protein–Nucleic Acid Interactions, Plenum, New York, 1986, p. 85
210

P-61
REMINERALIZATION EFFECTS OF HONEYSUCKLE FLOWER SOLUTION ON
INITIAL ENAMEL CARIOUS LESIONS IN VITRO
Linglin Zhang
As we have known, 96 percent of dental enamel is the chemical substance of inorgance.
Hydrosyapatite is the elemental structure units of enamel. Enamel also contains octacalcium
phosphate, calcium phosphate dihydrate, dicalcium phosphate anhydrous, tricalcium phosphate, and
amorphous calcium phosphate. In oral cavity, the process of enamel demineralization and
remineralization is alterative. During this period, if demineralization plays predominant role, it will
result in carious lesions on the enamel surface. on the other hand, if remineralization plays
predominant role as a result of artifical method, initial carious lesions will be restored. In this
experiment, the effects of Honeysuckle Flower on remineralization of initial enamel carious lesions
were studied in vitro. This helps to make Honeysuckle Folwer as some kinds of natural anticarious
drugs to treat the initial enamel cavious lesions.
The labial enamel from crowns of the newly extracted fresh bovine incisors were made into
enamel blocks in the same size. Then they were grounded and polished. Those blocks without
calculus, pigments, lisions, fluoxic cachexia and cracks were chosen to be dipped in acid solution of
PH 4.5. After 72 hours, the artificial early lesions emerged on the surface of labial enamel. Next, 30
blocks of them with suface microhardness between 311.00 kHN and 315.00kHN entered the phae of
remineralization.
Using 50 g/L Honeysuckle Flower(group 1),1 g/L NaF(group 2) and deionized water(group 3) in
the first step of PH-cycling respectively, 30 blocks were randomly divided into three groups. After
12 times of pH-cycling, microhardness of enamel surface was measured on the labial enamel blocks,
and the recovery percentage of it (% SMHR) was calculated.With X-ray EDS, weight percentage of
Ca and P on the surface of remineralized enamel was measured. The morphology of remineralized
enamel was observed by polarizing microscope. The result showed that microhardness of enamel
surface in group 1and 2 increased obviously. Weight percentage ratio of Ca and P on the surface of
enamel in group 3 was much less than the other two groups. The density of lesioned layer on the
surface in group 1and 2 grew heavily obviously, and the thickness of it lessened. It can be
concluded that Honeysuckle Flower can promote the remineralization of initial enamel carious
lesions, so it can become a kind of new natural anticarious medicine.
211

P-72
SELF-ASSEMBLY OF L-GLUTAMINE INTO OLIGO-PEPTIDES MEDIATED BY
PHOSPHRORIC CHLORIDE
Li Ma, Ming-xiu Lü, Wei-na Cao, Kui Lu*
School of Chemistry and Chemical Engineering, Henan University of Technology, Zhengzhou 450052, China
Oligopeptides can act as drug or precursor of drug because of their strong bioactivity, which has
gained significant attraction. Therefore, the synthesis of peptides became a research focus of
organic synthesis [1] . Even though there are lots of papers about peptide synthesis related to the
chemical evolution of life, there is litter investigation on the intrinsic relationship between the
phosphorus and amino acids [2] .
In this paper, the self-assembly reactions of L-glutamine with phosphroric chloride were studied
by using electrospray ionization mass spectrometry (ESI-MS). On quenching with water, the
reaction mixtures, which were produced under different reaction conditions, yielded the
corresponding peptides. Influence of the reaction conditions such as reaction time, solvent, and
temperature on self-assembly into oligo-peptides for L-glutamine were monitored. The reactions are
shown in scheme 1.
H
H
N
O
H
C C
CH 2
CH 2
C
NH 2
O
OH
PCl 5
Scheme 1 Self-assembly of L-glutamine into oligo-peptides mediated by phosphroric chloride
In conclusion, the proper condition of direct synthesis was reaction time of 4h, in the solvent of
acetonitrile and temperature of 50 ℃ . A series of mass peaks corresponding to oligo-peptides
of
L-Gln were observed by electrospray ionization mass spectrometry (ESI-MS). The dipeptide
(m/z=275) and the cyclotripeptide (m/z=385) were the main compounds in the reaction mixtures.
Acknowledgements
The authors would like to thank the financial supports from the Chinese National Science
Foundation (No.20272055, 20572016), Henan Province Science Foundation for Prominent Youth
(No.0312000900) and Office of Education of Henan Province (No. 2006KYCX017).
References
[1] N. Zhou, K. Lu, Y. Liu, Y. Chen, G. Tang, S.-X. Cao, L.-B. Qu, Y.-F. Zhao. Rapid Commun Mass Sp 2002,16 (8):
790
[2] N. Zhou, K. Lu, Y. Liu, et al, The abstracts of the 13 th international conference on the origin of life, 2002, P87
212
H 2O
H
H
N
O
H
C C OH
n
CH 2
CH 2
C
NH 2
O

P-74
SYNTHESIS AND BIOLOGICAL ACTIVITY OF α-HYDROXYPHOSPHONATES
Na Zuo and Hong-Wu He*
Key Laboratory of Pesticide and Chemical Biology of Ministry of Education
College of Chemistry Central China Normal University, Wuhan 430079, P. R. China
Several α- hydroxyphosphonates have been prepared by the Pudovik reaction. 5,5- dimethyl -4phenyl
-1,3,2- dioxaphosphinan -2- one reacts with aldehyde to form the title compounds in good
yields(80-90%). Triethylamine is added as catalyst .The best reaction time is 2-3 hours and the
temperature is 25℃. All 10 of compounds were confirmed by 1 HNMR, IR and element analysis,
and one was examined by the single crystal X-ray diffraction. The results of preliminary bioassay
indicated that the title compounds exhibited a certain herbicidal activities.
CHO + PhCHO
PCl3
EtOH
Ph
2
O O
PH
O
213
Ph
KOH
OH
EtOH OH
RCHO
Et3N Ph
R= alkyl, Ph, substituted Ph, Furyl
1
HO
O R
O P
O
Acknowledgments
Financial support by National Basic Research Program of China (2003CB114400) and NNSFof
China ( 20372023)
REFERENCES
Meier, C. Angew. Chem. Int. Ed. Engl. 35, 70 (1996)
Shi, D. Q.; Wei, J. and Tan, X. S., Chin. J. Org. Chem. 12, 1602 (2005)
He, H. W.; Wang, T. and Yuan, J. L. J. Organomet. Chem. 690, 2608 (2005)
Sudha K.; Senthamizh S. R. and Kumara S. K. C. Synthesis. 2, 207(1997)
3

P-85
BIO-RELEVANT DERIVATIVES OF CALIXARENE PHOSPHONIC ACIDS
S.Cherenok a , A.Vovk b , I.Muravyova b , A.Marcinowicz c , J.Poznanski c , O. Muzychka b , V.Kukhar b , W.Zielenkiewicz c ,
V.Kalchenko a
a Institute of Organic Chemistry, NAS of Ukraine, 02660, Kyiv-94, Ukraine
b Institute of Bioorganic Chemistry and Petrochemistry, NAS of Ukraine, 02660, Kyiv-94, Ukraine
c Institute of Physical Chemistry, Polish Academy of Sciences, 01-224, Warsaw, Poland
Calixarenes endowed with aminoacid or peptide units demonstrate a high bio-activity [1]. Within
the project we have synthesized and investigated a series of the cone-shaped calix[4]arenes
functionalysed at the macrocyclic upper rim with bio-relevant α- hydroxyphosphonic or
α-aminophosphonic or methylenebisphosphonic acid groups [2-4].
Complexation of calix[4]arene bis-α-hydroxyphosphonic acids (Racemic or Meso forms) with a
series of natural amino acids and dipeptides was investigated by calorimetry, NMR and molecular
modelling methods [3]. The association constants of the host-guest complexes in methanol (up to
45000 M-1) were determined. Hydrophobic, electrostatic, N-H-π, C-H-π interactions in the
host-guest complexes are discussed.
Calix[4]arenes grafted with the α-hydroxyphosphonic or α-aminophosphonic or
methylene-bis-phosphonic acid groups significantly overcome modelling acyclic phosphonic acids
in inhibition of bovine intestinal and porcine kidney alkaline phosphatases [2, 4]. In Tris-HCl buffer
(pH 9) the (R,R) diastereomer of calixarene bis-α-aminophosphonic acid demonstrates 50 fold
higher potency than the (S,S) diastereomer [4].
References:
[1] A.Casnati, F. Sansone, R.Ungaro. Acc. Chem. Res. 2003. 36. 246-254.
[2] A.I. Vovk, V.I. Kalchenko, S.O. Cherenok, V.P. Kukhar, O.V. Muzychka, M.O. Lozynsky. Org. Biomol. Chem.
2004. 2. 3162-3166.
[3] W. Zielenkiewicz, A. Marcinowicz, S. Cherenok, V. Kalchenko, J. Poznański. Supramolecular Chemistry. 2006. 18.
167-176.
[4] S. Cherenok, A.Vovk, I. Muravyova, A. Shivanyuk, V. Kukhar, J. Lipkowski, V. Kalchenko. Organic Letters. 2006.
8. 549-552.
214

P-123
EFFECTS OF PHOSPHORYLATION ON THE CONFORMATION
OF PEPTIDE AND PROTEIN
Yan-Mei Li, Yu-Fen Zhao
Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Department of
Chemistry, Tsinghua University, Beijing 100084
The regulation of biochemical activity by protein post-translational modifications is a pervasive
cellular control mechanism. Protein phosphorylation is a key posttranslational modification
mechanism controlling the conformation and activity of many proteins. Through the use of
phosphorylation cycles and cascades, the cell is able to regulate a diverse set of processes, including
cellular movement, reproduction and metabolism. It is the simplicity, reversibility and flexibility of
phosphorylation that explains why it has been adopted as the most general control mechanism of the
cell. The use of the phosphorylation/dephosphorylation of a protein as a control mechanism has
many advantages: rapid, taking as little as a few seconds, no require new proteins to be made or
degraded and easily reversible.
With regard to its regulatory mechanism, it is of fundamental importance to study the role and
function in protein networks by phosphorylation. Increasing evidence has implicated an essential
role of phosphorylation by activating α-COOH to form amide bond in peptide synthesis, increasing
the cis content of the peptidyl-propyl amide bond, causing local structure more ordered, regulating
intrisically disorder domain, and effecting the protein distribution in cell. Phosphate acts as the
molecular switch to modulate protein networks.
Reference
[1] Chen YX, Du JT, Zhou LX, Li YM*, et al. Alternative O-GlcNAcylation/ O-Phosphorylation of Ser16 Induce
Different Conformational Disturbances to the NTesrminus of Murine Estrogen Receptor β. Chem. Biol. 2006, 13:
937-944.
[2] Du JT, Li YM*, Wei W, et al. Low Barrier Hydrogen Bond Between Phosphate and Amide Group in Phosphopeptide.
J. Am. Chem. Soc. 2005, 127: 16350-16351.
[3] Du JT, Li YM*, Ma QF, et al. Synthesis and Conformational Properties of Phosphopeptides Related to the Human
Tau Protein. Regul. Pept. 2005, 130: 48-56.
[4] Schlummer S, Vetter R, Kuder N, Chen YX, Li YM, et al. Influence of Serine O-Glycosylation or O-Phoshorylation
Close to the vJun Nuclear Localisation Sequence on Nuclear Import. ChemBioChem 2006, 7: 88-97.
[5] Chen ZZ, Tan B, Li YM*, et al. Activity Difference between α-COOH and β-COOH in N-Phosphoryl Aspartic Acids.
J. Org. Chem. 2003, 68: 4052-4058.
[6] Chen ZZ, Li YM*, Wang HY, et al. Theoretical Study on the Rearrangement of β-OH and γ-OH in ESI Mass
Spectrometry by N-phosphorylation. J. Phys. Chem. A 2004, 108: 7686-7690.
215

P-124
SYNTHESIS AND PURIFICATION OF L-HYDROXYPROLINE OLIGO-PEPTIDES
ASSISTED BY PHOSPHORUS OXYCHLORIDE
Yan-ting Sun, Ye-zhen Feng, Kui Lu*
School of Chemistry and Chemical Engineering, Henan University of Technology, Zhengzhou 450052, China
We have demonstrated that α-amino acids could be assembled into oligo-peptides with the
assistance of inorganic phosphorus [1] . Similar results were obtained in the reaction of
L-Hydroxyproline(L-Hypo) and phosphorus oxychloride. To find the best experimental condition,
the solvent, reaction time, reaction temperature, the molar ratio of L-Hypo and POCl3 were
examined. The results obtained suggested that the proper condition of direct synthesis was the
molar ratio of L-Hypo and POCl3 of 1 to 1, reaction temperature of 20 ℃ , reaction time of 2h and in
acetonitrile as solvent. A series of mass peaks corresponding to oligo-peptides of L-Hypo were
observed by electrospray ionization mass spectrometry (ESI-MS) and multistage electrospray
ionization mass spectrometry (ESI-MS/MS).The dipeptide Hypo-Hypo (m/z=245), tripeptide
Hypo-Hypo-Hypo(m/z=358), as well as cyclo-dipeptide cyclo-Hypo-Hypo (m/z=227) were purified
by reversed phase high-performance liquid chromatography(RPLC). This approach may provide a
sound basis for developing new technologies of peptides synthesis of practical use.
Figure 1 RPLC of the reaction mixtures
This work was financial supported by National Nature Science Foundation of China
(No.20272055, 20572016) , Henan Province Science Foundation for Prominent Youth
(No.0312000900) and Office of Education of Henan Province (No. 2006KYCX017).
References
[1] Lu, K.; Liu, Y.; Zhou, N.; Chen, Y.; Feng, Y.-P. ; Guo, X.-F.; Chen, W.; Qu, L.-B.; Zhao, Y.-F. Acta Chim. Sinica
2002,60,372 (in Chinese).
216

P-125
SELF-ASSEMBLY OF L-GLUTAMINE INTO OLIGO-PEPTIDES MEDIATED BY
PHOSPHRORIC CHLORIDE
Li Ma, Ming-xiu Lü, Wei-na Cao, Kui Lu*
School of Chemistry and Chemical Engineering, Henan University of Technology, Zhengzhou 450052, China
Oligopeptides can act as drug or precursor of drug because of their strong bioactivity, which has
gained significant attraction. Therefore, the synthesis of peptides became a research focus of
organic synthesis [1] . Even though there are lots of papers about peptide synthesis related to the
chemical evolution of life, there is litter investigation on the intrinsic relationship between the
phosphorus and amino acids [2] .
In this paper, the self-assembly reactions of L-glutamine with phosphroric chloride were studied
by using electrospray ionization mass spectrometry (ESI-MS). On quenching with water, the
reaction mixtures, which were produced under different reaction conditions, yielded the
corresponding peptides. Influence of the reaction conditions such as reaction time, solvent, and
temperature on self-assembly into oligo-peptides for L-glutamine were monitored. The reactions are
shown in scheme 1.
H
H
N
O
H
C C
CH 2
CH 2
C
NH 2
O
OH
PCl 5
Scheme 1 Self-assembly of L-glutamine into oligo-peptides mediated by phosphroric chloride
In conclusion, the proper condition of direct synthesis was reaction time of 4h, in the solvent of
acetonitrile and temperature of 50 ℃ . A series of mass peaks corresponding to oligo-peptides
of
L-Gln were observed by electrospray ionization mass spectrometry (ESI-MS). The dipeptide
(m/z=275) and the cyclotripeptide (m/z=385) were the main compounds in the reaction mixtures.
Acknowledgements: The authors would like to thank the financial supports from the Chinese
National Science Foundation (No.20272055, 20572016), Henan Province Science Foundation for
Prominent Youth (No.0312000900) and Office of Education of Henan Province (No.
2006KYCX017).
References:
[1] N. Zhou, K. Lu, Y. Liu, Y. Chen, G. Tang, S.-X. Cao, L.-B. Qu, Y.-F. Zhao. Rapid Commun Mass Sp 2002,16 (8):
790
[2] N. Zhou, K. Lu, Y. Liu, et al, The abstracts of the 13 th international conference on the origin of life, 2002, P87
H 2O
217
H
H
N
O
H
C C
CH 2
CH 2
C
NH 2
O
OH
n

P-135
DESIGN AND SYNTHESIS OF 5’-FLUORESCENTLY LABELED NUCLEOSIDES
Zheng Jinyun*; Zhang Shufeng,Zhao Yufen
Department of chemistry, Zhengzhou university, Zhengzhou, 450052 P.R. China
The application of fluorescence methods to macromolecules study has been a dramatic surge in
the last few years by providing useful information concerning structure, distance, orientation,
complexation and location of biomolecules. Fluorescence spectroscopy provides an important tool
for the detection and probing of structure, dynamics and interactions of nucleic acid with relating
compounds. Many fluorescent nucleosides has been used as site-spectific probes for structure and
dynamic of nucleic acids studies. The fluorescent nucleosides are valuable as sensitive reporter
probes for detecting the change of the microenviroment in DNA.
In this paper, the fluorophore group such as carbazole, anthracene, and coumarin was introduced
to the 5’ terminus of the nucleoside(Fig1) by using the nucleoside hydrogen phosphonate diester
through reacting protected nucleoside with PCl3; followed by alcoholysis with corresponding
alcohol; protected nucleoside hydrogen phosphonate derivatives are obtained in reasonable yields.
If the mixture of primary alcohol and t-butanol(1:1) is used as alcoholysis agent, the
o-n-alkyl-5-H-phosphonate is generated when the primary alcohol has different fluorophore group.
A range of 5’-fluorescently lablled nucleosides were synthesized. The 5’-N-alkyl-carbazole
lablled nucleoside was synthesized and characterized by HNMR.ESI-MS, and fluorescence
spectroscopy. A lot of information associated with the structure and function of biomacromolecules
can be obtained by analyzing the fluctuation of fluorescence intensity and polarization.
LO
O
P
H
O
218
B
O
O O
L=fluorophore
B=uracil,Guanine

P-140
MICROWAVE-ASSISTED SYNTHESES OF 2',3'-O-ISOPROPYLIDENE
RIBONUCLEOSIDE 5'-MONOPHOSPHATES
Z. Wang, Y.F. Zhao*
The Key Laboratory of Bioorganic Phosphorus Chemistry, Ministry of Education, Department of Chemistry, School of
Life Sciences and Engineering, Tsinghua University, Beijing 100084. E-mail:zhaofy@tsinghua.edu.cn
Phosphate monoesters are some of the most important substances in medicina l chemistry,
materials chemistry, and so on. 1Many methods for preparing Nucleoside 5’-monophosphates have
been reported. 2 The application of microwaves, as an efficient heating source for organic
reactions , was recognized in the 1986. 3 Since then, numerous successful reactions with
dramatically enhanced reaction rates have been disclosed. 4-6 Very high yields and clean reactions
have been obtained using only small amounts of energy. We synthesize 5’-monophosphate of
ribonucleosides without the protection of amino groups of nucleobases. Since secondary hydroxy
groups of ribonucleosides also react with phosphoric acid, 2',3'-O-isopropylidene ribonucleosides
were used as substrates. The reactions of 2',3'-O-isopropylidene uridine (1), adenosine (2), cytidine
(3), and guanosine (4) with 2 equiv of phosphoric acid in the presence of tributylamine and
N-alkylimidazole, which is promoted by microwave irradiation in 500W, gave their
5'-monophosphates selectively in respective yields of 86, 86,71, and 83%. In contrast, that same
yields were obtained in Dehydrative Condensation reactions performed under microwave irradiation
can be completed within 4-5 min whereas 6-8 h is required with conventional heating. It is also
likely that the widespread acceptance of this technique, as an important tool for the development of
laboratory-scale environmentally conscious chemistry, will result in microwave synthesizer
becoming an integral part of every modern organic laboratory.
Reference
[1] Hayakawa, Y. Comprehensive Organic Synthesis; Trost, B. M., Fleming, I., Winterfeldt, E., Eds.; Pergamon:Oxford,
1991, 6, 601-630.
[2] Sakakura, A.; Katsukawa, M.; Ishihara, K. Selective Synthesis of Phosphate Monoesters by Dehydrative
219

Condensation of Phosphoric Acid and Alcohols Promoted by Nucleophilic Bases. Org. Lett. 2005, 7, 1999-2002.
[3] Gedye, R. et al. The use of microwave ovens for rapid organic synthesis. Tetrahedron Lett. 1986, 27, 279–282
[4] Larhed, M.; Hallberg, A. Microwave-Assisted High-Speed Chemistry: A New Technique in Drug Discovery. Drug
Discovery Today. 2001, 6, 406-416.
[5] Strauss, C. R.; Trainor, R. W. Invited Review-Developments in Microwave-Assisted Organic-Chemistry. Aust. J.
Chem. 1995, 48,1665-1692.
[6] Elander, N.; Jones, J. R.; Lu, S. Y.; Stone-Elander, S. Microwave-Enhanced Radiochemistry. Chem. Soc. Rev. 2000,
29,239-250.
220

P-141
THE CORRELATION BETWEEN THE ESTIMATED PARTITION COEFFICIENT P
AND CAPACITY FACTOR K OF AMINO ACIDS AND PHOSPHORYL AMINO ACIDS
Hongxia Liu, Canfang Zhao, Mian Liu, Yuyang Jiang*, Yufen Zhao
The Key Laboratory of Chemical Biology, Guangdong Province, Graduate School at Shenzhen, Tsinghua University,
Shenzhen 518055, P.R.China
The modifications of amino acids(aas) by phosphorylation, methylation, acetylation and
glycosylation play a key role in the regulation of the activities of proteins and peptides. In our group,
various N-(O, O-Diisopropyl) phosphoryl amino acids (Dipp-aas) were synthesized by
N-phosphoryl of amino acids with diisopropyl phosphite. For further investigation on the
bioavailability and pharmacokinetics of these compounds, we have also developed a practical
HPLC method with an NH2 column to analyse the stability of these Dipp-aas in different solution.
In this work, we observed the linear relationships between the estimated logarithm of partition
coefficient (n-octanol/water, Log P) and the logarithm of capacity factor (Log k) of Dipp-aas and
aas. The results showed that the correlation equations of Log P-Log k for dipp-aas was Log P
=6.3742 Log k +0.8615 (r2=0.9745) and for aas was Log P =-Log k-3.3147(r2=0.8052),
respectively. The diversity of slopes revealed that the separation mechanism of dipp-aas and aas
on NH2 column was very different. It implied that separation of Dipp-aas was likely based on the
reversed-phase partition mechanism, but for aas it was based on a weak ion-exchange mechanism.
The correlation equation of Log P-Log k could be applied to predict the retention times and to
optimize HPLC separation conditions of other N-(O,O-diisopropyl) phosphoryl amino acids and
peptides.
Acknowledgments
This work was supported by the National Natural Science Foundation of China (No. 20472043, 20572060, 20672068),
Mega-Project of Science Research of Ministry of Science and Technology of China (No.2005CCA03400) and the
Project of Science and Technology of Guangdong Province ( 2005A11601008, 06028200).
221

P-148
SYNTHESIS Of α, β-DIFLUOROMETHYLENEBISPHOSPHONATE ANALOGS OF
dNTPs: PROBES FOR DNA POLYMERASE β
Thomas G. Upton 1 , Boris A. Kashemirov 1 , Charles E. McKenna 1 ,*, Myron F. Goodman 1 , G. K. Surya Prakash 1 , Roman
Kultyshev 1 , Vinod K. Batra 2 , David D. Shock 2 , Lars C. Pedersen 2 , William A. Beard 2 , and Samuel H. Wilson 2
1 Department of Chemistry, University of Southern California, Los Angeles, CA 90089 USA
2 Laboratory of Structural Biology, NIEHS, Research Triangle Park, NC 27709 USA
In an ongoing study of the mechanisms underlying DNA polymerase β catalysis and fidelity we
have synthesized the dTPP, dATP and dCTP α, β-difluoromethylene analogs (1, 2, and 3,
respectively). These analogs cannot be cleaved by the enzyme due to their hydrolysis-resistant
Pα-C-Pβ group, replacing the phosphoric anhydride in the natural nucleotides. The dT and dA
nucleotide analogs 1 and 2 were previously synthesized by Blackburn et al. by reaction of the
corresponding dNMP 5’-tosylates 4, 5 with difluoromethylenebisphosphonate 6 followed by
coupling of the resultant dNDP analogs with p-NO2Bn phosphoric acid morpholidate and
deprotection by hydrogenolysis on Pd, which last step, however, is problematic with dC. We report
a convenient method for synthesis of 3, which can also be used to prepare purine nucleotide analogs
such as 2, in which the bisphosphonate nucleotide intermediate is phosphorylated enzymatically in
excellent yield using a catalytic amount of ATP together with excess PEP in HEPES buffer using a
mixture of PK and NDPK. Two-stage purification employing ion-exchange, then RP preparative
HPLC afforded the nucleotide analogs in exceptional purity, as determined by standard NMR,
HPLC and MS analysis, with suppression of the background primer extension activity that may be
observed with less pure preparations. The structure of the dT CF2 analog in a ternary complex with
pol β, primer and template and relevant enzyme inhibition data are discussed in an assessment of
α,β nucleotide analog binding to the active site.
222

O-167
SYNTHESIS OF BICYCLIC FUROPYRIMIDINE DEOXYNUCLEOSIDES
CONJUGATED WITH N-DIISOPROPYLPHOSPHORYL AMINO ACIDS
Qiang Xiao A *, Xuanye Jin B , Weihong Xiao A , Yong Ju B
aJiangxi Key Laboratory of Organic Chemistry, Jiangxi Science and Technology Normal University, Nanchang 330013,
P. R. China
bKey Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology, Ministry of Education, Department of
Chemistry, Tsinghua University, Beijing 100084, P. R. China
The bicyclic furo[2,3-d]pyrimidine nucleosides represent an entirely new class of fused furo
pyrimidine derivatives with highly selectivity for varicella-zoster virus (VZV). Although the precise
action mechanism of these analogues remains to be elucidated, it is clear that their antiviral activity
depending on the VZV-encoded thymidine kinase phosphorylation. In our project for developing
anti-VZV drugs, a series of 6-subsitituted furo[2,3-d]pyrimidine nucleosides conjugated with
N-diisopropylphosphoryl amino acids were synthesized (Scheme 1).
DMTO
d
HN
O
O N
O
OH
1
DMTO
I
a
N
O N
O
HO
4
DMTO
O
O
HN
O N
O
HO
NH 2
2
HO
O
NH
R
O P O
O
5a-e
O
223
N
O
e
c
HO
DMTO
N
O N
O
HO
O
HN
O
O N
O
HO
6a-e
3
NH
O
6a R= CH 3;6bR=PhCH 2
6c R= Isopropyl; 6d R= Pro-
Scheme 1. Synthesis of bicyclic furopyrimidine deoxynucleosides 6a-e
References
1. McGuigan, C.; Yarnold, C. J.; Jones, G. et al J. Med. Chem.1999, 42, 4479-4484.
2. Cheng CM, Liu XH, Zhao YF, et al. Origin Life Evol. Bio. 2004, 34, 455-464.
O
NH
P
O
R
O
NH 2

P-168
EFFECTS OF CHRYSIN AND ITS TETRAETHYL BIS-PHOSPHORIC
ESTER IN THE CELL CYCLE AND P 21/WAF1 PROTEINS OF THE HUMAN
CERVICAL CARCINOMA CELL LINE HELA
Ting Zhang 1,2 , Xiaolan Chen 1 , Lingbo Qu 1 , Manji Sun 2 , Yufen Zhao 3
1. Key Laboratory of Chemical Biology, Department of Chemistry, Zhengzhou University, Zhengzhou, 450052
2. Institute of Toxicology and Medicine, Academy of Military Medical Sciences, Beijing 100850, China
3.The Key Laboratory for Bioorganic Phosphorus Chemistry, Department of Chemistry School of Life Sciences and
Engineering, Tsinghua University, Beijing 100084
Abstract Aim: To investigate the influences of CR/CP on the cell cycle and p 21WAF1 expression
in the human cervical carcinoma cell line (Hela). Methods: human cervical carcinoma cell line
(Hela) was treated with 10μM CR and CP respectively , the cell cycle and p 21WAF1 expression was
determined with flow cytometry (FCM) and western immunobloting methods. Results: The cell
cycle distribution and p 21WAF1 expression in the Hela cells treated with CR/CP were changed
markedly as compared to vehicle-treated Control. The CR treatment resulted in an appreciable
increase in the G0/G1 phase cell population and a decrease in the S phase cell populations,
accompanied by up-regulation of p 21WAF1 expression. The CP could increase both in the G0/G1
phase and G2/M phase cell populations, and induce p 21/WAF1 expression. Conclusion: CP could
arrest cell cycle in both G0/G1 and G2/M phases accompanied with up-regulation p 21/WAF1
expression, whereas CR only arrest G0/G1 phase cell cycle and induct p 21/WAF1 in Hela cells. This
indicated that the CR and CP could arrest cell cycle of Hela cells in different ways.
224

P-170
THE PEPTIDE BOND FORMATION REACTION WITH PEPTIDES AND PROTEINS IN
AQUEOUS SOLUTION BY INDUCEMENT OF N-PHOSPHORYL α-AMINO ACIDS
Jia Ning Wang a, b , Yan Liu a , Dacheng He b , a
, Yu-Fen Zhao*
a. The Key Laboratory for Chemical Biology of Fujian Province, Department of Chemistry, Xiamen University,
Xiamen, 361005, P. R. China
b. The Key Laboratory for Cell Proliferation and Regulation Biology of Ministry of Education, College of Life Science,
Beijing Normal University, Beijing 100875, P. R. China
Jia Ning Wang: Tel: 13391726204; E-mail address: spaceman_jia@126.com
In the work described in this paper, it was found that N-phosphoryl α-amino acids played an
important role in the formation of long-peptides and proteins in aqueous solution under mild
conditions (37℃) by mean of mass spectrometry.
Due to the inducement of N-phosphoryl α-amino acids such as
N-(O,O’-diisopropyl)phospho-L-α-alanine (abbr:N-DIPP-L-α-Ala), some different length peptides
or proteins, such as GHRF(29 amino acid residues) and cytochrome c(104 amino acid residues),
were added one amino acid residue to its N-terminal amino group in aqueous solution, respectively.
The deconvoluted mass spectrogram showed that an additional increased MW of original
peptide/protein could be detected. The mass difference of m/z of original peptide/protein and newly
produced peak is almost the mass number of alanine residue (Mw: 71.1), if the added N-phosphoryl
α-amino acid is N-DIPP-L-α-Ala. The relative intensity of m/z at M+71 which corresponding one
alanine residue added to peptide/protein would increase when extended the incubation time of
N-DIPP-L-α-Ala with peptide/protein.
The strict proof and features of this peptide bond formation reaction was investigated through
ESI-MS/MS by using different phosphoryl amino acids incubate with various modified and
unmodified synthetic peptides such as Ala-Gln. The results showed that whenever a kind of
N-DIPP-α-Amino acids was added to incubate with Ala-Gln. The resulting tripeptides would be
detected and described as X-Ala-Gln. X represented amino acid residue from N-DIPP-α-Amino
acid as reactant. This experiment results indicate that the addition of mass near 71.1Da represented
alanine residue, and the added amino acid residue rooted in N-phosphoryl α-amino acid. The results
of further incubation experiments by using modified peptides which N-terminal amino group was
blocked but side chain native amino group was unchanged, showed that only α-amino
group(N-terminal amino group) of peptides can be involved in the peptide bond formation reaction.
In this study, two non-α-amino acids, N-DIPP-β-Ala and O-DIPP-α-Ser, were chosen to incubate
with Ala-Gln in aqueous solution at the same condition respectively. The mass spectrum results
showed that no peek indicating any peptides formed even incubated for 17 days. Considering the
structure of natural α-amino acids and the intermediate described before, any non-natural amino
acids, which structurally cannot form five membered ring cyclic penta-coordinate
phosphoric-carboxylic mixed anhydride may not be able to form peptides[1]. The corresponding
mechanism of the peptide bond formation reaction has been speculated that the five-membered ring
penta-coordinate phosphoric intermediate may be involved in the process[2,3]. This mechanism
suggested that why nature chose α-amino acids as primary blocks of protein.
225

References
[1] Jiang Y, Tan B, Chen ZZ, et al. Phosphoryl group differentiating alpha-amino acids from beta- and gamma-amino
acids in prebiotic peptide formation. Int. J. Quant. Chem 2003 94 : 232-241
[2] Fu H, Li Z L, Zhao Y F, et al. Oligomerization of N,O-bis(trimethylsilyl)-alpha-amino-acids into peptides mediated
by o-phenylene phosphorochloridate. J. Am. Chem. Soc., 1999, 121: 291-295
[3] Fu H, Tu G Z, Li Z L et al. New and efficient approach to eht synthesis of penta-coordinate spirobicyclic
phosphoranes. J. Chem. Soc., Perkin Trans., 1997, 1:2021-2022
226

P-172
THE SYNTHESIS AND RESOLUTION OF THE OPTICLE ACTIVE DERIVATIVES OF
N-THIOPHOSPHORAMIDATE DERIVATIVES
Anfu Hu, Peng Liu , Pengxiang Xu ,Yufen Zhao*
Department of Chemistry and The Key Laboratory for Chemical Biology of Fujian Province, College of Chemistry and
Chemical Engineering, Xiamen University, Xiamen 361005, P. R. China.
Introduced by Eckstein, phosphorothioate analogues of nucleotides have become an
indispensable tool for studying the metabolism of nucleic acids. [1] However, the enzymatic synthesis
of stereodefined oligo(deoxyribonucleoside phosphorothioate)s (PS-Oligos) is limited to the
preparation of (all-Rp)-oligomers because of the stereoselectivity of available DNA and RNA
polymerases. Stereodefined PS-Oligos were used for studying the mode of action of several
bacterial and human enzymes [2] , and the stereodependent avidity of PS-Oligos toward
complementary DNA or RNA. [3] So obtaining a pure diastereoisomer is very important.
In this article, we report a convenient and efficient approach for the synthesis of
N-thiophosphoramidate derivatives of nucleosides (1 and 2), depicted in Scheme 1, with total yield
70-80%. The diastereoisomeric mixtures(1:1 ratio) were isolated by silica gel chromatography.
R
O
P
Cl
Cl Cl
P
O
P
Cl
R
O
or
Cl
O
O N
O O
+
O
NH
O
O
NH
O N
O
HO
HO
O
or
O N
O
O N
O
NH
O
O
NH
O
-5℃ CH 2Cl 2
3h
NH 2CHR'CHOOCH 3 S powder
R.T. overnight
227
Cl
P
Cl
Cl
P
Cl
O
O
O
NH
O N
O
O O
or
O N
O N
R S
O P O
HN
R'
O
O O O
or
R S
O P O
HN
R'
O
O
O N
O
NH
O
O
NH
O
O
NH
O
ROH Et 3N -40℃
CH 2Cl 2 0.5h
SCHEME 1. Synthesis of N-thiophosphoramidate derivatives
1
2
R= CH 3 1a
CH 3CH 2 1b
CH 2Ph
1c
1d
R'=H 2a
CH 3 2b
CH 2Ph 2c
CH(CH 3) 2 2d
Reference
[1] F. Eckstein, Antisense Nucleic Acid Drug Dev. 2000, 10, 117 -121.
[2] C. A. Brautigam, T. A. Steitz, J. Mol. Biol. 1998, 277, 363-377.
[3] W. J. Stec, B. Karwowski, M. Boczkowska, P. Guga, M. Kozioøkiewicz, M. Sochacki, M.Wieczorek, J. Bøaszczyk,
J. Am. Chem. Soc. 1998, 120, 7156- 7167.

P-176
NEW β-FERROCENYL PHOSPHINO α-AMINOACIDS AS MODULAR
ELECTROCHEMICAL BIOMARKER FOR CSF114(GLYCO)PEPTIDES
A. Colson a , J. Bayardon, a E. Rémond, a F. Nuti, b R. Meunier-Prest, a M. Kubicky, a
C. Darcel, a A.M. Papini b and S. Jugé* a
a) Inst. Chim.Mol. de l'Université de Bourgogne,UMR CNRS 5620, 9 av. A. Savary, 21078 Dijon, France; Fax 33 3 80
39 60 98; Email: Sylvain.Juge@u-bourgogne.fr
b) Lab. de Chimie et Biologie de Peptides et Protéines, Université de Florence, I 50019, Italie
In the recent period, organometallic probes have found considerable interest to mark all kinds of
bioactive compounds, in order to improve their control by absorptiometry, immuno- or
electro-chemical methods. 1 Meanwhile, several α-aminoacids bearing a metallocenyl substituent
have been synthesized, mainly by a carbon-carbon bond formation strategy on the side chain. 1b
We report herein a new efficient route for the diastereoselective synthesis of ferrocenyl aminoacid
derivative 3, by grafting the organometallic part on the aspartic backbone 1, using a phosphine borane
linker. 2
HO 2C
1
CO 2H
NH 2
Fc
Ph
BH 3
P
2
CO 2Bn
NBoc 2
53% isolated yield
The interest of the phosphine borane group arises from its direct use for oxidation, sulfuration,
quaternization or complexation, 3 allowing the synthesis of various kinds of ferrocenyl aminoacid
derivatives, starting from 2 used as a platform. Thus, after sulfuration, the sulfide derivative is
hydrolyzed into its corresponding free acid 3, useful for the peptide synthesis.
In addition, the electrochemical investigation of the ferrocenyl aminoacid derivatives 2,3, and their
use to mark the CSF114glc, a synthetic antigen specific of the mutiple sclerosis auto-antibodies, 4 are
reported.
Reference
1) a) R. H. Fish, G. Jaouen Organometallics 2003, 22, 2166. b) H. Dialer, K. Polborn, W. Ponikwar, K. Sünkel, W.
Beck Chem. Eur. J. 2002, 8, 691.
2) For a recent work on organophosphorus amino acids synthesis, see: F. Meyer, A. Laaziri, A.M. Papini, J. Uziel, S.
Jugé Tetrahedron 2004, 60, 3593.
3) J. Uziel, C. Darcel, D. Moulin, C. Bauduin, S. Jugé Tetrahedron: Asymmetry 2001, 12, 1441.
4) F. Lolli, B. Mulinacci, A. Carotenuto, B. Bonetti, G. Sabatino, B. Mazzanti, A.M. D'Ursi, E. Novellino, M. Pazzagli,
L. Lovato, M.C. Alcaro, E. Peroni, M.C. Pozo-Carrero, F. Nuti, L. Battistini, G. Borsellino, M. Chelli, P. Rovero, A.M.
Papini, Proc. Natl. Acad. Sci. USA 2005, 102, 10273.
228
S
Fc
P
Ph
3
CO 2H
NHBoc

P-183
A STUDY ON THE NUCLEOSIDE ANALOGS USING ELECTROSPRAY
IONIZATION MASS SPECTROMETRY
Liu Ruoyu 1 , Ye Yong 1 , Cao Shuxia ,Liao Xincheng 1 , Zhao Yufen 1,2
1.The Key Laboratory of Chemical Biology and Organic Chemistry of Henan Province, Department of Chemistry,
Zhengzhou University, Zhengzhou 450052, China;
2.The Key Laboratory for Bioorganic Phosphorus Chemistry and Chemical Biology, Ministry of Education, Department
of Chemistry School of Life Sciences and Engineering, TsinghuaUniversity, Beijing 100084, China
As anti-HIV prodrugs, nucleotide analogs have received considerable attention in medicinal
chemistry. One of the uridin analogs was synthesized and the structure was determinded by using
electrospray ionization mass spectrometry (ESI-MS) in conjunction with tandem mass
spectrometry(MS/MS) in positive and negative mode. The fragmentation pathways were
investigated in details. It was found that the fragmentation ions in the positive is very different from
those in the negtive.
m/z=283
NH 2
N
HO
O
H H
H H
O O
N
O
O
-40
NH 2
N
C
N
CH 2
O
m/z=152
NH 2
N
HO
O
H H
H H
OH OH
m/z=242
-90
NH 2
N
N
N
-132
O
m/z=110
O
229
-43
N
N
HO
O
H H
H H
OH OH
N
N
HO
O
H H
O
m/z=181
m/z=199
-18
-18
N
N
HO
O
H H
O
m/z=181
N
N
HO
m/z=123
References
[1] Sun Xiaobin. Studies on Novel Synthesis of Antiviral Nucleoside H-Phosphonate Diester and Phosphoramidate
Derivatives: [Doctor Paper]. Beijing.Chemistry Department of Tsinghua University.
[2] Chen Yi. Study of the Anti-HIV Prodrugs and the Non-covalent Complexes with proteins by Electrospray Ionization
Mass Spectrometry. [Doctor Paper]. Beijing.Chemistry Department of Tsinghua University.
[3] Qiang Xiao,Yong Ju,Xinping Yang etc.Electrospray ionization mass spectrometry of AZT H-phosphonates
conjugated with steroids. Rapid commun.Mass Spectrom.2003;17;1405-1410

P-184
STUDIES ON THE NONCOVALENT BONDING BETWEEN ATP AND
α-AMINOPHOSPHONIC ACIDS DERIVATIVES BY ESI-MS AND
MOLECULAR MODELING
Liu Xiaoxia, Fang Hua, Liu Yan, Zhao Yufen *
The Key Laboratory for Chemical Biology of Fujian Province, Department of Chemistry and College of Chemistry and
Chemical Engineering, Xiamen University, Xiamen 361005, P. R. China
To investigate molecular recognition of ATP with proteins or structured peptide-based receptor
[1,2]
is very important for understanding enzymatic mechanisms and drug design .
α-Aminophosphonic acids and their derivatives, as phosphorous analogs of amino acid, behaved
more biological activities and attracted much attention [3] . In this work, Diisopropyl
[phenyl(pyridine-4-carboxamido) -methyl]phosphonate (Figure 1a) was synthesized for
investigating the interaction with ATP. The noncovalent complex was observed by the Electrospray
ionization Mass Spectrometry (ESI-MS). Using the Molecular modeling [4] , it was observed that
there were two intermolecular hydrogen bonds in the noncovalent complex. (Table 1) The binding
energy was - 8.999kcals/mol, which was reasonable. In order to investigate the function of
phosphoryl group in the interaction, benzoyl phenylglycine isopropyl ester (Figure 1b), was
synthesized. Interestingly, there wasn’t interaction between ATP and compound 1b to be observed
by ESI-MS. The above experiment results implied that phosphoryl group was very important for the
interaction between α-Aminophosphonic acids and ATP.
15 16
14
4
3 O 1
O 17
1 H P 19
8 7
2
N 13
O 2
1 N
11
12
6 5
9 10
1 O 1
4
2 3
a
18
Figure 1 The structure of (a) Diisopropyl [phenyl(pyridine-4-carboxamido)methyl]phosphonate (b)
benzoyl phenylglycine isopropyl ester
X---H---Y(symm code)
X---Y(nm) X---H---Y(degree)
(compound 1a ---ATP)
N(2)-H(1)---O(12) 2.906 134.56
P(1)=O(2)---H(1)-N(1) 2.877 160.68
Table 1 Hydrogen Bonds geometry
Reference
[1] Lisong Mao,; Yanli Wang,; Yuemin Liu,; Xiche Hu, J. Am. Chem. Soc. 2003, 125:14216
[2]Sara M. B.; Marcey L. W., J. Am. Chem. Soc. 2003, 125:9580
[3]Fang, H.; Fang, M. J.; Liu, X. X.; Xu, P. X.; Zhao, Y. F., Chin. J. Org. Chem., 2005, 25:466
[4]Sybyl 7.1; Tripos Inc.: St. Louis, MO.
230
O
O
C
O
CH
b
C
NH

P-185
PEPTIDE BOND FORMATION ON C-TERMINAL OF PEPTIDES IN ORGANIC
SOLUTION BY INDUCEMENT OF N-PHOSPHORYL AMINO ACID
Liu Xiaoxia, Liu Yan, Zhao Yufen *
The Key Laboratory for Chemical Biology of Fujian Province, Department of Chemistry and College of Chemistry and
Chemical Engineering, Xiamen University, Xiamen 361005, P. R. China
Peptide formation is one of the most important reactions in prebiotic evolution. And
N-phosphoryl-α-amino acids were proposed as model for the co-evolution of proteins and nucleic
acid [1-4] . It was reported previously that the N-phosphoryl-homo, di- or tri-peptide could be
formed through the self-activation reaction [5-7] . In this paper, tetrapeptide (FGGF), and
heptapeptide (Ac-NH-LKKTETQ-OH) were incubated with N-phosphoalanine in pyridine solution.
The resulting products were analyzed by ESI-MS/MS. It was found that peptides were prolonged by
adding alanine residue both from on N-terminal and C-terminal (Table 1). Compared with the
N-terminal reaction [8] , the mechanism of alanine adding on C-terminal had never reported. The
possible mechanism was speculated that the five-membered ring penta-coordinate phosphoric
intermediate played an important role in the reaction (Scheme 1). In order to prove the mechanism,
N-protected tetrapeptide (Fmoc-NH-FGGF-COOH) was incubated with N-phosphoalanine in the
same condition. Through ESI-MS/MS analysis, there was nothing more than the addition of alanine
on C-terminal to be observed (Table 1).
Dipp-Ala
HO O
O
C
O P
CH
O N
CH3 H
O O O O
H2N CH C NH CH C NH CH C NH CH C O
CH2 H H CH2 O O O O O
H2N CH C NH CH C NH CH C NH CH C NH CH C OH
CH2 H H CH2 CH3 FGGFA 1b
231
Dipp-Ala
O
O CH3 HO O C C NH
O P
O
O
O
H
FGGF NH2 O
O
O P NH CH C NH CH C NH CH C NH CH C NH CH C OH
O CH2 H H CH2 CH3 Dipp-FGGFA 1d
Scheme 1 the possible mechanism of alanine added on C-terminal of peptide
Precursor ions(m/z) Main Fragments ions (m/z) (abundance, %)
AFGGF
FGGFA
498
333(63)
409(93)
276(15)
262(14)
219(7)
205(4)
Dipp-AFGGF
Dipp-FGGFA
662
497(54)
573(80)
440(40)
427(9)
383(29) 236(4)
Ac-LKKTETQA
Ac-L(ε-A)KKTETQ
960
814(100)
871(18)
713(69)
743(7)
584(19)
642(9)
483(20)
513(12)
355(11)
412(8) 284(5)
Fmoc-FGGFA 720 631(50) 484(9)
Table1 Multi-stage mass spectra of protonated Precursor ions
Reference
1. Zhao YF, Cao PS. Phosphorus, Sulfur Silicon. 1999; 144-146: 757.
2. Zhao YF, Cao PS. Pure Appl.Chem. 1999; 71(6):1163.
3. Ju Y, Zhao YF, Sha YW, Tan B. Phosphorus Sulfur and Silicon and the Related Elements. 1995; 101: 117.
4. Ji GJ, Xue CB, Zeng JN, Li LP, Chai WG, Zhao YF. Synthesis-Stuttgart.1988; 6: 444.
5. Hu JJ, Ju Y, Zhao YF. Chinese J. of Chem. 2000; 18 (6): 932.
6. Lu K, Liu Y, Zhou N, Chen Y, Feng YP, Guo XF, Chen W, Qu LB, Zhao YF. Acta Chimica Sinica. 2002; 60 (2):
372.
7. Zhao YF, Ju Y, Li YM, Wang Q, Yin YW, Tan B. International J. of Peptide and Protein Research. 1995; 45 (6):
514.
8. Fu H, Li ZL, Zhao YF, Tu GZ. J. Am. Chem. Soc. 1999; 121 (2): 291.
O
O
OH

P-193
SYNTHESIS OF O-NUCLEOSIDE N-PHOSPHORYL AMINO
ACID METHYL ESTER
Chen Wei-Zhu 1,2 , Gao Yu-Xing 2 , Li Gang 2 2 *
, Zhao Yu-Fen
1 The Third Institute of Oceanography of The State Oceanic Administration, Xiamen 361005, P. R. China
2 The Key Laboratory for Chemical Biology of Fujian Province,Department of Chemistry, College of Chemistry and
Chemical Engineering, Xiamen 361005, P. R. China
Recently, O-nucleoside N-phosphoryl amino acids are continuing to be an important class of
rationally designed antiviral nucleoside prodrugs 1 and the model molecules in the study of the
prebiotic biosynthesis of proteins 2 . Increasing interest in such compounds has provided the impetus
for the development of a general synthetic method.
In the present dissertation, we reported the application of Atherton-Todd reaction 3 in the
synthesis of O-alkyl O-2’,3’-isopropylideneuridine N-phosphoryl amino acid methyl ester (Scheme
1). Firstly, by Abuzov reaction, one-pot synthesis of hydrogen phosphonate derivatives of protected
nucleoside by reacting protected nucleoside with PCl3, followed by alcoholysis with corresponding
alcohols, protected nucleoside 5'-H-phosphonates derivatives were obtained in reasonable yields.
By using mixture of t-butanol and menthol (1:1) as alcoholysis agents, the protected nucleoside
5'-H-phosphonates derivatives were generated in satisfactory yields. Then the amino acid methyl
ester 5'-phosphoramidates of nucleoside were synthesized in the presence of Et3N and CCl4 in high
yields by Atherton-Todd reaction 3 . Excellent coupling yields were noted in the reaction of 3 with
amino acid methyl ester of glycine, alanine, leucine, proline, methionine, histidine and
phenylalanine.Their structures were confirmed by 1 H NMR, 31 P NMR, 13 C NMR and MS spectra.
The present methodology was applicable to amino acid methyl esters with different side
chains and with either of the nucleosid-3’ (or 5’)-yl H-phosphonates. Compared with other
methodologies, this method is a fast, convenient and efficient method in mild reaction conditions.
HO
O
O
O N
O
HP
O
O
NH
O
+ Cl P
Cl
Cl
O N
i
232
Cl
P
Cl
O
O
O
O N
O O
1
NH
2
NH
O
3
O
O
O
O
NH
O
ii
iii
iv O N
O R O
H
H3C O C C N P O
H
O
O O
4
Reagents and condition: (i) NEt3, dry CH2Cl2, 0 °C for 0.5 h, then room temperature for 3 h; (ii)
dry CH2Cl2, menthol, tert-butyl alcohol, 0 °C, then room temperature for 0.5 h; (iii) NEt3 ,dry
CH2Cl2, 0 °C, then room temperature for 10 min; (iv) CCl4, NEt3, H2O, CH3CN, AAOCH3, room
temperature.
Scheme 1 Synthetic route of O-nucleoside N-phosphoryl amino acid methyl ester
References
1. McGuigan, C; Cahard, D.; Sheeka, H. M.; Clercq, E. D.; Balzarrini, J. J. Med. Chem., 1996, 39, 1748-1753.
2. Zhao, Y. F.; Cao P. S. J. Biol. Phys. 1994, 20, 283-287.
3. Atherton, F. R.; Todd, A. R. J. Chem. Soc. 1947, 674-678.
O

P-195
PROTEIN PHOSPHORYLATION REGULATES PROTEIN LOCAL STRUCTURE AND
FUNCTION
Jia Hu, Yu-Fen Zhao, Yan-Mei Li *
Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (ministry of Education), Department of
Chemistry, Tsinghua University, Beijing 100084, P. R. China
Protein phosphorylation is one of the most important forms of protein post-translational
modifications. Reversible phosphorylation is related to most physiological and pathological
processes. Some of our recent results concerning how phosphorylation participates in modulating
protein local structure and adjusting protein properties were summarized in this article.
233

P-197
A FAST WAY TO SYNTHESIS NUCLEOSIDE H-PHOSPHONATE DERIVATIVES
Jian-Bin Wu 1 , Jian-Nan Guo 1 , Jun Zhang 3 , Shu-Na Luo 1 , Xiang Gao 1 , Yu-Fen Zhao* 1,2
1
Department of Chemistry, School of Chemistry & Chemical Engineering, Xiamen University, Xiamen, P.R.China,
361005
2
The Key Laboratory of Bio-organic Phosphorus Chemistry, Ministry of Education, Department of Chemistry, School
of Life Science & Engineering, Tsinghua University, Beijing, P.R.China, 100084
3
Department of Biology, School of Life Science, Xiamen University, Xiamen, P.R.China, 361005
The O-alkyl-5A-H-phosphonates of d4T or AZT have been proved to cause less
nucleoside-resistant mutants of HIV, lower cytotoxicity, and higher anti-HIV activity due to easier
membrane permeability of these derivatives resulting from the presence of the lipophilic group. [1]
Here we report a novel fast way to synthesis O-alkyl-H-phosphonate of d4T using condensation
reagent 2-chloro-1,3-dimethylimidazolinium chloride (DMC). A typical process is showed in
scheme 1.
HO
O
d4T
O
N
NH
O
+
Table 1 ROH 1~7
H 3PO 3
DMC
pyridine, rt
scheme 1
234
DMC, ROH 1~7
pyridine, rt
1 2 3 4 5 6 7
OH OH OH
OH HOCH2(CH 2) 16CH 3
RO
O
P
H
O
O
a 1~7
OH OH
Typical procedure: DMC(1.2eq) is dissolve in dried CH2Cl2, then is dropped to a flask containing
d4T(1eq) and H3PO3(1.1eq) in newly freshed pyridine. The reaction mixture is stirred at room
temperature. After 5 minutes alcohol ROH(1eq) is added to the above flask and then another 1.2eq
DMC in dried CH2Cl2 is dropped to the flask at room temperature.The second step finish within
10minutes. The solvent is removed in vacuum and the raw product is purified over silica gel column
chromatography using CH2Cl2/MeOH(20:1) as eluent to give yields from 45%-66% according to
different alcohol.
References:
[1] XiaoBin Sun, JianXun Kang, YuFen Zhao. One-pot synthesis of hydrogen phosphonate derivatives of d4T and AZT.
Chem. Commun. 2002, 20: 2414~2415
O
N
NH
O

Symposium 5
Theoretical Aspects of Phosphorus Chemistry ;
31 P NMR in Biological Systems

KL-7
MOLECULAR SIMULATION STUDIES OF PROTEIN KINASES
Martin J. Field
Laboratoire de Dynamique Moleculaire, Institut de Biologie Structurale - Jean-Pierre Ebel, 41, rue Jules Horowitz,
38027 Grenoble Cedex 1, France
An important goal of computational and theoretical biochemistry is helping elucidate how
enzymes achieve their catalytic efficiency. The extended nature of such systems, however, makes
this a challenging task for simulation techniques. Powerful approaches for the investigation of
enzymatic and other condensed phase reaction processes are quantum chemical, molecular
dynamical and hybrid potential techniques 1 . This talk will describe the combination of techniques
employed in the author's group and illustrate their use by a discussion of their application to
simulations of protein kinases. 2
Reference
1. Field, M. J.; Albe, M.; Bret, C.; et al. Jounal of Computational Chemistry 2000, 21(12), 1088.
2. Diaz N, Field M. J., Journal of The American Chemical Society 126 (2): 529-542 JAN 21 2004
235

KL-8
FROM POWDER NMR TENSOR TO 3D MOLECULAR STRUCTURE,
PROMISES OR ILLUSION - A 31P AND 13C CASE STUDY ON CIMITIDINE
Steve C.F. Au-yeung
The Chinese University of Hong Kong, P.R.China
236

IL-15
NMR INVESTIGATIONS OF PHOSPHATE TRANSFER ENZYMES
Jonathan P. Waltho
Department of Molecular Biology and Biotechnology, University of Sheffield, Sheffield S10 2TN, UK.
The interpretation of a structure of beta-phosphoglucomutase (PGM) complexed with G6P as a
pentacovalent trigonal bipyrimidal phosphorus intermediate[1] raised many questions as to how
phosphoryl transfer is achieved in a wide variety of enzymes. Using 31P and 19F NMR
spectroscopy, we have established that the trigonal-bipyramidal (TBP) species was misinterpreted
and is in fact magnesium trifluoride, MgF3, rather than a phosphorane species[2]. However, the
bonding in the TBP accurately portrays the transition state for phosphoryl transfer in PGM and
reveals the details of protein catalysis. Using similar methods we have extended this investigation to
a range of similar and dissimilar enzymes, namely phosphoserine phosphatase, phosphoglycerate
kinase, and F1-ATPase.
References
1. Lahiri, S.D.; Zhang, G.; Dunaway-Mariano, D.; et al. Science (2003), 299, 2067-2071.
2. Baxter, N.J.; Olguin, L.F., Golicnik, M.; et al. Proc. Natl. Acad. Sci. USA (2006), 103, 14732-14737.
237

IL-16
PHOTOPHYSICS OF DNA AND LIGHT HARVESTING SYSTEMS
GuanHua Chen
Department of Chemistry, The University of Hong Kong, HK, P.R.China
Using the linear-scaling localized-density-matrix method, we have calculated the excited states of
a single-stranded adenine bases and a light harvesting system II (LH2), and propose a unified
Frenkel exciton description of these excited states.
238

IL-18
QM-MM COMPUTATION OF PHOSPHATE TRANSFER BY ENZYMES
Charles E. Webster
Department of Chemistry, The University of Memphis, Memphis, TN 38152, USA
Two-layered ONIOM(B3LYP:PM3) calculations
have been utilized to address the nature of the
β-phosphoglucomutase (β-PGM) enzyme active site
structure and shed light on the identity of the five
coordinate atom, Y, and its ligation (see Scheme). The
reported crystal structure of β-PGM was refined as a
five-coordinate phosphorus (with five oxygen ligands),
which the authors suggested was a "high-energy
reaction intermediate" for phosphoryl transfer in the isomerization of β-glucose 1-phosphate to
β-glucose 6-phosphate. The active site of β-PGM has a five coordinate atom (Y=P or Mg) and a
pseudooctahedral Mg, coordinated by four terminal ligands (two H2O, an oxygen from ASP170,
and a backbone oxygen from ASP10) and two bridging ligands (an oxygen from ASP8 and a
bridging atom, Xb, to the five-coordinate species, Y). Conclusions from the current computational
study include 1) the observed crystal structure is more consistent with a five-coordinate magnesium
(a stable transition-state analogue), not a five-coordinate phosphorus (a phosphorane) and 2) the
transfer of the phosphoryl group proceeds through a concerted fivecoordinate phosphorus transition
state that is directly coupled to a proton transfer from the oxygen of bound glucose to the carboxylic
group of aspartate 10. Our further work on this system will also be discussed.
239

O-44
1.3-DIPHOSPHACYCLOBUTANE-DIYLS AS BUILDING BLOCKS
FOR EXTENDED STRUCTURES
Wolfgang W. Schoeller,
Department of Chemistry, University of Bielefeld,
33615 Bielefeld (Germany) and Department of Chemistry,
University of California at Riverside (USA)
The structures 1[1] and 2[2] are isolable biradicaloids, but with different electronic properties[3].
In the present contribution the effects of substituents (R´, R´´= alkyl, aryl, TMS) which determine
the biradical character in 1 and 2 are discussed. Furthermore, the design of extended structures such
as 3, with biradicaloid units linked over a -spacer (e.g. phenyl), is analyzed. The coupling of the
unpaired electrons is studied by a combination of MCSCF and DFT procedures.
R´
P
R´´ C
C R´´
C
1
P
P
C
P
R´
240
R´ R´
P
R´´ B
B R´´
π-spacer C
C 3
Reference
[1] E. Niecke, A. Fuchs, F. Baumeister, M. Nieger, W.W. Schoeller, Angew. Chem. Intern. Ed. 1995, 34, 555. H.
Sugiyama, S. Ito, M. Yoshifuji, Angew. Chem. Intern. Ed. 2003, 42, 3802.
[2] D. Scheschkewitz, H. Amii, H. Gornitzka, W.W. Schoeller, D. Bourissou, G. Bertrand, Science 2002, 295, 1880.
[3] W.W. Schoeller, C. Begemann, E. Niecke, D. Gudat, J. Phys. Chem. A 2001, 105, 10731. W.W. Schoeller, A.
Rozhenko, D. Bourissou, G. Bertrand, Chem. Eur. J. 2003, 9, 3611.
R´
P
P
P
R´
2

O-45
DEVELOPMENT OF A BIDENTATE LIGAND BASED ON
DECAFLUORO-3-PHENYL-3-PENTANOL: STERIC EFFECT OF
PENTAFLUOROETHYL GROUPS ON THE STEREOMUTATION
OF OEQUATORIAL C-APICAL SPIROPHOSPHORANES
Y.Yamamoto*†, X.d.Jiang†, K.I.Kakuda†, S. Matsukawa§, H.Yamamichi†
† Department of Chemistry, Graduate School of Science, Hiroshima University
1-3-1 Kagamiyama, Higashi-hiroshima 739-8526, Japan
§ Institute for Advanced Materials Research, Hiroshima University
1-3-1 Kagamiyama, Higashi-hiroshima 739-8530, Japan
1,1,1,2,2,4,4,5,5,5-Decafluoro-3-phenyl-3-pentanol (1) was prepared from pentafluoro
-propiophenone via the Cannizzaro-type disproportionation reaction.1 Dimetallated 1 (i.e., 2) was
used as a bidentate ligand, which was bulkier than the Martin ligand (1,1,1,3,3,3-hexafluoro-
2-phenyl-2-propanol). P-H spirophosphorane (3) was synthesized utilizing the new bidentate ligand.
Phosphoranes which exhibit reversed apicophilicity (4: Oequatorial) were also synthesized and
could be converted to the corresponding stable stereoisomers (5: O-apical). The crystal structures of
O-equatorial phosphoranes (4) and those of O-apical isomers (5) were slightly affected by the steric
repulsion of C2F5 groups.
Kinetic measurements revealed that the stereomutation of O-equatorial methylphosphorane (4a)
to the O-apical isomer (5a) was slowed. The activation enthalpy for the stereomutation of 4a→5a
(24.4 kcal mol–1) was higher than that of the phosphorane bearing the Martin ligands (6a→7a: 19.3
kcal mol–1) by 5.1 kcal mol–1.
References
[1] Jiang, X.-D.; Kakuda, K.-i.; Matsukawa, S.; Yamamichi, H.; Kojima, S.; Yamamoto, Y. Chem. Asian J. 2007, 2, in
press.
241

O-46
CONFORMATIONAL ANALYSIS OF 1,4-HETEROPHOSPHINANES
Ya.A. Vereshchagina, a, b E.A. Ishmaeva, b A.A. Gazizova, a D.V. Chachkov, a M.G. Voronkov c
a Kazan State Technological University, K. Marks St., 68, Kazan, 420015, b Kazan State University, Kremlevskaya St.,
18, Kazan, 420008, andc A.E. Favorsky Irkutsk Institute of Chemistry SB of RAS, Favorsky St., 1, Irkutsk, 664033,
Russian Federation; e-mail: yavereshchagina@yahoo.com
We carried out a conformational analysis of 1,4-heterophosphinanes 1-3 by the methods of dipole
moments, Kerr effect, molecular mechanics, and quantum chemical calculations (DFT
B3LYP/6-31G*).
Y 1 X = S, Y = Se
X P 2 X = SiMe2, Y = Se
Ph
3 X = SiMe2, Y = lone pair of electrons
Chair conformations were the energetical preferred for compounds 1-3 according to the data of
MM calculations.Experimental and calculated (vector-additive scheme) dipole moments for chair
conformations of compounds 1-3 are presented below. The conformer with equatorial orientation of
the phenyl substituent (chaire) was preferred for all compounds by the data of dipole moments
method.
Y
Ph
№
µcalc, D
µexpt, D,
P
P
Ph
Y
chaira chaire dioxane
X
X
1 4.07 4.31 4.39
chaire chaira 2 4.71 5.13 5.30
3 0.96 1.87 1.82
Analysis of experimental and calculated Kerr constants of phosphinane 2 led to a conclusion that
chair conformation of heterocycle with parallel arrangement of the Ph ring and the P=Se group was
preferred in this compound.
The calculations of relative energies of the possible conformers of studied compounds
(B3LYP/6-31G* method) corresponded to obtained experimental data completely. The conformers
with axial orientation of the P=Se bond (1, 2) or the lone pair of electrons at the phosphorus atom (3)
and equatorial phenyl substituent had the energy minima (ΔE = 0 kcal . mole -1 ) for all three
1,4-heterophosphinanes. The quantum chemical calculation results for phosphinanes 1-3 were in a
good agreement with experimental data (dipole moments and Kerr constants in dioxane solution)
and calculated dipole moments (vector-additive scheme).
It was determined, that chair conformation with equatorial orientation of exocyclic phenyl
substituent is preferred for 1,4-heterophosphinanes independent of the nature of second heteroatom
in six-membered phosphorus heterocycle (oxygen [1], sulfur or silicon), and the coordination state
of the phosphorus atom (P III or P IV ).
Reference
[1] Karataeva, F.Kh.; Kushnikovskaya, I.K.; Patsanovsky, I.I.; Ishmaeva, E.A. Russian J. Gen. Chem., 1991, 61 (11),
2562.
242

O-47
STEREOSELECTIVE SYNTHESIS AND INTERCONVERSIONS OF
1,9-DIAZA-3,7,11,15-TETRAPHOSPHACYCLOHEXADECANES
R.N.Naumov, a * A.A.Karasik, a A.V.Kozlov, a Sh.K.Latypov, a D.B.Krivolapov, a A.B.Dobrynin, a I.A.Litvinov, a
O.N.Kataeva, a P.Lönnecke, b E.Hey-Hawkins, b O.G.Sinyashin a .
aA.E. Arbuzov Institute of Organic and Physical Chemistry, Russian Academy of Sciences, Arbuzov str. 8, Kazan,
420088 Russian Federation. E-mail: naumov@iopc.knc.ru
cInstitut für Anorganische Chemie der Universität Leipzig, Johannisallee 29, D-04103 Leipzig, Germany. E-mail:
hey@rz.uni-leipzig.de
The first representative of 1,9-diaza-3,7,11,15-tetraphosphacyclohexadecanes [1] has been
synthesized in the course of covalent self-assembly in three-component system:
bis(mesitylphosphino)propane, formaldehyde and benzylamine. The isomeric cyclic diphosphines -
1,3,7-azadiphosphacyclooctanes [2] were formed when primary arylamines had been used in the
condensation. However, introduction of various analogues of benzylamine (chiral
α-methylbenzylamine, ortho-, meta- and para-aminomethylpiridins) into this reaction afforded a
wide row of 1,9-diaza-3,7,11,15-tetraphosphacyclohexadecanes. Only one
S(P)R(C)S(P)R(P)R(C)R(P)-stereoisomer of the corresponding optically active 1,9-diaza-3,7,11,15
-tetraphosphacyclo-hexadecanes, containing six asymmetrical atoms, was synthesized
stereoselectively from R-α-methylbenzylamines. The polydentate macrocyclic phosphino amino
pyridines, which potentially can participate in co-ordination with transition metals due to four
phosphorus and two additional nitrogen atoms of piridine group, were synthesized. Finally, a true
racemic mixture of two rac-isomers with RRRR- and SSSS-configuration of phosphorus atoms of
cage-like 1,9-diaza-3,7,11,15-tetraphosphacyclohexadecanes (Fig. 1) was obtained in
tree-component reaction of bis(mesitylphosphino)propane, formaldehyde and meta-xylylenediamine.
Interconversions between the stereoisomers of the 1,9-diaza-3,7,11,15-tetraphospha
-cyclohexadecanes were found in the solution, demonstrating a relatively high lability of the
phosphorus atom's configuration in these macrocyclic compounds in comparison with common
tertiary phosphires.
Acknowledgements: Financial support from Volkswagen Foundation, RFBR (No.
06-03-32754-a), Russian Science Support Foundation and from President’s of RF Grant for the
support of leading scientific schools (No. 5148.2006.3) is gratefully acknowledged.
Reference
1. R. N. Naumov, A. A. Karasik, O. G. Sinyashin et al, Dalton Trans., 2004, 357.
2. A.A. Karasik, R.N. Naumov et al, Z. Anorg. Allg. Chem. 2007, in press.
243
Fig.1.

O-48
REACTIONS OF PHOSPHONIC ACIDS WITH BASES IN AQUEOUS SOLUTIONS
Myund, L. A.; Lu, N; Sidorov, Yu. V., Burkov, K. A.
St. Petersburg State University, St. Petersburg, Russia
The regular trends in the change of volume in the reactions of aqueous solutions of
methanephosphonic, 1-aminoethanephosphosphonic, carboxymethahephosphonic, 1-hydroxyethane
-1,1-diphosphonic, and nitrilotris(methanephosphonic) acids with aqueous solutions of MOH (M =
Li, Na, K, Rb, Cs), tetramethyl-, tetraethylammonium and ammonium hydroxides at 25°C were
revealed. The purposed explanation accounts the acid ionization, ion neutralization and hydration,
presence of betaine forms, and formation of proton chelates [1, 2].
Specific features of reactions of ammonia with nitrilotris(methanephosphonic) acid (H6L) in
various stages of its dissociation are discussed. The revealed differences in the action of similar
additions of ammonia and strong hydroxyl-containing bases on the state of H6L and its anions in
aqueous solution are accounted for by specific features of ammonia as a base and of ammonium ion
as a product of ammonia neutralization. Volume changes resulting from protonation of the anion of
bis(tetraethylammonium) salt of H6L were determined. Protonation consts., apparent molar
volumes of the acid and its ionized forms, and vol. changes on neutralization of the acid and
protonation of its salt were calcd. Volume changes of protonation of 1-(aminoethyl)phosphonate
anion were determined. Protonation constants, apparent molar volumes of the acid and its ionized
forms, and vol. changes on neutralization of the acid and protonation of its salt were calcd. The
presence of the betaine form of the acid in solns. was detected. The rule of the constancy of the
sum of the vol. effects of the protonation and neutralization reactions was valid for conjugate
acid-base pairs of dibasic acids.
Dissocn. and alkali complex formation equil. of nitrilotris(methylenrphosphonic) acid (NTMP,
H6L) have been studied by dilatometric, potentiometrc and 31P NMR-controlled titrns. Dilatometry
indicated the formation of alkali complexes ML (M=Li,Na,K,Rb,Cs) at high pH with a stability
decreasing from Li to Cs. An efficient combination of potentiometric and NMR methods confirmed
two types of alkali metal complexes MHL and ML. Stability consts. for the equil. following
M++HL5-.dblharw. MHL4- and M++L6- dblharw. ML5-, resp., were detd.:logKNaHL=1.08(0.07),
logKKHL=0.86(0.08), logKNaL=2.24(0.03). The actual dissocn. consts. were found: (H2L4-.
dblharw. H++HL5-) pKa5+7.47(0.03) and (HL5- dblharw. H++L6-) pKa6=14.1(0.1). The
anisotropy of 31P chem. shifts of salts MnH6-nL (M=Li, Na, n=0-5) is more sensitive towards titrn.
(n) than isotropic soln. state chem. shifts.
References
1. Grossmann, G.; Burkov, K. A.; Hagele, G.; Myund, L. A.; Hermens, S.; Verwey, C.; Arat-ool, Sh. M. Inorg. Chim.
Acta 2004, 357, 797.
2. Myund, L. A.; Latysheva, V. A.; Arat-Ool, Sh. M.; Hagele, G.; Burkov, K. A. Russ. J. Gen. Chem. 2001, 71, 1384.
244

O-49
DISTINCT π BONDING CAPABILITY BETWEEN
PHOSPHINIDENE AND PHOSPHONIUM ION
Hisn-Mei Cheng and San-Yan Chu
Department of Chemistry, National Tsing Hua University, Hsinchu 30013, Taiwan
Although both phosphinidiene (RP) and phosphonium ion (R2P + ) are isoelectronic to silylenes,
theπbonding tendency of the former is rather strong that it forms planar adduct with both the stable
carbene and stable silylene((HCNH)2E,E=C and Si, denoted A and B, repectively). In contrast, the
latter forms trans-bent adducts with the two species. Therefore, the phosphinidene and
phosphonium ion are actually analogous to the carbene and silylene, respectively, in the pi bonding
capability. These results can be interpreted in terms of CGMT model and the fact that the value of
singlet-triplet energy gap of HP fragment increases significantly after the protonation(47.9kcal/mol).
The former has two open-shell p orbitals, ready to form stable double bond. The latter has a stable
lone pair, thus a significant promotion is required for the double bond formation. Listed below are
the computation results of CH2, SiH2, PH and PH2 + (X) bonding with stable carbene (A) and stable
silylene (B) to form doubly bonded compounds A=X and B=X with B3LYP/6-311G** method.
Finally, nitrene (NH) and nitrenium (NH2 + ) haveΔEST of -49.58 and -32.70 kcal/mol respectively.
Therefore both are analogous to carbene in π bonding capability, unlike the conspicuous distinction
between HP and H2P + .
A=X RAX(A o ) angle a ΔEST(X) b
A=CH2 1.352 1.57 -12.17
A=SiH2 1.926 84.99 20.16
A=PH 1.698 0.00 -32.07
A=PH2 + 1.858 83.41 15.90
245
B=X RBX(A o ) angle ΔEST(X)
B=CH2 1.698 0.11 -12.15
B=SiH2 2.219 59.19 20.16
B=PH 2.098 0.00 -32.07
B=PH2 + 2.196 84.49 15.90
a.bending angle of X from planar geometry b.E(triplet)-E(singlet) for X in kcal/mol

O-50
DIMERIZATION AND TRIMERIZATION OF PHOSPHAACETYLENE.
A MECHANISTIC STUDY
T. Veszprémi, T. Höltzl, and M.T. Nguyen
a
Department of Inorganic Chemistry, Budapest University of Technology and Economics,
Gellért tér 4, H-1521 Budapest, Hungary. Email: Tveszpremi@mail.bme.hu
b
Department of Chemistry, University of Leuven, Celestijnenlaan 200F, B-3001 Leuven, Belgium.
Email: minh.nguyen@chem.kuleuven.ac.be
Keywords: Reaction mechanism, Di- and Tri-merization, Phosphaacetylene
Phosphaalkynes play an important role in the low-coordinated phosphorus chemistry. To
understand the oligomerization of phospha-alkynes, and predict new potential targets and reaction
conditions for synthesis, we studied the C2P2H2 potential surface and all the possible dimerization
reaction channels using high-level ab initio (CCSD(T), CBS-QB3, CASSCF, CASPT2, MR-ACPF,
MR-ACPF-2) and Density Functional Theory (B3LYP).
Seventeen low energy closed-shell and five open shell phosphaacetylene dimers could be found
on the potential energy surface. Two head-to-head, one head-to-tail and three other dimerization
reaction paths were found, all with high activation barriers, suggesting that closed-shell minima are
usually kinetically stable. An open-shell head-to-head reaction path has also been found with
moderate initial barrier (95.0 kJ/mol) leading to 1,2- and 1,3-diphosphacyclobutadiene, suggesting
that polymerization of HCP and oligomerization of its derivatives have open-shell mechanism.
Formation of 1,2-diphosphacyclobutadiene is both thermodynamically and kinetically favored over
1,3-diphosphacyclobutadiene. A head-to-head reaction involving LiBr as a catalyst was also studied.
It has been pointed out that LiBr catalyse the closed-shell mechanism. All the four possible reaction
channels of this reaction yield 1,4-diphosphatriafulvene with a fairly low activation Gibbs-free
energy (44.8 kJ/mol), suggesting that this compound could be synthesized. This finding fully
supports the experimental findings.
246

O-52
BOND ACTIVATION PROCESSES IN N-HETEROCYCLIC PHOSPHINES
D.Gudat, S.Burck, I.Hajdók, F.Lissner, M.Nieger
Institut f. Anorganische Chemie, Univ. Stuttgart, Pfaffenwaldring 55, 70569 Stuttgart,Germany
N-heterocyclic phosphines I (NHP) with exocyclic hydrogen or phosphinyl substituents display a
unique weakening of the exocyclic P–H or P–P bonds, respectively, which can be rationalized in
terms of a bond/no-bond resonance (hyperconjugation) between the canonical structures Ia and Ib
with an unusually large contribution by the ionic structure Ib.1,2 We present new results
demonstrating that this effect can be enhanced to the extent of complete ionization of a P–P bond,
giving rise to isolable ionic phosphenium-phosphides (Ib, X = PR2). The unusual molecular
structures and bonding situation in these compounds will be discussed in some detail. Reports on
the study of the chemical reactivity of P-phosphinyl substituted NHPs will focus on novel
stereoselective additions to multiple bonds, and on the exploration of the use of NHPs as
organocatalysts for phosphorus-carbon cross coupling reactions.3
The concept of exocyclic bond activation will be extended to NHPs with purely organic
substituents, and first examples of reactions under specific activation of phosphorus-carbonbonds
will be communicated.
As a complement to reactions involving activation of exocyclic P-X bonds in NHPs we will
further present experimental evidence showing that selected substituents X allow to tune the
hyperconjugation interactions in the heterocyclic to induce a weakening of an endocyclic P–N bond,
thus paving the way to novel ring fragmentation reactions.
References:
[1] S. Burck, D. Gudat, M. Nieger, Angew. Chem., Int. Ed. 2004, 43, 4801.
[2] S. Burck, D. Gudat, M. Nieger, W.W. du Mont, J. Am. Chem. Soc. 2006, 128, 3946.
[3] S. Burck, D. Förster, D. Gudat, Chem. Commun. 2006, 2810.
247

O-53
DETERMINATION OF OPTICAL PURITY OF AMINOPHOSPHONATES
BY MEANS OF NMR SPECTROSCOP
E.Rudzińska
Laboratory of Structural Analysis, Faculty of Chemistry, Wrocław University of Technology, WybrzeŜe
Wyspiańskiego 27, 50-370 Wrocław, Poland
Aminophosphonic and aminophosphinic acids constitute a class of mimetics of amino acids in
which a carboxylic group is replaced by phosphonic or related functionality. Acting as antagonists
of amino acids, they inhibit enzymes involved in amino acid metabolism and thus affect a variety of
physiological processes. Therefore, they may be used in a wide range of human activity ranging
from agriculture to medicine. These compounds have already been found to act as antibacterial
agents, neuroactive compounds, anticancer drugs and pesticides. Moreover, N-protected derivatives
of aminophosphonates represent essential substrates for the synthesis of phosphorus containing
peptidomimetics. The resulting peptide isosteres contain moieties mimicking the high-energy
tetrahedral transition state of amide bond hydrolysis. Due to this feature, they constitute a class of
effective inhibitors of proteases, exhibiting particular potency towards metallo-dependent enzymes.
It is well recognized that the biological activity of organic compounds is strongly dependent on
their stereochemistry. Thus, a simple and versatile method for determination of optical purity of
these compounds is strongly desirable. Here, we summarize the application of 31P NMR
spectroscopy as a fast, versatile and reliable technique for enantiodiscrimination of a wide group of
aminophosphonic, aminophosphinic acids, their N-benzyloxycarbonyl derivatives as well as
phosphonate ethyl and phenyl monoesters. Different commercially available cyclodextrins and
O-tertbutylcarbamoylquinine and quinidine were successfully applied as chemical shift reagents.
Employing two-dimensional NMR techniques selected ligand-receptor complexes were studied
in some details. Molecular modelling studies of the interaction within the supramolecular structures
were performed as well.
248

O-54
PHOSPHORUS STABILZES AND CAN BE STABILIZED
László Nyulászi
Department of Inorganic Chemistry Budapest University of Technology and Economics
H-1521 Budapest Szt Gellért tér 4, Hungary
nyulaszi@mail.bme.hu
The covalent bonds in the chemistry of phosphorus-carbon compounds exhibit a great diversity,
including single, double, triple bonds with or without the expansion of the valence shell. In the
present contribution some examples will be presented where these well known bonding structures
are perturbed by substituents, and as a result the stability of unusual compounds can be predicted.
To quantitize the effects we use a computational approach, calculating isodesmic reactions. Both
the thermodynamics and the kinetics of possible dimerization and oligomerization reaction will be
investigated by calculating the energies and barriers of these processes. The computed results are
compared to the available experimental observations.
It will be discussed in detail, which substituents stabilize phosphorus effectively in
phosphinidenes.1 Also the stabilizing effect of a pair of phosphorus lone pairs will be discussed in
case of carbocations2 and carbenes, in relation with the inversion barrier at the tricoordinate
phosphorus. Further stabilizing and destabilizing effects will be discussed in case of phosphole.3
Reference
1. Z. Benkő, R. Streubel, L. Nyulászi Dalton Transactions 2006, 4321.
2. M. Sebastian, A. Hoskin, M. Nieger, L. Nyulászi, E. Niecke Angew. Chem. 2005, 44, 1405.
3. L. Nyulászi, O. Hollóczki, C. Lescop, M. Hissler, R. Reau Org. Biomol. Chem. 2006, 4, 996.
249

O-94
MECHANISM OF AMINO ACIDS MEDIATED OLIGOMERIZATION INTO PEPTIDES
BY PHOSPHORUS TRICHLORIDE
W.J.Zhao 1 D.X.Zhao 1 K.Lu 1*
1.School of Chemistry and Chemical Engineering, Henan University of Technology, Zhengzhou 450052, China;
2.Department of Chemistry, Xiamen University, Xiamen 361005, China
N-phosphoryl a-amino acids and N,O-bis(trimethylsilyl)-a-amino acids could self-activated to
give peptides and the reaction mechanism undergo penta-coordinate phosphorus intermediate of
amino acid[1]. In our previous work with the assistance of inorganic phosphorus amino acids also
could be assembled into oligopeptides[2,3]. In this paper, the reaction mechanism was studied by
using 31P NMR and electrospray ionization mass spectrometry(ESI-MS/MS). Based on the results
obtainted by 31 P NMR and ESI-MS/MS, a detailed reaction mechanism of peptidesformation from
amino acid mediated by phosphorus trichloride was proposed. Aminoacyl-phosphorus trichloride
mixed anhydride and N-phosphoryl a-amino acids were produced by amino acids reacting with
phosphorus trichloride. A penta-coordinated phosphorus intermediated was formed via an
aminoacyl-phosphorus trichloride mixed anhydride or N-phosphoryl a-amino acids. The carbonyl
group of the penta-coordinated phosphorus intermediated was activated and then was attacked by an
amino acid to yield N-phosphoryl dipeptide and loss one hydroxyl phosphorus oxychloride
molecule. If dipeptide reacts with the penta-coordinated phosphorus intermediated tripeptide will
produced following the same way. The formation of longer peptides may be deduced by analogy.
However, the penta-coordinated phosphorus intermediated is un stable and only exists as
instantaneous intermediated. There is no signal of penta-coordinated phosphorus intermediated
appeared in the stack 31P NMR spectra. But the progress of N,O-bis(trimethylsilyl)-a-amino acids
reacting with phosphorus trichloride in dichloridemethane was monitored and the signal of
penta-coordinated phosphorus intermediated appeared in 31P NMR spectroscopy.
References
[1] Y. Ju, Y. F. Zhao, Y. W. Sha, et al, Phosphorus, Sulfur and Silicon. 1995,101(1-4): 117
[2] H. Li, W. J. Zhao, S. X. Cao, et al. Chem. J. Chinese Universities, 2004, 25, 1866.
250

P-103
MECHANISM OF AMINO ACIDS MEDIATED OLIGOMERIZATION INTO PEPTIDES
BY PHOSPHORUS TRICHLORIDE
Wenjie Zhao, Dongxin Zhao, Kui Lu*
School of Chemistry and Chemical Engineering, Henan University of Technology, Zhengzhou 450052, China
N-phosphoryl-amino acids and N,O-bis(trimethylsilyl)- -amino acids could self-activated to
give peptides and the reaction mechanism undergo penta-coordinate phosphorus intermediate of
amino acid [1]. In our previous work with the assistance of inorganic phosphorus amino acids also
could be assembled into oligopeptides [2,3] . The reaction mechanism was studied by using 31 P NMR
and electrospray ionization mass spectrometry (ESI-MS/MS).
Based on the results obtainted by 31 P NMR and ESI-MS/MS, a detailed reaction mechanism of
peptides formation from amino acid mediated by phosphorus trichloride was proposed.
Aminoacyl-phosphorus trichloride mixed anhydride and N-phosphoryl -amino acids were
produced by amino acids reacting with phosphorus trichloride. A penta-coordinated phosphorus
intermediated was formed via an aminoacyl-phosphorus trichloride mixed anhydride or
N-phosphoryl -amino acids. The carbonyl group of the penta-coordinated phosphorus
intermediated was activated and then was attacked by an amino acid to yield N-phosphoryl
dipeptide and loss one hydroxyl phosphorus oxychloride molecule. If dipeptide reacts with the
penta-coordinated phosphorus intermediated tripeptide will produced following the same way. The
formation of longer peptides may be deduced by analogy. However, the penta-coordinated
phosphorus intermediated is unstable and only exists as instantaneous intermediated. There is no
signal of penta-coordinated phosphorus intermediated appeared in the stack 31 P NMR spectra. But
the progress of N,O-bis(trimethylsilyl)- -amino acids reacting with phosphorus trichloride in
dichloridemethane was monitored and the signal of penta-coordinated phosphorus intermediated
appeared in 31 P NMR spectroscopy.
Acknowledgements: The authors would like to thank the financial supports from the Chinese
National Science Foundation (No.20272055, 20572016), Henan Province Science Foundation for
Prominent Youth (No.0312000900) and Office of Education of Henan Province (No.
2006KYCX017).
References:
1. Y. Ju, Y. F. Zhao, Y. W. Sha, et al, Phosphorus, Sulfur and Silicon. 1995,101(1-4): 117-123
2. H. Li, W. J. Zhao, S. X. Cao, et al. Chem. J. Chinese Universities, 2004, 25, 1866.
3. Zhou N.; Lu K.; Liu Y. et al. Rapid Commun. Mass Spectrom. 2002,16,919.
251

P-137
CAN FOUR MEMBERED HETEROPHOSPHETE STRUCTURES EXIST?
“HETEROGEN” HETERO ANTIAROMATICITY AS A DESTABILIZING EFFECT
Zoltán Mucsi, 1 Tamás Körtvélyesi, 2 Tibor Novák 3 , György Keglevich 1
1 Department of Organic Chemical Technology, Budapest University of Technology and Economics
H-1521 Budapest, Hungary
2
Department of Physical Chemistry, University of Szeged, H-6701 Szeged, Hungary
3
Research Group of the Hungarian Academy of Sciences at the Department of Organic Chemical Technology, BUTE,
H-1521 Budapest, Hungary
Four-membered heterophosphetes (Figure 1), existing as two conformers (1A and 1B) are
thermodynamically unstable and they readily undergo ring-opening reactions to form oxo-, imino-
or thiaphosphoranes 3 [1]. This may be one of the reasons that earlier synthetic attempts to produce
heterophosphetes have mostly failed. Their saturated counterparts heterophosphetanes (2A and 2B),
which are well-known intermediates of the Wittig reaction are, however, stable and cannot undergo
ring-opening reaction. The question arises, what the reason for this sharp difference is between the
stability of 1 and 2.
Our results based on quantum chemical calculations revealed, that the instability of 1A and 1B
should be attributed to their antiaromatic character, originated form the conjugation of the empty
d-orbitals of the P atom and the occupied pz orbital of the Y moiety. This type of antiaromaticity is
defined as a “heterogenic” antiaromaticity. Compounds 1A with equatorial Y possess a more
considerable extent of antiaromatic character, than species 1B with axial Y, which practically can
be considered as non-aromatic compounds. It has been shown, that strong electron withdrawing
substituents (F, Cl, CN) bound to the phosphorus atom are able to stabilize the ring system. The
thermodynamic stability of 1A and 1B has been studied systematically and the extent of
antiaromaticity of these species was quantified by a linear aromatic and antiaromatic scale (Figure
2). An overall 3D potential surface, as well as an antiaromaticity % surface of 1 have been
discovered.
X
Y P
X
X
1A
1B
Equatorial Y Apical Y
X
Y P
2A
X
X
X X
X X
Y P X Y P X
XX
X X
Y P X Y P X
X = F, Cl, CN
Y = O, NH, S
Figure 1. Transformations of heterophosphetes (1A
and 1B) and heterophosphetanes (2A and 2B)
2B
3
4
1B
1A
252
NH,F
NH,Cl
NH,CN
O,F
O,Cl
O,CN
S,F
S,Cl
S,CN
NH,Cl
S,F
O,F
non-aromatic
character
S,Cl
O,Cl
O,CN
S,CN
-40 -35 -30 -25 -20 -15 -10 -5 0 5 10 15
antiaromaticity % aromaticity %
Reference
[1] Gy. Keglevich, H. Forintos, T. Körtvélyesi, Current Org. Chem. 8, 1245 (2004).
NH,F
Figure 2. Computed aromaticity and antiaromaticity
scale for 1A and 1B
NH,CN

P-155
SYNTHESIS AND MECHANISM STUDIES ON AMIDE BOND BY
HEXAMETHYLPHOSPHORAMIDE(HMPA)
Jianbo Hou 1 , Tongjian Wang 1 , Kan Lin 1 , Guo Tang 1 , Yufen Zhao 1,2
1 Department of Chemistry, The Key Laboratory for Chemical Biology of Fujian Province, College of Chemistry and
Chemical Engineering, Xiamen University, Xiamen 361005, P. R. China; 2 The Key Laboratory of Bioorganic
Phosphorus Chemistry, Department of Chemistry, School of Life Science and Engineering, Tsinghua University,
Beijing 100084, P. R. China
Recently, organic phosphorous coupling reagents (eg. triphenylphosphine) have been applied
for the synthesis of peptide derivatives [1-3]. In this paper HMPA was used as amide bond coupling
reagent, and the mechanism was studied.
Triphosgene was dissolved in solvent and was added dropwise to a mixed solution of
carboxylic acid and HMPA at 0 ℃, the phosphinic carboxylic mixed anhydride was formed. And
then the above solution was added dropwise to the amine solvent at 0 ℃. The amide bond was
formed. After extraction, HMPA could be recycled.
The reaction was traced by 31 P NMR(Figure 1).
O
P
N N N
+ R
Cl
1COOH O
C
a b
R1 =-CH3 ,-C6H5 Cl
Cl
O
C O
P Cl
N N
N
Scheme 1.
253
O
R
O
2NH2 P
R2NH C + N N + HCl
N
R 1
R 2 =-CH 2 C 6 H 5 ,-C 6 H 5 ,-CH 2 CH 2 CH 2 CH 3
Figure 1: The Stack 31 P NMR Spectra of Synthesis amide bond
a:Hexamethylphosphoramide; b:phosphinic carboxylic mixed anhydride;
c:Hexamethylphosphoramide (recycled) .
Project was supported by NNSFC (No. 200572061)
References
[1] Appel R.,Roland M., Chem. Ber., 1977, 110, 2385.
[2] Appel R., Heinfried S., Chem. Ber., 1977, 110, 2382.
[3] Tang G., Zhou G. J., Zhao Y.F., Chin. Chem. Lett., 2005, 16(3), 385-388.
b
a
c
RNH 2 in Solvent was Dropwised
C 3Cl 6O 3 in Solvent was Dropwised
Solvent and HMPA and RCOOH
c

P-163
INTERACTION OF 2H-1,2,3-DIAZAPHOSPHOLE WITH DIOLS
*M.A.Khusainov, R.A.Cherkasov, N.G.Khusainova, , O.A.Mostovaya, *I.F.Gataulina
Kazan State University, Kremlevskaya str.18, Kazan, 420008,Russia;
*Kazan State Technological University, K.Marks str.68, Kazan, 420015, Russia
e-mail:narkis.khusainova@ksu.ru
The heterocyclic derivatives of two-coordinated phosphorus containing σ2 λ3 –P=C bond
interaction with diols has been studied.. We have found (by kinetic 31P NMR spectroscopy) that the
reaction of 5-methyl-2-phenyl-2H-1,2,3- diazaphosphole 1 with catechol 2 furnishes a mixture of
tautomeric diazaphospholene 3 and hidrospirophosphorane 4. At increasing temperature fill
room temperature the 3 and 4 adducts undergo fragmentation into phenylhydrazone acetone 5,
symmetric hydrospirophosphorane 6 and phosphite 7 .
Ph
N
P N
+
H
N
Ph N
OH
OH
N
N
Ph
P
O
O O
P
O O
H
6
254
OH
N
Ph
N
P H
O O
1 2
3
4
5
+
Reaction of 2-acetyl-5-metyl-2H-1,2,3-diazaphosphole with (rac)butane-2,3-diol at temperature
below 0oC leads to formation of asymmetrical compounds: hydrospirophosphorane containing
both diazaphospholene and dioxaphospholane ring system and 1,2,3-diazaphospholene. Then its
interconversion results in fragmentation of the diazaphospholene ring in these compounds with the
formation of the symmetrical hydrospirotetraoxaphosphorane, β-hydroxyphosphite, hydrazone and
symmetrical bisphosphite as the main products [1]. Termodynamical stability of all these reaction
members was analysed by calculation using methods of quantum chemistry (PM3 and
HF/6-31G(d,p) methods) for the first time. Instability of the hydrospirophosphorane and the
1,2,3-diazaphospholene is confirmed by quantum chemical calculations. On the basis of
thermodynamical characteristics initialy formed products are less expedient in comparison with
symmetrical hydrospirotetraoxaphosphorane, its tautomer and symmetrical bisphosphite.
Calculations confirm that tautomeric equilibrium in tri- and penta-coordinated phosphorus is shifted
towards the hydrospirophosphorane. Response mechanism as nucleophilic 1,2-addition of diol to
P=C bond was inferred from preliminary calculation and analysis of charge density in atoms of
reactive center. Oxiorganical group attacks atom of two-coordinated phosphorus regioselectively
with increasing in phosphorus coordination.
+
O
P O
O
Rererence
1. Khusainova N.G., Mostovaya O.A., Azancheev N.M., et.al., Mend. Comm. 2004, N5, P. 2
7

P-169
LOCATING THE REACTION PATHS OF N-(DIALKYLOXYPHOSPHORYL) AMINO
ACIDS BY NUDGED ELASTIC BAND(NEB) METHOD
NI, F.; Zeng, Z. P.; Zhao, Y. F *
Key Lab of Chemical Biology of Fujian Province, Department of Chemistry, Xiamen University, Xiamen, 361005,
China
N-(dialkyloxyphosphoryl)amino acids(NPAAs) are active compounds which can undergo many
important reactions such as peptide formation, esterification, phosphoryl group transfer, hydrolysis
et al. in mild water/alcohol solution 1 . NPAAs with different amino acid side chains show different
reactivity remarkably and it was testified that a penta-coordinated intermediate plays an important
role during above reactions 2 . Hence, theoretical examination of reaction paths between NPAAs and
their intermediates are of great interest. An efficient and successful method for obtaining the
reaction paths is one known as “nudged elastic band” (NEB) 3 . In this work, 9
N-(dimethyloxyphosphoryl) amino acids (A,F,G,I,L,V,W, Y,M) models were studied by NEB
method implemented in Dynamo 4 with AM1,PM3,MNDO and PDDG 5 respectively and the results
were compared with those by Berny method implemented in Gaussian03 6 with DET at
6-31G(d,p)level.
The calculation shows that (i) NEB method(with AM1 or MNDO ) gave good energy profiles
along the reaction paths between NPAAs and their intermediates.(see Figure) (ii)Transition state
structures alone the reaction paths found by NEB method with AM1 are well close to those found
by Berny method implemented in Gaussian03 with DET at 6-31G(d,p) level.
Energy
(kJ/mol)
MeO
MeO
O
P
MeO
MeO
O
P
H
N CH C
NPPA
H
TS
R
O
H
N
O
H
O
R
OH
255
HO
MeO
Reaction coordinate (Ǻ)
O
P
OMe
O
N
H
H
R
Intermediate
Figure Reaction paths between NPAAs and their penta-coordinated intermediates located
by NEB method with AM1 ( Data of F,I,W not show here, DMP:
dimethyloxyphosphoryl group, Y,V, M, L, G, A, F, I, W: single letter abbreviation

Reference
1. Cheng, C. M.; Liu, X. H.; Li, Y. M.; Ma, Y.; et al.Origins of Life and Evolution of the Biosphere 2004, 34 (5), 455
2. Fu, H. ; Li, Z. L. ; Zhao,Y. F. ; et al. Journal of The American Chemical Society 1999, 121 (2), 291
3. Jónsson,H.; Mills, G.; Jacobsen, K.W.; in Classical and Quantum Dynamics in Condensed Phase Simulations, ed.
Berne, B.J.; Ciccotti, G.; Coker, D.F. World Scientific, 1998
4. Field, M. J.; Albe, M.; Bret, C.; et al. Jounal of Computational Chemistry 2000, 21(12), 1088.
5. Repasky, M. P.; Chandrasekhar, J; Jorgensen; W. L. Jounal of Computational Chemistry 2002, 23(16), 1601
6. Gaussian 03, Revision C.02 Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.et al, Gaussian, Inc., Wallingford CT,
2004.
256

P-194
THE FORMATION MECHANISM OF THE α-HYDROXYPHOSPHONATE: A
THEORETICAL STUDY
Zeng Zhiping Fang Hua Zhao Yufen*
The Key Laboratory for Chemical Biology of Fujian Province, Department of Chemistry, Xiamen University, Xiamen
361005, China. E-mail: yfzhao@xmu.edu.cn
α-hydroxyphosphonate, showing definite bioactivities, are a useful intermediate for many
organophosphorus derivative. But its formation mechanism is unknown until now. In our lab, we
have synthesize a lot of α-hydroxyphosphonates and they are all meso, so how to control the charity
of the α-hydroxyphosphonate is very crucial. The mechanism may answer this question for us, and a
detail study is carrying out.
A simple theoretical model of our reaction is shown below.(study reaction).and one of the
DFT method (b3lyp) is applied to capture the transition state. All the calculation is based on
6-311g* basis set .
O
O
1.654
study reaction:
O
P
HO H OH
1.654
P
O
1.615
O
O P 1.463
1.615
1.410
0.970
1.644
O
BASE
BASE
E(kcal.mol-1 Δ
)
117.2
reactant
OH
P
HO OH
10.21
0.4
4TS
5TS
257
O
C
H H
four-ring TS
139.9
fast
32.32
product
1.637
unfavorable
five-ring TS
favorable
O OH
HO P C H
OHH
O
O
2.072
C
P
O
O
1.631
O
1.606
1.016
P
2.082
1.518
1.557
1.345
O
1.569
O
1.450
1.445
O
C
1.298
TS
O
1.624
O
1.610
P
1.482
1.827
1.087
C 1.416
O
1.097 0.966
O
O
H O
P H
H
H
O
C O
H
O
H
O
H
H
H
OH
HO
H
H
P O
H
C O
P
O
C OH
The QM study result shows that: the reaction pathway may encounter an interconversion from
four-coordinate to three-coordinate phosphorus. And then a five-ring transition state is formed to
reduce the activative reaction energy greatly(100kcal.mol-1). Also, the experiment will be designed
to check our suppose later on.
Reference
[1]. M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria,M. A. Robb, J. R. Cheeseman, J. A. Montgomery, Jr., T.
Vreven, Gaussian, Inc., Wallingford CT, 2004.

P-182
31 P NMR ASSAY OF THE ENANTIOMERIC EXCESS BY USING QUININE AS CHIRAL
SOLVATING AGENT
Liu Ruoyu 1 , Ye Yong 1 , Chen Xiaolan , Liao Xincheng 1 , Zhao Yufen 1,2
(1.The Key Laboratory of Chemical Biology and Organic Chemistry of Henan Province, Department of Chemistry,
Zhengzhou University, Zhengzhou 450052, China;
2.The Key Laboratory for Bioorganic Phosphorus Chemistry and Chemical Biology, Ministry of Education, Department
of Chemistry School of Life Sciences and Engineering, TsinghuaUniversity, Beijing 100084, China)
Phosphonates and phosphonic acids have become increasingly important due to their diverse
and useful biological properties with possible applications ranging from medicine to agriculture.
But the lack of simple and accurate methods for the determination of enantiomeric excess is
currently the main problem in designing stereocontrolled syntheses for such as compounds.We
recently are engaged in exploring methods for the asymmetric synthesis of some phosphonates and
establishing a reliable method for the determination of enantiomeric purity , enantiomeric excess
and absolute configuration.
31 P NMR spectroscopy is a very convenient tool for determination of the enantiomeric excess of
organophosphorus compounds because of the large chemical dispersion and the simplicity of the
broad band 1 H decoupling spectra.
High quality 31 P NMR spectrum, for determation of the enantiomeric excess of phosphonate
esters, was obtained by using quinine as a chiral solvating agent.
The molar ratio of phosphonate esters :quinine varise from 1:0.5 to 1:7. It was found that the best
result could obtained in ratio 1:1. Maybe other factors such as temperature, time still need to be
invested for better results.
For the chiral solvating agent is expensive ,we also try to find some appropriate methods to
recycle it.
Fig. 31 P NMR spectrum of a chiral
organophosporus in the presence of
quinine.
References
[1] Alina Maly, Barbara Lejczak and Pawel Kafarski :Tetrahedron: Asymmetry 14 (2003) 1019–1024
258

Symposium 6
Phosphorus Compound and Medicinal Chemistry

KL-9
A CORRELATION OF ANTIRESORPTIVE STRUCTURE ACTIVITY RELATIONSHIPS
IN NITROGEN-CONTAINING BISPHOSPHONATES CO-CRYSTALIZED IN FARNESYL
DIPHOSPHATE SYNTHASE SUGGESTS THEIR BINDING MODE
F. H. Ebetino* 1 , B. L. Barnett 4 , B. A. Kashemirov 2 , C. Roze 2 , C. E. McKenna 2 , J. Hogan 2 , A. G. Evdokimov 3 , M. E.
Pokross 3 , J. Dunford 5 , Z. Xia 5 , K. Kavanagh 5 , R. G. G. Russell 5
1New Drug Development, Procter and Gamble Pharmaceuticals, Mason, 2Chemistry Department, University of
Southern California, Los Angeles, CA, 3New Drug Development, Procter and Gamble Pharmaceuticals, Mason, OH,
4Chemistry Department, University of Cincinnati, Cincinnati, OH, United States, 5Botner Research Centre, Oxford
University, Oxford
Investigations continue to better understand the precise mechanism of action of bisphosphonates
that contributes to their ability to be utilized as excellent therapies for metabolic bone diseases such
as osteoporosis. Both the biochemical and mineral targets and structure-activity relationships are
being established. Farnesyl diphosphate synthase (FDPS) is a metabolic enzyme that has been
demonstrated to be a major molecular target of nitrogen-containing bisphosphonates (N-BPs). It has
been known for many years that minor changes to the structure of N-BPs can dramatically affect
their antiresorptive potency. However, a detailed explanation has been lacking. Progress on the
generation of co-crystal structures of this enzyme in the presence of several potent and weak N-BP
inhibitors has provided an opportunity to examine the precise way in which bisphosphonates act on
FDPS. The active site of FDPS contains two substrate binding sites (for GPP/DMAPP and for IPP).
The current protein crystallographic evidence shows that risedronate and zoledronate occupy the
GPP/DMAPP site in a very similar manner correlating with their very potent enzyme inhibition
(IC50’s 4.1, 5.7 nM respectively). Other clinically relevant bisphosphonates such as alendronate, and
ibandronate seem to occupy this site in a less optimal manner (IC50’s 325, 23 nM respectively). We
have therefore begun to investigate whether wide ranging inhibitory potency differences observed
among N-BPs in vivo and as inhibitors of the human enzyme can be explained by key interactions
within the GPP/DMAPP site.
Additional co-crystal data on several potent and weakly active N-BPs have been assigned. These
structures all closely compare with the PCP binding characteristics of risedronate. Also, key
interactions of the critical nitrogen residue with Threonine 201 –OH and the Lysine 200 backbone
C=O were observed with all potent N-BPs exhibiting appropriate NHO angle of greater than 125
degrees and a N-O distance of 3.1A or less. However, the weakly active N-BPs, NE-11809 and NE
58051, NE58086 display longer N-O distances of 7.01A, 4.58A, and 4.28 respectively, explaining
their lack of activity. Furthermore, we have successfully predicted these binding modes utilizing
computational modeling techniques. Additional active analogs were also studied. Thus, NE-11808,
NE-11807 and NE-58025 exhibited similar H-bonding characteristics involving the nitrogen of the
N-BP. Comparative analyses of structurally and clinically relevant N-BP’s is now possible with
these techniques. With the correlations observed, the GPP site and the accessibility of these
hydrogen bonding sites to the nitrogen moiety is further established as a key explanation for the
differences in potency of N-BPs. These data also suggest contrasting 3-D structural requirements
for the biochemical effects of the nitrogen containing bisphosphonates vs the shape and orientation
necessary for these agents to exhibit high bone mineral affinity.
259

KL-10
SPECIFICITY OF PHOSPHOTHREONINE RECOGNITION BY FHA DOMAINS
Ming-Daw Tsai
Institute of Biological Chemistry and Genomics Research Center, Academia Sinica, Taiwan, and Ohio State University,
Columbus, Ohio, USA
Recently a phosphorylation-dependent recognition domain, known as forkhead-associated (FHA)
domain, has been shown to mediate protein-protein interactions in many cellular processes of
different species. While the sequence homology of FHA domains is relatively low (∼ 20%),
several tertiary structures solved in our lab reveal a remarkably similar folding, consisting of
-strands linked by several loops to form two large twisted antiparallel -sheets folded into a
-sandwich.
A wealth of information on the ligand specificity of FHA domains has been obtained by use of
short phosphopeptides and phosphopeptide libraries consisting of 6-15 residues. These studies
with short phosphopeptides showed that, while the Rad53 FHA1 domain specifically recognizes the
phosphothreonine peptides containing Asp at +3 position (pTXXD), the Rad53 FHA2 domain is
able to bind both Thr- and Tyr-phosphorylated peptides containing a hydrophobic amino acid at +3
and +2 position (pTXXL/I and pYXL/I), respectively.
Interestingly, unlike other FHA domains, the ligand recognition by human Ki67 FHA domain is
not dictated by any of the conserved motifs mentioned above, but involves an extended binding
surface. The FHA domain of human Ki67 interacts with hNIFK, recognizing a 44 residue
fragment, hNIFK(226-269), phosphorylated at T234. Here we show that high affinity binding
requires sequential phosphorylation by two kinases, CDK1 and GSK3, yielding pT238, pT234, and
pS230. We determined the solution structure of Ki67FHA in the complex with the triply
phosphorylated peptide hNIFK(226-269)3P, revealing not only local recognition of pT234 but
also the extension of the -sheet of the FHA domain by the addition of a -strand of hNIFK. The
present structure represents an important complex of an FHA domain with a biologically relevant
binding partner, provides novel insight into ligand specificity and potentially links the cancer
marker protein Ki67 to a signaling pathway associated with cell-fate specification.
Reference
1. “Structure and Function of A New Phosphopeptide Binding Domain Containing the FHA2 of Rad53” by Hua Liao,
In-Ja L. Byeon, and Ming-Daw Tsai, J. Mol. Biol. 294, 1041-1049 (1999).
2. “FHA Domain-Ligand Interactions: Importance of Integrating Chemical and Biological Approaches”. Anjali
Mahajan, Chunhua Yuan, Brietta L. Pike, Jorg Heierhorst, Chi-Fon Chang, and Ming-Daw Tsai, J. Am. Chem. Soc. 127,
14572-14573 (2005).
3. “Sequential Phosphorylation and Multisite Interactions Characterize Specific Target Recognition by the FHA
Domain of Ki-67”, by In-Ja L. Byeon, Hongyuan Li, Haiyan Song, Angela M. Gronenborn, and Ming-Daw Tsai,
Nature Structural and Molecular Biology 12, 987-993 (2005).
260

KL-18
PHOSPHONATE ANALOGS FOR DRUG DESIGN
C. E. McKenna 1 *, B. A. Kashemirov 1 , T. G. Upto n1 , L. W. Peterson 1 , J. Bala, K. M. Błażewska 1 , C. Sucato 1 , M. F.
Goodman 1 , S. H. Wilson 2 , L. C. Pedersen 2 , F.H. Ebetino and J. M. Hilfinger 3
1 Department of Chemistry, University of Southern Calif., Los Angeles, CA 90089 USA
2 Laboratory of Structural Biology, NIEHS, Research Triangle Park, NC USA 27709
3 TSRL, Inc., Ann Arbor, MI 48108 USA
Phosphonate analogs mimicking naturally occurring biophosphates are useful tools for probing
enzyme structure and function, providing insights that can inform drug design. Three examples will
be given, based on recent work in our laboratory. 1) DNA polymerase β is a key DNA repair
enzyme that is a potential new target for antineoplastic drugs. To examine leaving-group effects on
the nucleotidyl transfer mechanism and fidelity of DNA polymerase β, we synthesized a series of
β,γ-CXY bisphosphonic acid analogs of dGTP, in which X, Y = H, F, Cl, Br or Me. Structural
evidence suggests that the analogues bind in essentially the native conformation, making them
suitable substrates for probing linear free energy relationships (LFERs) in transientkinetics
experiments. In addition, docking experiments together with crystal structure studies of a ternary
complex of DNA pol β with a primer, template and β,γ-CHF dGTP suggest that a fluorine-hydrogen
bridging interaction within the dNTP binding pocket contributes to stereospecific binding of one of
the two β,γ-CHF diastereomers. 2) Synthesis, and characterization of new analogs of
bisphosphonates effective in bone disease will be discussed. 3) The synthesis and preliminary
evaluation of stereoisomeric depeptide prodrugs of cidofovir (HPMPC) a broad-spectrum antiviral
agent that is used to treat AIDS-related CMV retinitis, will be described. These analogs permit an
assessment of peptide stereochemistry on prodrug transport and activation to parent drug.
261

KL-20
CHIRAL FUNCTIONALIZED PHOSPHONATES WITH BIOLOGICAL SIGNIFICANCE
Chengye Yuan
State Key Laboratory of Bio-organic and Natural Products Chemistry,
Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences.
Shanghai 200032, China.
As a class of organic molecules with potential biological activities, functionalized phosphonates
aroused interests of organic chemists working on the medicinal and allied fields. In the first part of
this paper, asymmetric synthesis of amino-phosphonic acids based on 1,2- and 1,3-H migration was
demonstrated. Both difluoro- and trifluoromethylated counterparts were also reported. Our recent
attention is focused on the chemoenzymatic approach to title compounds. In addition to the
structural effect of substract on bio-catalytical reduction by baker’s yeast, we have also developed a
Candida Antarctica Lipase B (CALB)-catalyzed acetylation as well as Candida rugosa Lipase
(CRL)-catalyzed hydrolysis in organic media in combination with immobilized mucormichei (IM)
mediated hydrolysis for the preparation of optically pure hydroxyalkylphosphonates and their
derivative. A group of biologically active phosphorus compounds including phosphocarnitine,
phosphogabob and fosfomycine was prepared. Dynamic kinetic resolution (DKR) was studied in
the enzymatic resolution of functionalized phosphonates. Both entiomers of
2-oxo-4-hydroxy-4-alkyl/aryl alkane phosphonates prepared by enzymatic method are converted
catalytically to chchiral 2-phosphoryl-3-oxo-5-alkyl/aryltetrahydrofuranes by Rhodium acetate via
intramolecular O-H insertion reaction. The presence of β-ketophosphonate skeleton in these
heterocyclics allowed this cyclic Hornor-Wadswath-Emmons reaction with aldehyde to furnish
chiral α,β-unsaturated ketone, a new class of building block in organic synthesis.
Acknowlegements: The Project was supported by National Natural Science Foundation of China.
(20372076, 20672132)
262

IL-19
STEREOCONTROLLED SYNTHESIS OF PHSOPHOROTHIOATE DNA AND RNA BY
THE OXAZAPHOSPHOLIDINE APPROACH
Takeshi Wada
Department of Medical Genome Sciences, Graduate School of Frontier Sciences,The University of TokyoBioscience
Building 702, 5-1-5 Kashiwanoha, Kashiwa 277-8562, Japan Tel: +81-4-7136-3612, Fax: +81-4-7136-3612,
E-mail: wada@k.u-tokyo.ac.jp
In recent years, a great deal of attention has been focused on small DNA and RNA molecules as
therapeutic agents for selective inhibition of gene expression. [1] Oligonucleotide therapeutic agents,
such as antisense DNAs, ribozymes, and siRNAs act on a target mRNA and arrest the protein
synthesis. In order to stabilize these molecules in cells, a chemical modification of internucleotidic
phosphodiester bonds is quite effective. Phosphorothioate DNA is one of the most widely used
backbone-modified antisense DNAs. [2] However, the currently used phosphorothioate DNAs are
random mixtures of diastereomers since the chirality of the phosphorous atom cannot be controlled
by use of the current synthetic methods. [3] Because the properties of phosphorothioate DNAs, such
as hybridization abilities with mRNA, affinities to proteins, and tolerances against nucleases are
considered to be affected by the chirality of the phosphorous atoms, it is an important subject to
develop an efficient method for obtaining stereoregulated phosphorothioate DNAs. Quite recently,
we have developed a novel approach for the stereocontrolled synthesis of phosphorothioate DNAs
and RNAs by the use of nucleoside 3’-O-oxazaphospholidine derivatives as monomers and
N-(cyanomethyl) ammonium salts as activators (oxazaphospholidine approach). [4-12] In this paper, I
wish to describe a recent progress of stereocontrolled synthesis of P-chiral DNA and RNA analogs,
which are useful as oligonucleotide therapeutic reagents, by the oxazaphospholidine approach.
An oxazaphospholidine approach for the stereocontrolled synthesis of phosphorothioate DNAs
and RNAs is outlined in Scheme 1. Properly protected nucleosides 1 were allowed to react with
cyclic phosphorochloridite derivatives 2 to give the corresponding nucleoside 3’-cyclic
phosphoramidite monomers 3 in good yields with high diastereoselectivities. The stereoselectivity
of the reaction was found to be highly dependent on the nature of the substituent groups (R 1 , R 2 , and
R 3 ) on the oxazaphospholidine ring of 2. Thus obtained diastereopure nucleoside 3’-cyclic
phsophoramidites 3 were condensed with nucleosides 4 bearing the free 5’-OH in the presence of an
263

acid activator. When N-(cyanomethyl)pyrrolidinium triflate (CMPT) was employed as an activator,
the condensation reaction proceeded smoothly and gave the corresponding dinucleoside phosphite
intermediate 5 with excellent diastereoselectivity. In contrast to this fact, the condensation in the
presence of a conventional activator, 1H-tetrazole, proceeded very slowly with low
diastereoselectivity. After successive N-acetylation and P-sulfurization, the diastereopure fully
protected dinucleoside phosphorothioates 6 were obtained in good yields. Finally, all of the
protecting groups were removed by a conventional procedure to give the diastereopure dinucleoside
phosphorothioates 7 in good yields. The present methodology was also applied to the solid-phase
synthesis of stereoregulated phosphorothioate DNAs. The diastereopure phosphorothioate DNAs
(4–10mer) were obtained in good yields. Work on the solid-phase synthesis of phosphorothioate
RNAs is now in progress.11 This approach would be applicable to the synthesis of various P-chiral
oligonucleotide analogs other than phosphotothioates such as boranophaosphate DNA. [13,14] Further
studies are now underway in this direction.
References
[1]. Therapeutic Oligonucleotides; Cho-Chung, Y. S.; Gewirtz, A. M.; Stein, C. A.; New York Academy of Sciences:
New York, 2004; and references therein.
[2]. Levin, A. A. Biochim. Biophys. Acta 1999, 1489, 69-84.
[3]. Zon, G.; Stec, W. J. In Oligonucleotides and Analogues: A Practical Approach; Eckstein, F., Ed.; IRL Press: Oxford
University, 1991; pp 87-108. Zon, G., In Protocols for Oligonucleotides and Analogs, Methods in Molecular Biology,
Vol. 20, Agrawal, S., Ed.; Humana Press: Totowa, New Jersey, 1993; pp 165-189.
[4]. Oka, N., Wada, T., Saigo. K. Nucleic Acids Res. Suppl. 2001, 1, 13-14.
[5]. Wada, T., Oka, N., Saigo. K. Nucleic Acids Res. Suppl. 2002, 2, 153-154.
[6]. Oka, N., Wada, T., Saigo. K. J. Am. Chem. Soc. 2002, 124, 4962-4963.
[7]. Oka, N., Wada, T., Saigo. K. J. Am. Chem. Soc. 2003, 125, 8307-8317.
[8]. Wada, T., Oka, N., Saigo. K. Nucleic Acids Res. Suppl. 2003, 3, 109-110.
[9]. Wada, T., Oka, N., Saigo. K. Nucleos. Nucleot. Nucl. Acids 2003, 22, 1171-1173.
[10]. Oka, N., Wada, T., Saigo. K. Nucleos. Nucleot. Nucl. Acids 2003, 22, 1411-1413.
[11]. Wada, T., Fujiwara, S., Sato, T., Oka, N., Saigo. K. Nucleic Acids Res. Symp. Ser. 2004, 48, 57-58.
[12]. Wada, T. Front. Org. Chem. 2005, 1, 41-61.
[13]. Oka, N., Maizuru, Y., Shimizu, M., Saigo, K., Wada, T. Nucleic Acids Symp. Ser. 2005, 49, 131-132.
[14]. Wada, T., Maizuru, Y., Oka, N., Saigo, K. Bioorg. Med. Chem. Lett. 2006, 16, 3111-3114
264

IL-20
3',5'-CYCLIC DIGUANYLIC ACID AND RELATED COMPOUNDS: SYNTHESIS,
CHEMICAL PROPERTIES, AND BIOLOGICAL ACTIVITIES
Yoshihiro Hayakawa
Graduate School of Information Science and CREST of JST, Nagoya University, Chikusa, Nagoya 464-8061, Japan
We synthesized cyclic bis(3'–5')diguanylic acid (c-di-GMP) and related compounds and
investigated their biological activities, such as inhibitory effects on biofilm formation of some
bacteria and on basal and growth factor-stimulated human colon cancer cell proliferation.
First, we developed the high-efficient synthesis of c-di-GMP outlined in Scheme 1, which can
provide a few grams of the target compound by one-cycle synthesis. The success was produced
mainly by the use of the following useful method and strategy. The first is the use of the
di-tert-butylsilanediyl group for protection of 3’- and 5’-hydroxy groups of guanosine, which can be
selectively removed from the 3',5'-O-di-tert-butylsilanediyl-2'-O-TBDMS guanosine intermediate
by using a mixture of HF•pyridine complex and pyridine. This strategy allowed 100%
regioselective production of the 2'-O-TBDMS guanosine intermediate. The second is employment
of our original phosphoramidite method using imidazolium perchlorate as a promoter in the
presence of molecular sieves 3A for the formation of a linear (3’–5’)diguanylic acid intermediate.
This method gave the desired product in a higher yield than the existing standard phosphoramidite
method using 1H-tetrazole as a promoter. Fundamental strategies used in this synthesis could be
applied to the synthesis of a variety of c-di-GMP artificial analogs with modified nucleobases,
sugars, and backbones. Actually, we have synthesized c-GpdGp, c-GpIp, c-GpAp, and c-GpGps
by means of strategies somewhat modified from those used in the method shown in Scheme 1.
Investigation on stability of c-di-GMP and its analogs revealed that these cyclic diribonucleotides
are stable in a human serum solution, an acid solution or a base solution. Thus, c-di-GMP was left
intact in a 100 mM or 200 mM human serum solution at 37 °C for 24 h. This nucleotide also
underwent no decomposition by treatment with a pH 3 hydrochloric acid or a pH 10 sodium
hydroxide solution at 25 °C for 1 h or at 100 °C for 10 min. The c-di-GMP analogs have similar
stability to c-di-GMP.
We next examined biological activities of c-di-GMP and its analogs. As a result, we found that
c-di-GMP appears to act as a second messenger in bacteria and shows a variety of important
bioactivities. Among them, the particularly attractive one is the regulation of biofilm formation
and infection to host cells by various bacteria; that is, inhibition of biofilm formation of S. aureus, P.
aeruginosa and E. coli; reduction of infection of S. aureus to HeLa cells; reduction of the virulence
of biofilm-forming S. aureus strains in a mouse model of mastitis infection in vivo; and activation of
immune response. According to results that we observed, it may be speculated that c-di-GMP acts
in biofilm formation and infection of a bacterium as shown in Figure 1. c-di-GMP also inhibits
basal and growth factor-stimulated human colon cancer cell proliferation. In addition,
investigations of c-dGpGp revealed that this artificial compound has different biological activities
from those of c-di-GMP. Thus, both c-di-GMP and c-dGpGp inhibit biofilm formation of S.
aureus and V. parahaemolyticus, but the strength of their inhibitory effects is not the same and
c-dGpGp has a stronger effect than c-di-GMP in either bacterium. In conclusion, our findings
described here suggest that c-di-GMP and its analogs have high potential as antibacterial and
immunotherapeutic agents.
265

IL-23
SYNTHESIS OF DINUCLEOSIDE PHOSPHATES FROM c-di-GMP TO AZTppppA
Zhaoying Zhang, Qianwei Han, Jianwei Zhao, Barbara L. Gaffney, and Roger A. Jones*
Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, Piscataway, New Jersey
08854
Bis-(3'-5')-cyclic guanosine monophosphate (c-di-GMP) is a ubiquitous bacterial signaling
molecule responsible for regulating biofilm formation, cell differentiation, and a variety of
pathogenic processes. We have recently reported a new method for its efficient chemical synthesis
involving an initial phosphoramidite coupling and a subsequent H-phosphonate cyclization. The use
of P(III) chemistry in both steps permits fast, high yield reactions. We have also synthesized and
separated diastereomers of the phosphorothioates of c-di-GMP. Further, using UV, CD, and NMR,
we have demonstrated that c-di-GMP exists as a mixture of five different but related structures in an
equilibrium that is sensitive both to its concentration and to the metal present.
Dinucleoside polyphosphates (5'-5'''-NpnN) have been proposed as signaling and regulatory
molecules for many different biological functions in most forms of life. We have reported a
one-flask, high-yield synthesis of Ap4A, Ap4G, Gp4G, and Ap5A by reaction of a nucleoside
trimetaphosphate with a nucleoside mono- or diphosphate in DMF with ZnCl2. We have also
extended this method to the preparation of versions of Ap4A with a thioate, selenoate, or boranoate
introduced into the trimetaphosphate. We have recently modified our approach so as to introduce a
thioate at both ends and have prepared a variety of modified versions of AZTp4A as potential
non-hydrolyzable inhibitors of the AZT excision reaction from HIV-1 reverse transcriptase.
266

IL-24
THE EFFECTS OF REVISIBLE PHOSPHORYLATION ON PEPTIDE AND PROTEIN
LOCAL STRUCTURE
Yan-Mei Li, Yu-Fen Zhao
Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Department of
Chemistry, Tsinghua University, Beijing 100084
The regulation of biochemical activity by protein post-translational modifications is a pervasive
cellular control mechanism. Protein phosphorylation is a key posttranslational modification
mechanism controlling the conformation and activity of many proteins. Through the use of
phosphorylation cycles and cascades, the cell is able to regulate a diverse set of processes, including
cellular movement, reproduction and metabolism. It is the simplicity, reversibility and flexibility of
phosphorylation that explains why it has been adopted as the most general control mechanism of the
cell. The use of the phosphorylation/dephosphorylation of a protein as a control mechanism has
many advantages: rapid, taking as little as a few seconds, no require new proteins to be made or
degraded and easily reversible.
With regard to its regulatory mechanism, it is of fundamental importance to study the role and
function in protein networks by phosphorylation. Increasing evidence has implicated an essential
role of phosphorylation by activating α-COOH to form amide bond in peptide synthesis, increasing
the cis content of the peptidyl-propyl amide bond, causing local structure more ordered, regulating
intrisically disorder domain, and effecting the protein distribution in cell. Phosphate acts as the
molecular switch to modulate protein networks.
Reference
[1] Chen YX, Du JT, Zhou LX, Li YM*, et al. Alternative O-GlcNAcylation/ O-Phosphorylation of Ser16 Induce
Different Conformational Disturbances to the NTesrminus of Murine Estrogen Receptor β. Chem. Biol. 2006, 13:
937-944.
[2] Du JT, Li YM*, Wei W, et al. Low Barrier Hydrogen Bond Between Phosphate and Amide Group in Phosphopeptide.
J. Am. Chem. Soc. 2005, 127: 16350-16351.
[3] Du JT, Li YM*, Ma QF, et al. Synthesis and Conformational Properties of Phosphopeptides Related to the Human
Tau Protein. Regul. Pept. 2005, 130: 48-56.
[4] Schlummer S, Vetter R, Kuder N, Chen YX, Li YM, et al. Influence of Serine O-Glycosylation or O-Phoshorylation
Close to the vJun Nuclear Localisation Sequence on Nuclear Import. ChemBioChem 2006, 7: 88-97.
[5] Chen ZZ, Tan B, Li YM*, et al. Activity Difference between α-COOH and β-COOH in N-Phosphoryl Aspartic Acids.
J. Org. Chem. 2003, 68: 4052-4058.
[6] Chen ZZ, Li YM*, Wang HY, et al. Theoretical Study on the Rearrangement of β-OH and γ-OH in ESI Mass
Spectrometry by N-phosphorylation. J. Phys. Chem. A 2004, 108: 7686-7690.
267

IL-25
ALL PHOSPHATES ARE NOT BORN CHEMICALLY EQUAL IN RNA
Jyoti Chattopadhyaya
Department of Bioorganic Chemistry, Box 581, Biomedical Center,Uppsala University, S-751 23 Uppsala, Sweden
jyoti@boc.uu.se
We here show that the electronic properties and the chemical reactivities of the internucleotidic
phosphates in the heptameric ssRNAs are dissimilar in a sequence-specific manner because of their
nonidentical microenvironments, in contrast with the corresponding isosequential ssDNAs. This has
been evidenced by monitoring the δH8G shifts upon pH-dependent ionization [pKa1] of the central
9-guaninyl(G) to the 9-guanylate ion (G−), and its electrostatic effect on each of the internucleotidic
phosphate anions, as measured from the resultant δ31P shifts [pKa2] in the isosequential heptameric
ssRNAs vis-àvis ssDNAs: [d/r(5'-Cp1Ap2Q1p3Gp4Q2p5Ap6C-3'): Q1 = Q2 = A (5a/5b) or C
(8a/8b), Q1 = A, Q2 = C(6a/6b), Q1 = C, Q2 = A (7a/7b)]. These oligos with single ionizable G in
the centre are chosen because of the fact that the pseudoaromatic character of G can be easily
modulated in a pH-dependent manner by its transformation to G− (the 2'-OH to 2-O− ionization
effect is not detectable below pH 11.6 as evident from the N1-Me-G analog), thereby
modulating/titrating the nature of the electrostatic interactions of G to G− with the phosphates,
which therefore constitute simple models to interrogate how the variable pseudoaromatic characters
of nucleobases under different sequence context [Chattopadhyaya et al J. Am.Chem. Soc, 126,
8674-8681 (2004)] can actually influence the reactivity of the internucleotide phosphates as a result
of modulation of sequence-context specific electrostatic interactions.
References
[1] J. Barman, S. Acharya, S. Chatterjee, . Engstrom and J. Chattopadhyaya, Org. Biomol. Chem, 4, 928 - 941 (2006).
[2] S. Chatterjee, W. Pathmasiri, D. Honcharenko, O. P. Varghese, M. Maiti & J. Chattopadhyaya, Org.Biomol. Chem., 4,
1675-1686 (2006)
[3] Oommen P. Varghese, Jharna Barman, Wimal Pathmasiri, Oleksandr Plashkevych, Dmytro Honcharenko, and Jyoti
Chattopadhyaya. J. Am. Chem. Soc. 128(47) pp 15173 – 15187 (2006)
268

IL-26
DESIGN, SYNTHESIS AND BIOLOGICAL ACTIVITY OF Α-AMINO-SUBSTITUTED
THIOPHOSPHATE-PHOSPHONATES AND NOVEL NAPHTHOQUINONE FUSED
PHOSPHORUS HETEROCYCLES
Zhanwei Cui Zhiwei Miao * Jianfeng Zhang Ruyu Chen
State Key Laboratory and Institute of Elemento-Organic Chemistry, Nankai University, Tianjin 300071, P.R.China
Email: miaozhiwei@syn.nankai.edu.cn
The phosphoryl group is of fundamental significance in many of the most important molecules
that control molecular replication, cell biochemistry and metabolic processes in all living species. 1-4
On the other hand, α-amino phosphonates constitute an important class of biologically active
compounds, and their synthesis has been a focus of considerable attention in synthetic organic
chemistry as well as in medicinal chemistry.
Nitrogen mustards (NMs) are useful chemotherapeutic agents in the treatment of lymphoma,
leukemia, multiple myeloma and ovarian carcinoma. 5 The antitumor activity of NMs has been
attributed to their ability to cross-link the twin strands of DNA. Phosphoramide mustard is also an
alklating agent that cross-links interstrand DNA, such as cyclophosphamide (CP),ifosfamide (IFA)
and trofosfamide. 6-9 Cyclophosphamide is a widely used anticancer alklating agent that requires
activation in vivo. It can liberate cytotoxic phosphoramide mustard and acrolein by β-elimination.
However, acrolein, a byproduct of β-elimination, can cause hemorrhagic cystitis, a side effect
observed during CP therapy. To overcome the shortcoming of CP, many different kinds of
compounds containing phosphamide mustard have been designed and synthesized. 10-12 On that basis,
we designed and synthesized the title compound to find novel anticancer prodrug.
We report here a facile synthetic method for the preparation of Diphenyl α-(O-phenyl
bis(2-chloroethyl)amidophosphorylamino)phosphonates (4). It consists of the reaction of O-phenyl
bis(2-chloroethyl)amidophosphoroamidoate (1) with a substituted benzaldehyde or ketones (2) and
triphenyl phosphite (3) in the presence of acetyl chloride as catalysis. 13 The present method affords
higher yields in the condensation reaction and high purify. (Scheme 1)
Cl
Cl
N
O
P
O
1
NH 2 +
R 1
O
R 2
+ (PhO) 3P
2 3
Scheme 1
269
O
Cl
r.t., 6-8h
R1 H
N C
4 R 1 R 2 Yield (%) 4 R 1 R 2 Yield (%)
4a H C 6H 5 92 4f H 4-ClC 6H 4 89
4b H 4-MeC6H4 90 4g H 4-BrC6H4 84
4c H 4-MeOC6H4 90 4h (CH2) 4 75
4d H 4-O2NC6H4 86 4i (CH2) 5 73
4e H 3,4-OCH2OC6H3 89
Cl
Cl
N
O
P
O
4
R 2
O
P
OC 6H 5
OC 6H 5

Reference
1. Zhou, J.; Chen, R. Y. Phosphorus, Sulfur, Silicon 1996, 118, 247.
2. Bergman, J.; Van der Plas, H. C.; Simonyi, M. Heterocycles in Bioorganic Chemistry; RSC: Cambridge, 1991.
3. Meier, C. Angew. Chem., Int. Ed. Engl., 1996, 35, 70.
4. Yuan, C.; Qi, Y. Synthesis 1986, 821.
5. Balcome, S.; Park, S.; Danae R.; Dorr, R.; Hafner, L.; Phillips, L.; Tretyakova, N. Chem. Res. Toxicol. 2004, 17,
950-962.
6. Sladek, N. E. Pharmacol. Ther. 1988, 37, 301-305.
7. Friedman, O. M.; Myles, A.; Colvin, M. Adv. Cancer Chemother. 1979, 1, 143-204.
8. Ludeman, S. M. Curr. Pharm. Des. 1999, 5, 627-643.
9. Colvin, O. M. Curr. Pharm. Des. 1999, 5, 555-560.
10. Borch, R. F.; Liu, J. W.; Schmidt, J. P.; Marakovits, J. T.; Joswig, C.; Gipp, J. J.; Mulcahy, R. T. J. Med. Chem.
2000, 43, 2258-2265.
11. Hu, L. Q.; Yu, C. Z.; Jiang, Y. Y.; Han, J. Y.; Li, Z. R.; Browne, P.; Race, P. R.; Knox, R, J.; Searle, P. F.; Hyde,
E. I. J. Med. Chem. 2003, 46, 4818-4821.
12. Jain, M.; Kwon, C. H. J. Med. Chem. 2003, 46, 5428-5436.
13. Yuan, C.; Qi, Y. Synthesis .1988, 472.
270

IL-27
RECENT ADVANCES IN CARBAMOYLPHOSPHONATE BASED MATRIX
METALLOPROTEINASE (MMP) INHIBITORS. A CLASS OF NON-TOXIC IN-VIVO
ACTIVE DRUG CANDIDATES
Eli Breuer
Department of Medicinal Chemistry, School of Pharmacy, The Hebrew University of Jerusalem,
Jerusalem, 91120 Israel
Matrix metalloproteinases (MMPs) are a family of about 26 zinc-dependent endopeptidases,
which collectively have the capacity to degrade all the major components of the extracellular
matrix. [1] Although the MMPs play a crucial role in physiological tissue remodeling, growth and
repair, their over-expression has been linked with severe chronic pathological conditions, including
cancer, arthritis, several cardiovascular disorders and others. The efficient inhibit-ion of MMPs is,
therefore, an important scientific and therapeutic target, which has attracted considerable attention
within academia and industry for the last two decades. Yet, in spite of intensive worldwide research,
which has yielded a multitude of highly in vitro potent inhibitors, no clinically useful inhibitor has
been achieved. The main reasons for this failure probably have to do with unacceptable side effects
resulting presumably from lack of selectivity of two kinds: 1) lack of differentiation between the
various MMP subtypes; and 2) lack of selectivity toward various metal cations present in the
organism. [2]
As the Zn 2+ ion at the active sites of these enzymes is crucial for enzymatic activity, all attempts
to develop inhibitors have been based on so-called zinc binding groups (ZBG). It has also been
pointed out that the use of highly potent ZBGs might lead to a limitation in finding specific
metalloproteinase inhibitors. The presence of a similar metal chelation topology in independently
identified and structurally unrelated lead compounds indicates that Zn 2+ binding follows a rather
universal recognition motif, which dominates the binding characteristics. Consequently, many if not
most potent active site directed Zn 2+ protease inhibitors exploit such a universal binding motif, and
are likely to exhibit a low specificity profile, at least prior to optimization, which is usually
attempted through substituent group modification. Accordingly, for the design of more selective
MMPIs, weaker ZBGs should be preferred.
We have recently introduced the carbamoylphosphonic group as a novel ZBG. [3] We have
synthesized carbamoylphosphonates of various structures, [4] and evaluated them in numerous in
vitro and in vivo biological models, related to cancer metastases, angiogenesis, cardiovascular
disease, wound healing and others. Thus, we have discovered novel, in vivo potent and nontoxic
inhibitors.
This lecture will describe the recent advances in our work on carbamoylphosphonate based MMP
inhibitors, including the mode of MMP inhibition, structure-activity relationships, in vivo results
obtained in disease models, and the unique pharmacokinetic characteristics of this class of polar
compounds.
Reference
[1] J. W. Skiles, N. C. Gonnella, A. Y. Jeng. Current Med. Chem. 2004, 11, 2911.
[2) E. Breuer, J. Frant and R. Reich, Expert Opin. Ther. Patents, 2005, 15, 253.
[3] E. Farkas, Y. Katz, S. Bhusare, R. Reich, G.-V. Röschenthaler, M. Königsmann, and E. Breuer, J. Biol. Inorg. Chem.
2004, 9, 307.
[4) E. Breuer, C. J. Salomon, Y. Katz, W. Chen, S. Lu, G.-V. Röschenthaler, R. Hadar, and R. Reich, J. Med. Chem.
2004, 47, 2826.
271

IL-48
NOVEL FUNCTIONALITY IN ORGANOPHOSPHORUS CHEMISTRY
Koop Lammertsma
Department of Chemistry, Faculty of Sciences,Vrije University, Amsterdam, the Netherlands
Phosphinidenes R-P are remarkably reactive. For long they eluded spectroscopic detection other
than by EPR. Only recently were we able to obtain IR and UV spectra of the mesityl derivative
under matrix isolation conditions. Those complexed to transition metal groups are spectroscopically
equally elusive when they are of the Fischer-type, but their very rich chemistry sharply contrasts
that of triplet Mes-P. In this presentation we elaborate on synthetic routes by which the electrophilic
and nucleophilic R-P=MLn can be generated and used. This reactivity of these species will be
addressed. Analogies with hydrocarbon chemistry will also be highlighted in the rearrangement of
selected products.
Me
Me
Me
P
Ru
Highly strained, yet stable P-containing ring structures, such as bicyclobutanes and
(poly)spiranes, can be synthesized with the aid of electrophilic R-P=MLn. Selected novel examples
will be presented.
N
i-Pr
P
Fe(CO) 4
O
P
N'
N
N
N N
Ph
Rh
N
Cl Cl Cl
272
P
Mes*
N Ph
N
R 2
N C
Cp*
Ir
P
C
P
R
R 3
ML n
N R 1

IL-64
STUDYING THE PHOSPHORYLATION OF FLAVONOIDS
E. E. Nifantyev 1 , M. P. Koroteev 1 , G. Z. Kaziev 1 , T. Wang 1 , and L. H. Cao* ,2
1 Department of Chemistry, Moscow State Pedagogical University, 119021, Moscow Russia
2 College of Chemistry and Chemical Engineering, Xinjiang University, 830046, Urumqi China P.R.
Phosphorylation of dihydroquercetin (1) and other flavonoids with tervalent phosphorus reagents
was studied. It was found that flavonoid 1 can be directionally phosphorylated with phosphorous
acid amides under mild conditions:
The resulting product 2 was easily reacted with sulfur to form thiophosphate 3, which has
antitumoral activity. Phosphite 5 was obtained when tetramethyldihydroquercetin (4) was treated
with P(NEt2)3:
Under slight heating, 5 forms phostone 6, whose structure was supported by X-ray diffraction
analysis.
273

O-56
CATIONIC LIPIDS BASED ON PHOSPHONATE & PHOSPHORAMIDATE CHEMISTRY:
SYNTHESIS AND APPLICATION TO GENE THERAPY
Paul-Alain Jaffrès a , Mathieu Mével a , Jean-Jacques Yaouanc a , Jean-Claude Clément a ,
Dominique Cartier a , Laure Burel, Philippe Giamarchi, Tristan Montier b , Pascal Delépine b ,
Pierre Lehn b , Claude Férec b , Chantal Pichon c , Patrick Midoux c .
a- CEMCA, UMR CNRS 6521, Faculté des Sciences et Techniques, Université de Bretagne Occidentale, 6 avenue Le
Gorgeu, 29238 Brest, (France) ; b-Unité INSERM 613, Institut de Synergie des Sciences et de la Santé, Université de
Bretagne Occidentale, avenue Foch, 29609 Brest cedex 2 (France); c-Centre de Biophysique Moléculaire, CNRS UPR
4301, rue Charles Sadron, 45071 Orléans (France)
Vectorisation of DNA into cells, which is required for gene therapy or cancer therapy, can be
achieved according to two distinct strategies. One is based on the use of viral vectors while the
second concerns the use of synthetic vectors. Synthetic vectors are very promising due to both their
ability to carry large plasmid and the absence of immunogenic side effect. The chemical structure of
the synthetic vectors can be classified into two categories: cationic polymers (e.g.PEI) and cationic
lipids (schematized below). Despite the recent progress proving that cationic lipids or cationic
polymers can be efficient for gene delivery, further improvement in term of efficiency of
transfection should be done for clinical use. In our group, cationic lipids, possessing a molecular
structure inspired from phospholipids present into membranes, have been synthesized over the last
10 years. The chemical structures of these vectors are characterized by the presence of a
phosphonate (A) or phosphoramidate (B) functional group on which the lipid chains are linked.
Several chemical variations on the lipid chain, the linker or the cationic head group have been
investigated. These chemical modifications and optimizations lead to synthetic vectors [1] efficient as
gene carrier for in vitro [2] and in vivo [3] essays.
Reference
[1] J.C. Clément, P. Delépine, H des Abbayes, C. Férec, K. Le Ny, T. Montier, J.J. Yaouanc, French patent N°0214044
(2002). Extension Int. (PCT) (2003)
[2] (a) Guenin, E.; Hervé, A.C.; Floch, V.; Loisel, S.; Yaouanc, J.J.; Clément, J.C.; Férec, C; des Abbayes, H.Angew.
Chem. Int. Ed. Engl. 2000, 39, 629-631. (b) T. Montier, P. Delépine, K. Le Ny, Y. Fichou, M. Le Bris, E.Hardy, E.
Picquet, J.C. Clément, J.J. Yaouanc, C. Férec, Biochimica & Biophysica Acta 2004, 1665, 118-133
[3] (a) Gable-Guillaume, Floch, V.; et. al., Hum. Gene Ther. 1998, 9, 2309-2319. (b) P. Delépine, C.Guillaume, et. al.,
Gene Medecine 2003, 5, 600-8 ; (c) E. Picquet, K. Le Ny, et. al., Bioconjugate Chem., 2005, 16, 1051-53
274

O-57
ENANTIOMERIC SEPARATION OF A NOVEL Α-ANMINOPHOSPHONATES
CONTAINING BENZOTHIAZOL MOIETY BY LIQUID CHROMATOGRAPHY USING
AMYLOSE STATIONARY PHASE
Ping Lu, Baoan Song, Deyu Hu, Song Yang, Linhong Jin, Wei Xue, Yuping Zhang
Center for Research and Development of Fine Chemicals, Key Laboratory of Green Pesticide and Agriculture
Bioengineering, Ministry of Education, Guizhou University, Guiyang 550025, P.R. China.
α-Aminophosphonate derivatives have attracted much attention in medicinal and pesticide
chemistry due to their bioactivities. Some recemates of N-(substituent– benzothiazole-2-yl) -1-(substient-fluorophenyl)-O,
O-dialkyl-α-aminophosphonate were found to possess good antiviral activity. To the best of our
knowledge, the enantioseparation methods of recemates and the bioactivity results of enantiomers
of this series of α-aminophosphonates are not available in the literature. The present report
describes a chiral HPLC method for the entiomeric separation of these α-aminophosphonate
derivatives using both coated and immobilized amylase-based CSP (Chiralpak IA and Chiralpak
AD-H). The various chromatographic parameters such as retention factor (k’), separation factor (α),
and resolution (Rs) of the solutes are investigated. Reasonably good baseline separation for these
compounds was achieved using Chiralpak IA column under normal phase with n-hexane/ethanol
(95:5, v/v). The validated method yields good results for precision, linearity and accuracy. In order
to study the chiroptical properties and bioactivity of single stereoisomer, mg-scale separations were
performed on semipreparative size Chiralpak IA column in combination with ethanol-based eluents.
Every enantiomer was isolated with purity of > 98.0 e.e. and >96.0% recovery. The proposed
method was found to be suitable and accurate for rapid determination of enantiomeric purity of this
series of α-aminophosphonate derivatives.
(1) (2)
(3)
Fig. Chromatograms of N-(4-methyl-benzothiazole-2-yl)-1-(2-fluorophenyl)-O,O-diethyl- α-aminophosphonate
racemate (1), R-isomer (2) and S-isomer (3) isolated at 270nm on the Chiralpak IA using n-hexane and ethanol (95:5,
v/v), 1.0mL/min.
275

O-58
BEAD-BASED APPROACHES TO DEVELOP THIOAPTAMERS FOR
DIAGNOSTICS AND THERAPEUTICS
Xianbin Yang 1 , Duane Beasley 1 , Bruce A. Luxon 2 , Johnnie Engelhardt 1 , Mark Shumbera 1 , David G. Gorenstein 2 .
1 AM Biotechnologies LLC, 6023 Ave. S. #228, Galveston, Texas 77551, USA; 2 Sealy Center for Structural Biology,
Department of Biochemistry and Molecular Biology, The University of Texas Medical Branch at Galveston, Texas
77555, USA.
Aptamers [1,2] with normal phosphate ester backbones obtained from the in vitro selection process
were discovered in the early 1990s and have proven very useful as therapeutic and diagnostic agents.
In December 2004, an aptamer for vascular endothelial growth factor, Macugen, made headlines as
the first of its class to be approved by the US Food and Drug Administration. However, the aptamer
selection method is limited to substrates and templates accepted by the polymerases required for
reamplification by PCR of the selected libraries. In addition, selection is a time consuming process
which involves multiple rounds of alternating selection and amplification steps in order to
successively enrich aptamer sequences that show the desired properties. Thioaptamers [3] , which are
thiophosphate ester backbone modified nucleic acid aptamers, offer advantages over normal
aptamers due to their enhanced affinity and higher stability stemming from the properties of the
sulfur backbone modifications. Over the past several years, we have demonstrated proof-of
principle that a novel bead-based approach [4] can be employed to develop aptamers, thiopaptamer
and other modified aptamers as well. In this presentation, we will outline our integrated novel
bead-based selection procedures including the automation of the split-pool synthesis of a one-bead
one-thioaptamer library, high-throughput flow cytometric sorting and a PCR-based sequencing.
Additionally, we will also discuss several promising thioaptamers which have been shown in
preliminary animal therapeutic dosing to increase survival in animal models of infection with West
Nile virus [5] . Moreover, we will present a thioaptamer proteomics chip. (Note: Drs Gorenstein and
Luxon have a financial interest in AM Biotechnologies).
Reference
[1] C. Tuerk, and L. Gold, Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage
T4 DNA polymerase. Science 249 (1990) 505-10.
[2] A.D. Ellington, and J.W. Szostak, In vitro selection of RNA molecules that bind specific ligands. Nature 346 (1990)
818-22.
[3] X. Yang, and D.G. Gorenstein, Progress in thioaptamer development. Curr Drug Targets 5 (2004) 705-15.
[4] X. Yang, S.E. Bassett, X. Li, B.A. Luxon, N.K. Herzog, R.E. Shope, J. Aronson, T.W. Prow, J.F. Leary, R. Kirby,
A.D. Ellington, and D.G. Gorenstein, Construction and selection of bead-bound combinatorial oligonucleoside
phosphorothioate and phosphorodithioate aptamer libraries designed for rapid PCR-based sequencing. Nucleic Acids
Res 30 (2002) e132.
[5] X. Yang, H. Wang, D. Beasley, D. Volk, X. Zhao, B. Luxon, L. Lomas, N. Herzog, J. Aronson, A. Barrett, J. Leary,
and D. Gorenstein, Selection of Thioaptamers for Diagnostics and Therapeutics. Annals of the New York Academy of
Sciences. 1082 (2006) 116-119.
276

O-59
DESIGN AND CONSTRUCTION OF DIAGNOSTIC CHIPS FOR CANCERS
Anna Czernicka and Paweł Kafarski
Department of Bioorganic Chemistry Faculty of Chemistry,Wrocław University of Technology,Wybrzeże.
Wyspiańskiego 27, 50-370 WROCŁAW; Poland
In the past few years, miniaturized and parallel assay systems, especially microarraybased
analyses have shown its great potential in basic research, drug discovery and diagnostics. The
development of these tools was possible due to progress in the area referred as chip technology.
The aim of the presented studies it is to construct prototype organophosphorous diagnostic chips
composed of arrays of peptide derivatives covalently bound to the glass and/or filter paper surface.
These peptides might serve as fluorogenic substrates or inhibitors of marker proteins being
overproduced during cancer development. Thus, by manipulating the chemical structure of the
aminophosphonate and the amino acid composition of the peptide it is possible to design and
synthesize libraries reacting differently with healthy and tumorous cell extracts. The first step of
implementation this project is synthesis of diaryl or dialkyl Z-aminophosphonates, witch could be
applied for qualitative and quantitative determination of proteolytic activity of certain tumor tissues
in comparison with healthy ones. The composition of these libraries was strongly dependent on
choice and properties of fluorogenic groups used as features of presumable inhibitors and substrates
of proteases. This is because immobilization of these probes is far easier than production of
sensitive fluorescence change. The fluorogenic groups were synthesized by application of several
methods. Among them unusual application of Suzuki coupling in organophosphorus chemistry was
proposed.
Also the preliminary evaluation of efficiency of these compounds using thyroid cancer cell
extracts will be shown
277

O-62
FACTORS THAT MAY PREDICT CLINICAL POTENCIES OF
NITROGEN-CONTAINING BISPHOSPHONATES; NOVEL METHODS DISSOCIATE
ENZYME- AND HYDROXYAPATITE-BINDING AFFINITIES
Z.Xia 1 ,J.Dunford 1 ,M.A.Lawson 1 ,J.T.Triffitt 1 ,B.L.Barnett 2 ,C.Roze 3 ,B.Kashemirov 3 ,C.E.McKenna 3 , F.H.Ebetino 2 and
R.G.G. Russell
1 The Oxford University Institute of Musculoskeletal Sciences, The Botnar Research Centre, Nuffield Orthopaedic
Centre, Oxford,OX3 7LD, UK; 2 New Drug Development, Procter and Gamble Pharm, Cincinnati OH, USA, 3 Chemistry
Department, University of Southern California, Los Angeles, CA
Bisphosphonates (BPs) have pharmacological potencies that are dependent on both the binding
affinities for bone mineral and inhibitory effects on the cellular activities of the major
bone-resorbing cells, the osteoclasts. The latter cellular effects are mediated in the case of
nitrogen-BPs by selective targeting of the enzyme Farnesyl Diphosphate Synthase (FDPS). The
extent to which each factor determines the functional properties of individual BPs can be better
defined by assays for FDPS activity and mineral binding. This study has employed a recently
developed mineral binding assay that is highly reproducible and based on ceramic hydroxyapatite
(HAP) column chromatography. Inhibitory potencies of individual BPs on FDPS were measured by
kinetic investigations. These studies indicate that the nitrogen containing bisphosphonates (N-BPs)
inhibit the enzyme by initially competing with the substrate geranyl pyrophosphate and
subsequently bind in a slow tight manner. From the use of a variety of N-BPs, it is shown that that
the rank order for inhibitory potencies on FDPS is independent of the respective mineral binding
affinities to HAP (Table 1). Major determinants of mineral binding are confirmed to be the P-C-P
group, an OH on the carbon, and the structure and orientation of a second nitrogen containing
substituent on the carbon. For the inhibition of FDPS the PCP groupis also essential (via Mg 2+
binding), together with specific orientation of the N in the R2 group relative to the enzyme binding
pocket. These results are aided by molecular modelling to illustrate how different 3-D
configurations of the nitrogen containing substituents in the different BPs, in relation to the overall
BP structures, can account for the observed FDPS inhibition and HAP-binding characteristics.
In conclusion, the chemical structures that determine independently the FDPS inhibition and
mineral binding activities of N-BPs are distinctive and contribute separately to the overall observed
clinical potencies of N-BPs in vivo.
N-BPs Retention time (min, mean±SE) Ki app (nM)
Risedronate-R1 Fluorine 5.93±0.11 11.5
Risedronate-R1Bromine 5.83±0.17 220
Risedronate-R1 Chlorine 5.93±0.07 47.7
NE97220 ( a 3-Me 2-pyridyl aminomethane BP) 6.53±0.15 6.3
NE58022 (Phenyl analogue of Ris) 7.77±0.15 293
Homorisedronate (NE58051) 9.67±0.09 218
Risedronate 9.97±0.09 2.0
Zoledronate 12.53±0.06 0.4
278

O-63
NOVEL ORGANOPHOSPHORUS INHIBITORS OF GLUTAMINE SYNTHETASE
Łukasz Berlicki 1 , Agnieszka Grabowiecka 1 , Giuseppe Forlani 2 and Paweł Kafarski 1
1 Department of Bioorganic Chemistry Wrocław University of Technology,Wybrzeże Wyspiańskiego 27, 50-370
Wrocław; POLAND 2 Department of Biology, University of Ferrara,Via L. Borsari 46, 44100 Ferrara, ITALY
Glutamine is one of the most important intermediates in nitrogen metabolism in cell.Glutamine
amide nitrogen atom is utilized as a donor for biosynthesis of several crucial metabolites — amino
acids, nucleic acids and aminosugars [1] . Thus, the enzyme which catalyses the synthesis of
glutamine from glutamate and ammonium ion — glutamine synthetase (E.C. 6.3.1.2, GS) is of high
importance for nitrogen metabolism. Inhibitors of glutamine synthetase exhibit interesting
applications both in medicine and agriculture. It was proven that they could be efficient
antituberculosis drugs by inhibiting the growth of the pathogen — Mycobacterium tuberculosis [2] .
Preliminary data suggest also that inhibitors of GS could be useful in cancer therapy [3] . On the other
side, one of the most potent inhibitors of GS — phosphinothricin (1) is commercially available total
herbicide. The inhibition of GS in plant causes accumulation of toxic ammonia [4] . Thus discovery
of novel, potent and selective GS inhibitors is of high interest.
Rational discovery of novel inhibitors should be based on the knowledge on the structure of
active site, mechanism of the reaction and interactions between substrates, products and inhibitors
with protein. Thus, we have docked known inhibitors of GS to its active site and analyzed important
structural and electronic features of these compounds [5] .Then, using LUDI program, several new
inhibitors were designed. After evaluation of their synthetic accessibility, we have chosen five
structures and synthesized them in enantiomerically pure form. Kinetic measurements showed that
obtained inhibitors rank between most active GS inhibitors (Ki = 0.59 μM was found for compound
(2)) [6] . Analysis of these data allowed to design the next generation of GS inhibitors with additional
hydroxyl group in gamma position (structure (3) is the representative example). Selected
compounds were synthesized and evaluated for their biological activity.
References
[1]. Purich, D.L. Adv. Enzymol. 1998, 72, 9.
[2]. Harth, G.; Horwitz, M.A. Infect. Immun. 2003, 71, 456.
[3]. Rotoli, B.M.; Uggeri, J.; Dall'Asta, V.; Visigalli, R.; Barilli, A.; Gatti, R.; Orlandini, G.; Gazzola, G.C.; Bussolati, O.
Cell Physiol. Biochem. 2005, 15, 281.
[4]. Wild, A.; Sauer, H.; Rühle, W. Z. Naturforsch, 1987, 42, 263.
[5]. Berlicki, Ł.; Kafarski, P. Bioorg. Med. Chem. 2006, 14, 4578.
[6]. Berlicki, Ł.; Obojska, A.; Forlani, G.; Kafarski, P. J. Med. Chem. 2005, 48, 6340.
[7]. Forlani, G.; Obojska, A.; Berlicki, Ł.; Kafarski, P. J. Agric. Food Chem. 2006, 54, 796.
279

O-67
INVESTIGATIONS INTO THE OXIDATIVE STABILITY OF HYDROXYMETHYL- AND
BIS(HYDROXYMETHYL)PHOSPHINES
D. V. Griffiths and H. J. Groombridge.
School of Biological and Chemical Sciences, Queen Mary, University of London, London, E1 4NS, UK.
It has been reported that chelate systems containing the bis(hydroxymethyl)phosphine unit,
(HOCH2)2PR, display an unusually high level of oxidative stability. [1] As part of an ongoing
programme to develop novel hydrophilic ligands for medical imaging, we were interested to
ascertain whether this oxidative stability was an inherent feature of the
bis(hydroxymethyl)phosphine groups or simply a function of the conformations adopted by these
specific chelate systems. We also wished to establish whether the hydroxymethylphosphine unit,
HOCH2PRR’, would confer a similar level of oxidative stability to that reported for the
bis(hydroxymethyl) system.
We have investigated the preparation of benzylethyl(hydroxymethyl)phosphine 1 and
benzylbis(hydroxymethyl)phosphine 2, as model systems, in order to assess their oxidative stability
compared with the trialkyl phosphine, benzyldiethylphosphine 3. These studies indicated that
neither of the hydroxymethylphosphine centres in 1 and 2 displayed a significantly enhanced level
of oxidative stability. The unusually high stability of hydroxymethylphosphine chelates previously
reported would therefore appear to arise from the overall structure of these systems rather than the
intrinsic stability of the hydroxymethylphosphine centres. In addition, the synthesis of the
hydroxymethylphosphines was complicated by the formation of hemiacetal derivatives e.g. 4 and 5
as well as other by-products e.g. 6 and 7. This is likely to limit the usefulness of the
hydroxymethylphosphines in commercial radiopharmaceutical applications.
P
O OH P
4
OH
5
P +
OH
OH
OH
6 7
280
O
P
O
OH
O OH
Reference
[1].K. V. Katti, K. Raghuraman, N. Pillarsetty, W. A. Volkert, S. S. Jurisson and T. J. Hoffman, Technetium, Rhenium
and Other Metals in Chemistry and Nuclear Medicine 6, 69-72, Eds., M. Nicolini, G. Bandoli and U. Mazzi, SGE
Editorali, Padova, Italy, 2002.
OH
OH

O-69
ORGANOPHOSPHONATE INHIBITORS OF CATHEPSINS
Paweł Kafarski
Departament of Bioorganic Chemistry, Faculty of Chemistry, Wrocław University of Technology, Wybrzeże
Wyspiańskiego 27, 50-370 Wrocław, Poland
Lysosomal cysteine proteases, generally known as the cathepsins, play an important role in many
physiological processes such as protein degradation, antigen presentation, bone resorption and
hormone processing. They have also been implicated in many pathological processes including
tumor invasion and metastasis.
For several years we have been engaged in the design and synthesis of phosphono- and
phosphinopeptides as inhibitors of chosen proteases, mostly of metalloproteases. These compounds
are considered to be the closest analogues of the high energy tetrahedral transition-state of the
amide bond hydrolysis. However, similar approach directed towards cysteine proteases failed and
organophosphonates are widely believed as being weak inhibitors of these enzymes.
Here we describe two approaches leading to reasonable inhibitors of cathepsin C and related
cathepsins. The first one relays on construction of tripeptide mimetics 1, which appeared to be
moderate inhibitors of cathepsin C. Although designed as transition state analogues, they
surprisingly exhibited non-competitive mode of binding to the enzyme. Differences in kinetics of
C-terminal acids and esters have been additionally observed
H 2N
O
H
N
O OH
P
R
1
COOR'
281
H 2N
O
H
N
R
2
OH
PO 3R' 2
The second approach based on synthesis of dipeptide mimetics 2 containing C-terminal
phosphonate analogues of bestatin. These compounds appeared to be a new class of very promising
inhibitors of cathepsin C. They appeared to be reversible, competitive and slow binding inhibitors,
with the equilibrium in the inhibitor binding reached within several minutes after addition of
cathepsin C to the mixture of inhibitor and substrate. To our best knowledge the binding affinities of
the two strongest inhibitors towards the enzyme rank amongst the highest, if considering all
low-molecular compounds. Their analogues also appeared to rank amongst the best inhibitors of
other cysteine proteases, namely of papain and cathepsins B and K. Binding mode of these
compounds was studied by means of molecular modelling of the inhibitor-protein interactions by
application of the method implemented in the Ludi program.

O-70
SYNTHESIS AND DENTAL ASPECTS OF
1,3-BIS(METHACRYLAMIDO)PROPANE-2-YL DIHYDROXYPHOSPHATE
F. Zeuner, N. Moszner and J. Angermann
voclar Vivadent AG, Research & Development FL-9494 Schaan/Liechtenstein
Phosphoric acid monoesters 1 and 2 of hydroxyalkyl methacrylates are favourable as components
for dentin adhesives. Due to their acidity they are able to remove the smear layer on dentin and
achieve a strong bond between the restorative material and the tooth substance. However, a
disadvantage of these polymerizable phosphoric acids is their low hydrolytic stability. This problem
should be overcome with monomer 3 containing more hydrolytically stable bonds between the
polymerizable methacrylic group and the strong acidic phosphorus group:
Moreover, in comparison to 1 and 2, compound 3 should have improved polymerizability. The
presentation describes the synthesis, characterization and dental aspects like radical polymerization,
hydrolytic stability, acidity and adhesive properties of the new monomer 3.
282

O-71
NEW EFFICIENT SYNTHESIS OF 2-SUBSTITUTED
BENZOTHIENO[3,2-d]PYRIMIDIN-4(3H)-ONES VIA AN IMINOPHOSPHORANE
Sheng-Zhen Xu, Yang-Gen Hu, Ming-Wu Ding*
Key Laboratory of Pesticide & Chemical Biology of Ministry of Education, Central China Normal University, Wuhan,
430079, P. R. China
Thienopyrimidine are of great importance because of their significant antifungal and antibacterial
activities, as well as their good anticonvulsant and angiotensin or H1 receptor antagonistic
activities. 1 Here we wish to report a new efficient synthesis of benzothieno[3,2-d]
pyrimidin-4(3H)-ones.
Iminophosphorane 1 reacted with aromatic isocyanates to give carbodiimides 2, 2 which were
allowed to react with secondary amines, phenols or ROH in the presence of catalytic amount of
potassium carbonate or RO - Na + to give 2-substituted benzothieno[3,2-d] pyrimidin-4(3H)-ones 4 in
good yields.
S
1
COOEt
N=PPh 3
ArNCO
S
2
COOEt
N=C=NAr
HY
The reaction of carbodiimides 2 with primary amine RNH2 (R ≠ H, Me) in the presence of
sodium ethoxide produced selectivly one of the regioisomer 6 via base catalytic cyclization
mechanism. However, another regioisomers 7 were obtained as RNH2 (R=H, Me) were used in the
absence of sodium ethoxide, via a direct cyclization mechanism.
S
2
S
COOEt
N=C=NAr
N
O
N
7
(R = H, Me)
R
NHAr
RNH2
283
S
S
5
S
N
3
6
COOEt
NHAr
Y
EtONa
N
COOEt
N
(R = Et, Pr, Bu, etc)
References:
1. Chambhare, R. V.; Khadse, B. G.; Bobde, A. S.; Bahekar, R. H. Eur. J. Med. Chem. 2003, 38, 89.
2. Braese, S.; Gil, C.; Knepper, K.; Zimmermann, V. Angew. Chem. Int. Ed. 2005, 44, 5188.
N
NHAr
NHR
O
Ar
NHR
S
4
N
O
N
Y
Ar

P-3
CALIXARENE METHYLENEBISPHOSPHONIC ACIDS: ALKALINE PHOSPHATASE
INHIBITION AND DOCKING STUDIES
A. Vovk a , V. Kalchenko b , O. Muzychka a , V. Tanchuk a , I. Muravyova a ,
A. Shivanyuk b , S. Cherenok b and V. Kukhar a
a Institute of Bioorganic Chemistry and Petrochemistry, NAS of Ukraine,02660, Kyiv-94, Ukraine.
b Institute of Organic Chemistry, NAS of Ukraine,02094, Kyiv-94, Ukraine
Calix[4]arenes bearing one or two methylenebisphosphonic acid fragments were characterized as
efficient calf intestine alkaline phosphatase inhibitors [1]. In this study, kinetics of interaction of
these compounds with alkaline phosphatase isoenzymes are analysed.
Calix[4]arene bis-methylenebisphosphonic acid 1 displayed stronger inhibition of alkaline
phosphatase from bovine intestine mucosa than calix[4]arene methylenebisphosphonic acid 2. At
the same time these macrocyclic compounds showed almost identical affinities to bovine kidney
isoenzyme. For elucidation of the molecular mechanism of inhibition the tested compounds 1 and 2
were docked computationally to the active site of E. Coli alkaline phosphatase. On the basis of
results obtained the possible role of functionally important amino acid residues in formation of
enzyme-inhibitor complex at the active centre of alkaline phosphatase is discussed.
References
[1] A.I. Vovk, V.I. Kalchenko, S.A. Cherenok, V.P. Kukhar, O.V. Muzychka,M.O. Lozynsky. Org. Biomol. Chem.
2004, 2, 3162-316
284

P-5
α-(N-BENZYLAMINO)BENZYLPHOSPHONIC ACIDS: STEREOSELECTIVITY OF
BINDING TO PROSTATIC ACID PHOSPHATASE
O.I. Kolodiazhnyi, A.I.Vovk, I.M. Mischenko, S.V. Tanchuk, G.A. Kachkovskyi, S.Yu. Sheiko, V.P. Kukhar
Institute of Bioorganic Chemistry and Petrochemistry, National Academy of Sciences of Ukraine, Murmanskaia 1, Kyiv,
UKRAINE E-mail: oikol123@rambler.ru
On the previous ICPC we have reported the asymmetric synthesis of (R)- and
(S)-α-(N-benzylamino)-benzylphosphonic acids and (1R2S)-,(1S2R)-(N-phenylethyl)amino]
arylmethylphosphonic acids (1a,b and 2a,b) of high enantiomeric purity.
HO
HO
O
P Ar -
+
H NH2CH(Me)Ph CI
(RS)-1a, (RS)-2a
285
HO
HO
Ar = Ph (1a,b); Ar =4-C 6 H 4 OMe (2a,b)
O
P Ar
CI
-
+
H NH CH(Me)Ph
2
(SR)-1b, (SR)-2b
Continuing the studies of properties of these compounds, we have tested the activities of
enantiomerically pure α-(N-benzylamino)benzylphosphonic acids against human prostatic acid
phosphatase[1-3] -α-(N-Benzylamino) benzylphosphonic acids have been shown to be a potent
inhibitors exhibiting high specificity toward acid phosphatase from human prostate [1] . As expected,
(R)-α-(N-benzylaminobenzylphosphonic acid demonstrated higher affinities for enzyme than
(S)-enantiomer. However, (1R2S)-phenyl- [1-(phenylethyl)amino]methyl-phosphonic acid 1a was
found to be 40 fold weaker inhibitor than its (1S2R)-analogue 1b. Experimentally tested phosphonic
acids 1a,b and 2a,b have been docked computationally to the active centre of this enzyme.
Implications of theoretical results to the mechanisms of stereospecificity of inhibition of prostatic
acid phosphatase by α-benzylaminobenzylphosphonic acids are discussed.
References
[1] S.A. Beers, C.F. Schwender, D.A. Loughney, E. Malloy, K. Demarest, J. Jordan. Bioorg. Med. Chem. 1996, 4,
1693-1701.
[2] O.I. Kolodiazhnyi, S. Sheiko, I. Guliaiko, E. Grishkun Abstracts of XV International conference on phosphorus
chemistry. Sendai, Japan. 2001. P. 211; Phosphorus, Sulfur and Silicon and related elements (USA) 2002, 177,
2269-2270.
[3] G.A. Kachkovskii, N.V. Andrushko, S.Yu. Sheiko, and O.I. Kolodiazhnyi. Russ. J. Gen. Chem. 2005, 11, 1735-1743.

P-11
GERANYL AND FARNESYL BISPHOSPHONATES INHIBIT PROTEIN
GERANYLGERANYLATION THROUGH ggpp DEPLETION
Andrew J. Wiemer, Huaxiang Tong, David F. Wiemer, Raymond J. Hohl.
University of Iowa. E-mail: raymond-hohl@uiowa.edu
The proliferation of many human cancers is regulated in part by the Ras superfamily of small
GTPases. The function of these proteins is dependent upon their post-translational linkage to
either farnesyl or geranylgeranyl groups that are derived from their respective isoprenoid
pyrophosphates. Nitrogenous bisphosphonates, which are used clinically to treat osteoporosis,
also deplete cells of isoprenoid pyrophosphates leading to diminished protein isoprenylation
although the relationship of the clinical activity to this effect is not completely clear. The clinical
nitrogen-containing bisphosphonates diminish both farnesylation and geranylgeranylation. Our
lab has designed and synthesized a series of novel isoprenoid bisphosphonates (e.g. the digeranyl
bisphosphonate 1) that impacts protein geranylgeranylation but not farnesylation (Bioorg Med
Chem, 2006, 14:4130-6).
This current structure-function study outlines the biological activity of various geranyl- and
farnesyl-containing bisphosphonates and their olefin isomers. As with digeranyl bisphosphonate,
cells treated with these analogs are depleted of intracellular geranylgeranyl pyrophosphate (GGPP),
not farnesyl pyrophosphate (FPP), and protein geranylgeranylation is diminished with no inhibition
of protein farnesylation. All three combinations of olefin isomers of digeranyl bisphosphonate are
biologically active with little loss of potency. Interestingly, of the four possible mono farnesyl
bisphosphonate isomers only those containing the (3E)-olefin are biologically active. This data
further supports our previous studies that show geranyl-containing bisphosphonates inhibit
geranylgeranylation, and shows for the first time that farnesyl containing bisphosphonates are also
biologically active.
(1)
Reference
Shull LW, Wiemer AJ, Hohl RJ, Wiemer DF. Synthesis and biological activity of isoprenoid bisphosphonates.
Bioorganic and Medical Chemistry, 2006, 14:4130-6.
286

P-39
PREPARATION OF NEW [1,4,2]-OXAZAPHOSPHINANES: POTENTIALLY
ANTIDEPRESSIVE AGENT
David Virieux, Jean-Noël Volle, and Jean-Luc Pirat
Laboratoire d’Architectures Moléculaires et Matériaux Nanostructurés ; Institut Charles Gerhardt,UMR 5253 ENSCM,
8 rue de l’Ecole Normale 34296, Montpellier cedex 5, France
Recently, our laboratory developed an original and diasteroselective strategy for the preparation
of new phosphinylated heterocycles: 2-aryl-[1,4,2]-oxazaphosphinanes 1. [1-5] These compounds
might be potentially of a great importance for agrochemical and pharmaceutical applications. [6,7] The
strategy adopted for the formation of these heterocycles 1 consists in a two step procedure: a
diastereoselective addition-cyclization reaction from methylphosphinate and the corresponding
-hydroxy-imine, followed by a pallado-catalyzed arylation.
R OH
H 2PO 2Me
Ph N Ph
R = H ou Ph
O
R OH H
* P
OCH3 *
Ph N Ph
H
t-BuOK
THF/toluene
O O
R O H Ar-X R O Ar
P Pd°(cat)
P
Ph N Ph
H
287
Ph N Ph
H
1
Ar = C 6H 5, p-MeO-C 6H 4, p-Br-C 6H 4, m-Cl-C 6H 4,
3,5-F 2-C 6H 4, 2-pyridine and 2-thiophene
Here, we propose the preparation of new oxazaphosphinanes 3 as potential antidepressive agents
(analogs to hydroxybupropion). Hydroxybupropion is a metabolite formed from well-known
Bupropion drug (Wellbutrin®), twice more selective toward the noradrenergic system than
Bupropion itself.
Me
Me
O
P
O
N
H
R'
Me
R' = H or Me, 3
Cl
Me
Me
O OH
N
H
Me
Hydroxybupropion
Cl
Me
O
Me
Me N
H
Me
Cl
Bupropion (Wellbutrin )
Reference
[1] Cristau, H.-J.; Monbrun, J.; Tillard, M.; Pirat, J.-L. Tetrahedron 2003, 44, 3183-3187.
[2] Cristau, H.-J.; Pirat, J.-L.; Virieux D.; Monbrun, J.; Ciptadi C.; Bekro, Y.A. J. Organomet. Chem. 2005, 690,
2471-2481.
[3] Pirat, J-L.; Monbrun, J.; Virieux, D.; Volle, J.-N.; Tillard, M.; Cristau, H.-J. J. Org. Chem. 2005, 70,
7035-7041.
[4] Pirat, J.-L.; Monbrun, J.; Virieux, D.; Cristau, H.-J. Tetrahedron 2005, 61, 7029-7036.
[5] Volle, J.-N.; Virieux, D.; Starck, M.; Monbrun, J.; Clarion, L.; Pirat, J.-L. Tetrahedron : Asymmetry 2006, 17,
1402-1408.
[6] Zhou, J.; Qiu, Y.; Feng, K.; Chen, R. Synthesis 1999, 1, 40-42.
[7] Wang, B.; Miao, Z.; Huang, Y.; Chen, R. Heteroatom Chem. 2007, 18, 65-69.
R

P-40
ANTITUMOR EFFECT OF BETAINE AND ITS IMPACT ON THE PHOSPHORYLATION
PROCESS OF RATS BEARING S180
Ji Yu-Bin 1 , Zhang Yu-Jin 2
1 Research center on Life science and environmental science of Harbin University of commerce,Harbin 150076, China;
2.
Postdoctal Research of the institute of Materia Medica of Harbin University of commerce
Helongjiang Harbin 150076, China
Objective: to study the anti-tumor activity of betaine and its effects on the phosphorylation
process of rats bearing s180. method: based on rats bearing s180 model, tumor inhibition rate,the
enzyme activity of acp and alp in serum are chosen as indexes, which are determined by the kit tests.
Results: the tumor inhibition rate of betaine of different dosages are 39.8%、25.7%、17.7%
respectively, betaine of high dosage can remarkably increase the activity of acp、alp, p

P-54
SYNTHESIS AND SEPERATION OF L-TRYTOPHAN OLIGO-PEPTIDES ASSISTED BY
PHOSPHORUS OXYCHLORIDE
Li Ma 1 ,Hai-ping Ren 1 ,Kui Lu 1* ,Yu-fen Zhao 2
1 School of Chemistry and Chemical Engineering, Henan University of Technology, Zhengzhou 450052 china; 2
Department of Chemistry, Xiamen University, Xiamen 361005 China
We have demonstrated that α-amino acids could be assembled into oligo-peptides with the
assistance of inorganic phosphorus [1] . the reaction products can be seperated by reversed phase
high-performance liquid chromatography(rplc) [2] . Similar results were obtained in the reaction of
l-trytophan (l-trp) and phosphorus oxychloride. Compared with different experimental condition ,
the results showed that the proper condition of direct synthesis was the molar ratio of l-trp and
pocl3 of 1 to 1, reaction temperature of 30℃, reaction time of 15 mins and in tetrahydrofuran as
solvent. Through the electrospray ionization mass spectrometry (esi-ms), a series of mass peaks
corresponding to oligo-peptides of l-trp were observed .the dipeptide trp-trp(m/z=391), as well as
cyclo-dipeptide cyclo-trp-trp (m/z=373) were purified by reversed rplc.
Scheme 1 showed the RPLC of the reaction products
This work was financial supported by National Nature Science Foundation of
China(No.20272055, 20572016) , Henan Province Science Foundation for Prominent Youth
(No.0312000900) and Office of Education of Henan Province (No. 2006KYCX017,
200510459015).
References
[1] Lu, K.; Liu, Y.; Zhou, N.; Chen, Y.; Feng, Y.-P. ; Guo, X.-F.; Chen, W.; Qu, L.-B.; Zhao, Y.-F.
Acta Chim. Sinica 2002,60,372 (in Chinese)
[2] Quan Bai, Xiao-juan Ge, Xing-du Gen. The purification of peptide in preparative scale with
reversed phase high-performance liquid chromatography. Chinese Journal of analytical
chemistry.2002,30(9),1126~1129.(in Chinese )
289

P-66
THIOUREIDO DERIVATIVES OF METHYLENEBISPHOSPHONIC ACID AS
POTENTIAL INHIBITORS OF ALKALINE PHOSPHATASES
M. Lozynsky a , A. Vovk b , A. Chuiko a , L. Kononets b , V. Tanchuk b , I. Muravyova b , V. Kukhar b
a b
Institute of Organic Chemistry, NAS of Ukraine, 02094, Kyiv-94, Ukraine; Institute of Bioorganic Chemistry and
Petrochemistry, NAS of Ukraine,02660, Kyiv-94, Ukraine
New substituted thioureidobisphosphonates were synthesized through the reaction of
aminomethylenebisphosphonic acid with corresponding isothiocyanates. The compounds obtained
were evaluated for their inhibitory activity on alkaline phosphatases in vitro.
Introduction of thioureido fragment in a structure of methylenebisphosphonic acid results in
improvement of inhibition of alkaline phosphatases from bovine intestine mucosa and human
placenta. Thioureidobisphosphonates were shown to have inhibition constants in the micromolar to
low millimolar range. The affinity of alkaline phosphatase from bovine intestine mucosa for
1-(3-phenylthioureido)methylenebisphosphonate as the most potent inhibitor is approximately an
order of magnitude higher than for 1-(3-аlkylthioureido)methylenebisphosphonate with methyl,
ethyl, tert-butyl or cyclohexyl substituents. 1-(3-Phenylthioureido)methylenebisphosphonate was
found to be better inhibitor than its derivative with substituents in benzene cycle. The results
suggest that the presence of thione group in the structure of inhibitor is also important for inhibitory
action since effect of 1-(3-phenylureido)methylenebisphosphonate on alkaline phosphatase activity
is considerably lower. To elucidate the binding modes several inhibitors were docked in the active
site of alkaline phosphatase from human placenta. The results obtained reveal that hydrogen bonds
play an important role in the interaction between thioureidobisphosphonate and the enzyme.
N
H 2
PO 3 H 2
PO 3 H 2
R-NCX
NEt 3
R
N
H
X
N
H
PO 3 H 2
PO 3 H 2
290
. n NEt 3
AcONa
AcOH
R
N
H
X
N
H
PO 3 HNa
X=S, O; R=Ph
X=S; R=Alk, Ar
PO 3 HNa

P-67
PHOSPHORYL SUBSTITUTED 3,5-BIS(ARYLIDENE)-4-PIPERIDONES POSESSING
HIGH ANTITUMOR- ACTIVITY
M.V. Makarov a , I.L. Odinets a , O.I. Artyushin a ,E.Yu. Rybalkina b , K.A. Lyssenko b , T.V. Timofeeva c , and M.Yu. Antipina, c
a b
A.N.Nesmeyanov Institute of Organoelement Compounds RAS, Moscow, Russia; Institute of Carcinogenesis, Blokhin
Cancer Research Center, RAMS, Moscow, Russia; c New Mexico Highlands University, Las Vegas, USA
3,5-Bis(arylidene)-4-piperidones (and related compounds) 1 possess anticancer activity [1a] and
reveal antioxidant properties. [1b] Some of these compounds are also fluorescent that makes possible
to use them as dyes for tracing their cellular pathways during chemotherapy and as agents for
photodynamic therapy. [2] The important way to regulate the bioavailability and drug delivery of
these compounds to target organs is an introduction of different substitutes R to the N-atom of a
piperidone moiety. Taking into account that phosphorus-containing groups are prospective as such
modifiers we would like to discuss the synthesis and “structure-activity-fluorescence properties”
relationship of phosphorylated arylidenepiperidones.
N-phosphorylated compounds 3 were obtained via direct phosphorylation by phosphorus(IV)
acid chlorides. Derivatives 4 with elongated alkylene-phosphoryl linker could be synthesized only
by condensation of aldehydes with phosphorylated N-alkylpiperidones as alkylation of the
precursor 2 with alkyl halides afforded surprisingly quaternary salts 5 as the only reaction products.
Compounds 3-5 and their pharmaceutically acceptable salts demonstrated high activity against
human lung carcinoma cell line A549 with IC50 values in the range of 0.3-15.0 M.
Financial support: Russian Basic Research Foundation (05-03-32692).
O
N
Y
+
H
C
O
O
R1 =R2 =OCH2CF3; OPh: R1 =Me, R2 Me2N O
N
P
R
NMe2 =OPh
2
R1
3
iii
Z
Z
1) i; 2) ii
O
N
H
2
291
Z
O
N
CH2X
Z N Hal
H2n+1Cn CnH 2n+1
5
i: HCl/AcOH or EtOH; ii: NaHCO 3/H 2O; iii: R 1 R 2 P(O)Cl/Et 3N/THF; iv: n-C nH 2n+1Hal/K 2CO 3/CH 3CN; n=1-4
Y=H
Y=CH 2X
Z
iv
O
4 X = (CH2) 2P(O)(OEt) 2:
Z = F, NO2, NMe2 n=1-4
References
[1]. a) Dimmock, J. R. at al. Eur J Med Chem, 2002, 37(10), 813. b) K.M.Yisef, M.A.El-Sherbeny,
Arch.Pharm.Chem.Lif Sci, 2005, 338, 181
[2] Nesterov, N. N. at al., Acta Cryst., 2003, C59, 605.
Z
Z

P-77
NEW POLYAMINES PHOSPHORAMIDATE VECTORS FOR GENE THERAPY
Mathieu Mével a , François Lamarche a , Jean-claude Clément a , Jean-jacques Yaouanc a , Laure Burel a , Philippe Giamarchi a ,
Tristan Montier b , Pascal Delépine b , Pierre Lehn b , Paul-Alain Jaffrès a , Claude Férec b .
a- CEMCA, UMR CNRS 6521, Faculté des Sciences et Techniques, Université de Bretagne Occidentale, 6 avenue Le
Gorgeu, 29238 Brest, (France) ; b-Unité INSERM 613, Institut de Synergie des Sciences et de la Santé, Université de
Bretagne Occidentale, avenue Foch, 29609 Brest cedex 2 (France)
DNA delivery into cells can be achieved by using synthetic vectors having the capacity to
compact DNA to form a cationic lipoplex which will have the suitable properties to go across the
cell membrane. The next step, will consists to liberate the DNA plasmid into the cyctoplasm
followed by its migration up to perinuclear region and finally across the nuclear membrane. The
chemical structure of the synthetic vectors can be classified into two categories: cationic polymers
(PEI, …) and cationic lipids. In our group, cationic lipids possessing structure inspired from
phospholipids present into membranes have been synthesized and tested for in vivo and in vitro
essays [1, 2, 3]. Of note, many cationic polymers (e.g. PEI) or cationic lipids (DOGS, DPPES, DOSPA),
identified by their transfection efficiency, are characterised by the presence of several amino
functional groups on their backbone. We endeavour the synthesis of cationic lipids having a
phosphoramidate lipidic moiety and a polyamino polar headgroup. For this study, the polar
headgroup is formed by the spermine as depicted below.
Reference
[1 ]J.C. Clément, P. Delépine, H des Abbayes, C, Férec, K. Le Ny, T. Montier, J.J. Yaouancfrench patent N°0214044
(2002), PCT n° FR0350116 (07/11/03).
[2 ]T. Montier, P. Delépine, K. Le Ny, F. Blanc, Y. Fichou, M. Le Bris, D. Gillet, E. Picquet, J.C. Clément, J.J.Yaouanc,
H des Abbayes, C. Férec, Recent Res.Devel. Chem., 2003,1, 41-58.
[3 ]T. Montier, P. Delépine, K. Le Ny, Y. Fichou, M. Le Bris, E. Hardy, E. Picquet, J.C. Clément, J.J. Yaouanc,C. Férec,
Biochimica et Biophysica Acta, 2004, 1665, 118-133.
292

P-79
SYNTHESIS AND DRUG RELEASE BEHAVIOR OF
UNSATURATED POLYPHOSPHOESTER
Qiu Jin-Jun, Bao Rui, Liu Cheng-Mei*
Department of Chemistry, Huazhong University of Science and Technology, Wuhan 430074
Polyphosphoester was a kind of biodegradable polymer with excellent biocompatibility, which
was investigated in drug delivery, gene carrier and tissue engineering [1] . A novel unsaturated
polyphosphoester(UPPE) containing fumarate segment in repeat units was first synthesizd by
condensation polymerization reaction (Scheme 1) [1] . Fumaric acid, 1,2-propylene glycol and
phosphorous oxychloride were used as the raw materials. Structure of the polymer was
characterized by FT-IR and NMR( 1 H, 13 C, 31 P). The novel unsaturated polyphosphoester could be
crosslinked in situ with N-vinyl pyrrolidone(NVP) for used as an injectable bone tissue engineering
scaffolds material.
Cl
O
P Cl + HO
CH3 O
O
O
OH
NEt3 O
P
O
O
CH3 O
CH3 Scheme 1 Synthesis of unsaturated polyphosphoester.
This paper reported the in vitro drug releases behavior of the crosslinking system of UPPE/NVP
with different contents of ciprofloxacin and different UPPE/NVP ratios (Table 1) in phosphate
buffer solution(pH 7.4) at 37 o C. The results indicated that the system with less content of
ciprofloxacin released more rapidly when the UPPE/NVP ratio was kept at a constant value, the
system with higher NVP/UPPE ratio released more rapidly when the content of ciprofloxacin was
kept at a constant value.
References
[1].Zhao Z., Wang J., Mao H.Q., Polyphosphoesters in drug and gene delivery. Advanced Drug Delivery Reviews 2003,
55:483–499.
[2]. Jin-Jun Qiu, Cheng-Mei Liu, Fen Hu, Xiao-Dong Guo, Qi-Xin Zheng. Synthesis of Unsaturated Polyphosphoester
as a Potential Injectable Tissue Engineering Scaffold Material. Journal of Applied Polymer Science, 2006, 102(4):
3095-3101.
293
O
CH 3
CH 3
O
O
O
O
O
CH3 n

P-80
IN VITRO DEGRADATION PROPERTIES OF UNSATURATED POLYPHOSPHOESTER
β-TRICALCIUM PHOSPHATE COMPOSITES
Qiu Jin-Jun, Bao Rui, Liu Cheng-Mei*
Department of Chemistry, Huazhong University of Science and Technology, Wuhan 430074
A novel unsaturated polyphosphoester(UPPE) was synthesized for used as an injectable bone
repair material [1] . From the point of chemical structure, polyphosphoesters are analogs of nucleic
and teichoic acids with excellent biodegradability and biocompatibility [2] . The phosphoester bond in
the polyphosphoester backbone can be cleaved by water and possibly enzymatic digestion under
physiological conditions. In this paper in vitro degradation property of the crosslinked composites
formed by UPPE, N-vinyl pyrrolidone(NVP) and β-tricalcium phosphate(β-TCP)(Table 1) was
investigated. The surface morphology of degraded sample was imaged by scanning electron
microscopy (SEM).
The results indicated that the UPPE/NVP/β-TCP crosslinked composite was degradable in
simulated body fluid. Mechanical property of degraded sample was close to that of human
cancellous bone, and surface of the degraded sample exhibited porous morphology which will
benefit to the attachment and growth of the osteoblast cell(Figure 1). The physical
parameters(sample mass, mechanical property, et al.) changed dramatically during the initial stages
of degradation. After 48 h of degradation, the physical parameters changed gradually due to the
slow degradation of the crosslinked networks.
Table 1 Formulation of UPPE/NVP networks evaluated in degradation studies.
Components
Formulation
UPPE NVP TCP BPO DMT
F1 1.0g 0.7g 0.6g 0.003g 0.005g
F2 1.0g 1.0g 0.6g 0.003g 0.005g
F1
Figure 1 Scanning electron micrographs of the F1 and F2 samples degraded for 120 days in SBF. The
micrographs were taken at 20000×magnification and the white bar within the image represents 1 µm.
References
[1].Jin-Jun Qiu, Cheng-Mei Liu, Fen Hu, Xiao-Dong Guo, Qi-Xin Zheng. Synthesis of Unsaturated Polyphosphoester
as a Potential Injectable Tissue Engineering Scaffold Material. Journal of Applied Polymer Science, 2006, 102(4):
3095-3101.
[2].Wang D.A., Williams C.G., Li Q., Sharma B., Elisseeff J.H. Synthesis and characterization of a novel degradable
phosphate -containing hydrogel. Biomaterials 2003, 24: 3969–3980.
294
F2

P-82
THE SYNTHESIS, ACID-BASIC AND MEMBRANE-TRANSPORT PROPERTIES OF
THE PHOSPHORYLATED AMINES
Rafael A. Cherkasov, Airat R.Garifzjanov, Maxim V. Khakimov, Alexey S. Talan and Gul’nara A. Ivkova
Kazan state university, Kremlevskaya, 18, Kazan, 420008, Russia
The row of the aminophosphates, α-, β- and γ-aminophosphonates and aminoalkylphosphates (I)
were synthesized by the classical methods of organophosphorus chemistry – via the Pudovik,
Kabachnik-Fields and Todd-Atterton reactions
The measuring of their acid-basic properties shows that all the compounds of the (I) structural
pattern have the lesser basic properties being compared with the corresponding primary and
secondary aliphatic amines. This circumstance can be explained with the strong
electron-withdrawing properties of the phosphoryl unit. The tendency of the bacisity increasing
parallel to the alkyl chain size growth is evident.
We have investigated the membrane-transport properties of the amines (I) in relation to the strong
mineral acid – perchloric acid and polybasic organic acids such as oxalic and tartaric. The transport
flow of the acids depends from the bacisity of the proton-accepting units of the molecule carriers
having the aminophosphonates and aminoalkylphosphates structures. Nevertheless
aminophosphates behave themselves more likely as the phosphoryl compounds, possessing the
lesser transport properties may be due the low bacisity of the nitrogen atom bound with the
phosphorus atom.
The mechanism of the membrane extraction is discussed. As we revealed it is different for the
each pair substrate-carrier and depend from the structure of the H-complexes formed. The influence
of the inner- and intramolecular H-bonds is also discussed.
The work was realized under financial support of RFBR (grant № 04-03-32906).
295

P-102
IDENTIFICATION OF SELF-ASSEMBLY PRODUCTS OF VALINE MEDIATED BY
PHOSPHORUS TRICHLORIDE BY ESI MASS SPCETROMETRY
Wenjie Zhao 1 Li Ma 1 Kui Lu 1 * Yufen Zhao 2
1.School of Chemistry and Chemical Engineering, Henan University of Technology, Zhengzhou 450052, China;
2.Department of Chemistry, Xiamen University, Xiamen 361005, China
Organic phosphorus reagents have been used in synthesis of peptides and cyclopeptides as
active and condensate reagents [1, 2] . Cyclopeptides are playing more and more important role in
biological modeling pharmaceutical design, nano- and molecular devices, biological sensors and
catalysts [3] . We have reported that a-amino acids could be assembled into homo-peptide libraries
with the assistance of phosphorus oxychloride or phosphorus pentachloride [4,5] . In our recent study,
Amino acids also could be assembled into 2~15 homo-peptides and homocyclic peptides by
phosphorus trichloride activation. ESI-MS/MS was used to study the products of reaction and
confirm the structures.
After the reaction of L-Valine(L-Val) with phosphorus trichloride for 48h then quenched with
H2O or various alcohols, the reaction mixtures yielded the corresponding peptides or peptide esters
and cyclopeptides, respectively. To confirm the product structures of homocylic peptides, the
MS/MS spectra of [M+H] + ions were investigated by collision-induced dissociation (CID) tandem
mass spectrometry. The main fragment ions of [M+H] + ion were [M+H-CO] + , [M+H-HCONH2] +
and [M+H-NHCHRCO] + . The protonated cyclo-peptide for valine could yield ions [M+1-28] + ,
[M+1-45] + , [M+1-99] + by stepwise loss of carbon monoxide, formylamine and a valine residue. For
example, the [M+H] + ion of cyclo-(Val)6 at m/z 595 produced the fragment ion at m/z 567
corresponding to [M+H-CO] + , the fragment ion at m/z 550 corresponding to [M+H-HCONH2] + , the
fragment ion at m/z 496 corresponding to [M+H-NHCHRCO] + . In the same way, the [M+H] + ion of
cyclo-(Val)5 at m/z 496 produced the fragment ions at m/z 468, m/z 451 and m/z 397, the [M+H] +
ion of cyclo-(Ala)5 at m/z 427 produced the fragment ions at m/z 399, m/z 382 and m/z 356,
respectively.
Acknowledgements: The authors would like to thank the financial supports from the Chinese
National Science Foundation (No.20272055, 20572016), Henan Province Science Foundation for
Prominent Youth (No.0312000900) and Office of Education of Henan Province (No.
2006KYCX017, 200510459015).
References:
1. C. J. Zhu, X. L. Yang, S. X. Cao , et al. Rapid Commun. Mass Spectrom., 2003,17,825.
2. S. Mc Murry, C.A. Lewis, N.V. Obeyesekere. Pept. Res., 1994, 7, 195.
3. D.T. Bong, T. D. Clark, J. R. Granja, et al. Angew. Chem. Int. Ed., 2001, 40 , 988.
4. N. Zhou, K. Lu, Y. Liu, et al. Rapid Commun. Mass Spectrom., 2002,16, 919.
5. H. Li, W. J. Zhao, S. X. Cao, et al. Chem. J. Chinese Universities, 2004, 25, 1866.
296

P-108
DISCOVERY OF ALKENYLPHOSPHORUS COMPOUNDS AS A NEW CLASS OF
CYTOTOXIC AGENTS FOR CANCER CELLS
Xiaohui Wang and Li-Biao Han
National Institute of Advanced Industrial Science and Technology Tsukuba, Ibaraki 305-8565, Japan; E-mail:
libiao-han@aist.go.jp
A series of Alkenylphosphorus compounds were synthesized and evaluated for anticancer activity
using several tumor cell lines. The results showed that HCC3 was the most potent anticancer agent
with IC50 values lower than those of the reference drug cisplatin. The cellular effects of the tested
compounds had much less cytotoxic effect on growth of NIH3T3 cells, while they produced
pronounced inhibition of S180 cell growth. Structure-activity relationship indicated that the double
bonds of the unsaturated phosphinoyl moiety was essential for the cytotoxic activity.
Alkenylphosporus compounds were further found to induce apoptosis in different cell lines as
evidenced by apoptotic ELISA assay.
297
Control
Treating with an alkenylphosphorus compound
This work was partially supported by New Energy and Industrial Technology Development
Organization (NEDO) of Japan (Industrial Technology Research Grant Program in 2004).

P-109
THE SYNTHSIS OF TRIPYRROLE PEPTIDE CONTAINING PHOSPHONYL
Li-feng Cao 1 , Li-li Shen 1 ,Ru-yi Zou 1 , Cun-jiang Liu 1 , Yong Ye* 1 , Xin-cheng Liao* 1 , Yu-fen Zhao 1,2
1 .Department of Chemistry, Key Laboratory of Chemical Biology and Organic Chemistry, Zhengzhou University,
Zhengzhou, 450052, China; 2 .The Key laboratory for Bioorganic Phosphorus Chemistry and Chemical Biology
(Ministry of Education), Department of Chemistry, Tsinghua University, Beijing 100084,China. *E-mail:
yeyong@zzu.edu.cn
Many research efforts have been aimed at targeting specific sequences in DNA with synthetic
ligands with the idea of designing both drugs and molecular probes for DNA polymorphism. Minor
groove binders are one of the most widely studied class of agents characterized by high level of
sequence specificity and they are still an interesting class of DNa ligands which demonstrate to
possess several biological activities [1-3] .
The tripyrrole peptide distamycin A is a naturally occurring antibiotic agent isolated in 1962 and
subsequently found having interesting antibacterial and antiviral activities. Our group had found
some phosphonyl amino acid have good biological activity[4]. In order to obtain high biological
activity compound, a series of tripyrrole peptide containing phosphonyl were synthesized. The
structures of these compounds was confirmed by 1H NMR, 31P NMR, MS and IR. The structure of
target compouond is shown at follow:
The title compounds were synthesized by 8 steps. The N-methylpyrrole containing nitro group
react with amino acid ester, then couple with dipyrrole carboxylic acid. To achieve the optimum
result of tripyrrole/amino acid ester conjugate, TLC was employed to monitor the progress of the
coupling reaction. After reduction of the nitro group in tripyrrole/amino acid ester conjugate, the
phosphonyl was introduced to it and title compound was formed. The activity of title compounds
are being continued.
Acknowledgments
The authors would like to thank the financial supports from NNSFC (No.20602032 and 20572061)
Reference
[1]. J. W. Trauger, E. E. Baird, P. B. Dervan, Nature, 1996, 382, 559.
[2]. S. White, E. E. Baird, P. B. Dervan, Chem. Biol., 1997, 4, 569.
[3]. J. M. Gottesfeld, L. Neely, J. W. Trauger, E. E. Baird, P. B. Dervan, Nature, 1997, 387, 202.
[4]. Y. S. Li, Y. F. Zhao, et al., Bioorganic & Medicinal Chemistry, 2000, 8, 2675.
298

P-142
DEVELOPING A SIMPLE ASSAY TO SCREEN FOR ORGANOPHOSPHATASES
Gareth Williams
Dstl Porton Down, UK, Email: grwilliams@dstl.gov.uk
Organophosphorus nerve agents could pose a hazard to both civilian populations and military
personnel, and improved post-exposure medical-countermeasures are potentially of interest. There
is also a drive to find improved decontamination methods especially ones that are
environmentally-benign. Enzymes could provide a novel solution.
There are already a number of enzymes known to catalyse the hydrolysis of organophosphates
such as phosphotriesterase (Pseudomonas diminuta), DFPase (Loligo vulgaris) and Human
Paraoxonase, PON1 (Serum paraoxonase family).
To find potential enzymes with high Kcat values, large libraries of mutated enzymes need to be
exploited, which necessitates the development of a simple high-throughput screen. This process is
commonplace in the pharmaceutical industry where vast quantities of compounds are screened
against one target enzyme, however our process is the reverse, and the target enzyme will be
modified rather than substrates.
This poster reports the synthesis of a number of fluorogenic nerve agent analogues that mimic the
parent nerve agents effectively, and are suitable tools for screening candidates for directed evolution
of efficient nerve-agent organophosphatases.
299

P-143
THE PHARMACOKINETICS ANALYSIS OF THE
PHOSPHORYL PEPTIDES IN MCF-7/ADR CELLS
Peng Zhang, Hongxia Liu, Zhenhua Xie ,Feng Liu, Mian Liu ,Yuyang Jiang*
The Key Laboratory of Chemical Biology, Guangdong Province, Graduate School at Shenzhen, Tsinghua University,
Shenzhen 518055, P.R.China Tel:86-755-26032094, Fax:86-755-26036087
E-mail:Jiangyy@sz.tsinghua.edu.cn
The modification (such as phosphorylation, methylation, acetylation and glycosylation) of amino
acids and peptides might have incurred a great improvement in their physiochemical property. The
oligopeptide N-diisopropyloxyphosphoryl- valine- phenylalanine-3,4,5- trimethoxyaniline(DIPP-Val-Phe-TMOA)
is a novel potential pre-drugs which has the function to induce
the apoptosis of multiple tumor cells. Now,we have developed a HPLC/UV method to study the
pharmacokinetics of DIPP-Val-Phe-TMOA in MCF-7/ADR cells. The peak concentration (Cmax)
of DIPP-Val-Phe-TMOA in MCF-7/ADR cells was up to 12.32 μg.mL-1 at 3.15h. The absorption
half-life(T1/2Ka) and elimination half-life(T1/2K) of DIPP-Val-Phe-TMOA was 2.67±0.05h
and 10.24±0.07h, respectively. The area under the cell concentration-time curve(AUC) was
203±0.456 μg.h.mL-1. It suggested that DIPP-Val-Phe-TMOA possessed higher hydrophobicity,
and could easily penetrate into the membrane of MCF-7/ADR cells. The results also revealed that
DIPP-Val-Phe-TMOA has better biological activity and longer half lifetime. These are consistent
with the results of biological experiments.
Acknowledgments
This work was supported by the National Natural Science Foundation (China, 20472043, 20572060,
20672068), the Project of Science and Technology of Guangdong Province
( 2005A11601008),Mega-Project of Science Research of Ministry of Science and Technology
(China, 2005CCA03400), the Natural Science Foundation of Guangdong Province (China,
06028200)
300

P-145
NEW PHOSPHORAMIDATE DICATIONIC VECTORS FOR GENE THERAPY
Mathieu Mével a , François Lamarche a , Jean-claude Clément a , Jean-jacques Yaouanc a , Laure Burel a , Philippe Giamarchi a ,
Tristan Montier b , Pascal Delépine b , Pierre Lehn b , Paul-Alain Jaffrès a , Claude Férec b
a- CEMCA, UMR CNRS 6521, Faculté des Sciences et Techniques, Université de Bretagne Occidentale, 6 avenue Le
Gorgeu, 29238 Brest, (France) ; b-Unité INSERM 613,, Institut de Synergie des Sciences et de la Santé, Université de
Bretagne Occidentale, avenue Foch, 29609 Brest cedex 2 (France)
It’s widely believed that gene therapy will become an efficient way for the treatment of
diseases such as cancer, cystic fibrosis and for vaccination. The essential requirements for gene
delivery are the transport of DNA through the cell membrane and ultimately the nucleus. Different
strategies have been used for the delivery of genetic material classified as viral or synthetic delivery
systems. The chemical structure of the synthetic vectors can be classified into two categories:
cationic polymers (PEI, …) and cationic lipids. In our group, cationic lipids possessing structure
inspired from phospholipids present into membranes have been synthesized and tested for in vivo
and in vitro essays1, 2, 3. To increase the condensation of DNA and to decrease the toxicity during
the transfection, we raised the number of cationic charges on our phosphoramidates as depicted on
the following scheme.
Reference
1.J.C. Clément, P. Delépine, H des Abbayes, C, Férec, K. Le Ny, T. Montier, J.J. Yaouanc, French patent N°0214044
(2002), PCT n° FR0350116 (07/11/03).
2.T. Montier, P. Delépine, K. Le Ny, F. Blanc, Y. Fichou, M. Le Bris, D. Gillet, E. Picquet, J.C. Clément, J.J. Yaouanc,
H des Abbayes, C. Férec, Recent Res.Devel. Chem., 2003,1, 41-58.
3.T. Montier, P. Delépine, K. Le Ny, Y. Fichou, M. Le Bris, E. Hardy, E. Picquet, J.C. Clément, J.J. Yaouanc, C. Férec,
Biochimica et Biophysica Acta, 2004, 1665, 118-133.
301

P-146
NOVEL CIDOFOVIR PRODRUGS: CONCEPTUAL AND SYNTHETIC STRATEGIES
Boris A. Kashemirov 1 , Joy Lynn F. Bala 1 , Xiaolan Chen 2 , Zhidao Xia 3 , R. Graham G.Russell 3 , and Charles E.
McKenna 1 *
1. Department of Chemistry, University of Southern California, Los Angeles, CA, 90089 USA.
2. Procter & Gamble Pharmaceuticals, Mason, OH, 45040 USA.
3. University of Oxford, Nuffield Department of Orthopedic Surgery, Nuffield Orthopedic Center, Headington, Oxford,
OX3 7LD UK.
Nitrogen-containing bisphosphonate (N-BP) drugs are widely used for the treatment of various bone diseases,
including osteoporosis and Paget’s disease. N-BPs, such as risedronate or zoledronate, inhibit farnesyl diphosphate
synthase (FDPS), which thereby prevents the prenylation of crucial GTPase proteins in osteoclasts. In addition, some
BPs and related phosphonocarboxylate (PC) analogs have demonstrated anti-neoplastic effects; however, these effects
are currently poorly understood. As a result, N-BPs and their PC analogs linked to imaging agents, such as fluorescent
labels, are an attractive target. Activated esters of fluorescent labels are typically conjugated to drugs containing
primary amines, therefore forming a stable amide bond. Parent drugs lacking this functionality further require structural
modifications to introduce an appropriate site for direct conjugation. Specifically, risedronate contains a pyridine ring
that is not chemically suitable for direct acylation by the fluorescent label. Herein, we report the first synthesis of a
fluorescently labeled analog of risedronate and similar labeling of other risedronate analogs. These syntheses include a
novel coupling strategy developed at USC utilizing linker moieties between the drugs and labels. The fluorescent
compounds have been evaluated in hydroxyapatite bone affinity assays.
302

P-147
FLUORESCENTLY LABELED RISEDRONATE AND RELATED ANALOGS: NOVEL
SYNTHESIS AND EVALUATION AS IMAGING PROBES
Larryn W. Peterson 1 , Boris A. Kashemirov 1 , John M. Hilfinger 2 , and Charles E. McKenna 1 *
1 Dept. of Chemistry, University of Southern California, Los Angeles, CA 90089 USA;
2 TSRL, Inc., Ann Arbor, MI 48108 USA
Cidofovir (HPMPC, 1) is a broad-spectrum antiviral agent that is used (Vistide®) to treat AIDSrelated CMV retinitis.
Cidofovir is of particular interest as a potential therapy for orthopox virus infections, and it is currently the only drug
approved for the treatment of smallpox. An important limitation of cidofovir as a therapeutic agent is its low oral
bioavailability resulting in poor transport into cells. In principle, the bioavailability of cidofovir can be increased by
using a prodrug approach; attachment of auxiliaries to the parent drug mask the negative charges allowing for increased
transport. Once inside the cell, the moiety is cleaved to release the active parent drug. We have recently synthesized two
new types of prodrugs incorporating benign peptide auxiliaries. The first prodrug 2 incorporates a Ser-containing
peptide at R1 with R2 = Et, while the second prodrug 3 uses a linker to a peptide at R1 with R2 = H. In our experience,
mono-esterification of the 1 phosphonate proved difficult as intramolecular cyclization intervened. Therefore, 2 was
synthesized from an intermediate in the synthesis of cidofovir. Dealkylation and debenzylation followed by conjugation
with the dipeptide afforded 2. 3 was synthesized by attaching an appropriate linker at R1 and subsequent conjugation
with a peptide. The detailed syntheses and preliminary biological evaluation of these novel cidofovir prodrugs will be
discussed.
303

P-149
SYNTHESES AND CHARACTERIZATIONS OF α-AMINOPHOSPHONIC ACIDS AND
THEIR DERIVATIVES
Fang Hua 1 , Fang Meijuan 2 , Liu Linna 1 , Zhao Yufen 1, 2 *
1The Key Laboratory for Chemical Biology of Fujian Province, Department of Chemistry, Xiamen University, Xiamen
361005, China.
2 Department of Pharmaceutical Science, Medical College, Xiamen University, Xiamen 361005, People’s Republic of
China, Xiamen University.
Compounds with phosphorus-containing structures are an important part of chemistry, because of
their applications in medicine fertilizers,pesticides and plant growth regulators.
-Aminophosphonic acids and their derivatives, as phosphorus analogs of amino acid, have
attracted much attention because they show widely biological activities. In this paper, the
compounds, (Benzoylamino-phenyl-methyl)- phosphonic acid dialkyl esters were synthesized.
Their structures were confirmed by IR, 31P, 1H, 13C NMR, MS and elemental analysis. The study
on the antibacterial and antitumor activities of these compounds was underway.
Compounds 2a-2g were synthesized as shown in Scheme 1 according to methods proposed in the
literature1.2. General procedures are shown as follows.
X
O
Cl +
R 1O
OR 1
P O
1
NH 2
304
Et 3N ice bath
CH 2Cl 2
R 1O
OR1 P O O
2a-2i
Scheme 1 Synthetic pathway of compounds 2a-2i
Compound 1 (1 mmol) was dissolved in dry dichloromethane (20
mL) to which triethylamine (0.4 mL) was added, and the solution was
added dropwise to 4-substituted benzoyl chloride (1.2 mmol) in
CH2Cl2 (10 mL). After 6 h completion of the reaction, the solvents
were removed under reduced pressure. The residue was added 15 mL
water and then extracted with ethyl acetate (3 × 15 mL), dried over
anhydrous MgSO4 and concentrated under vacuum. The residual
liquid was purified by silicon gel column chromatography (petroleum
ether/ethyl acetate = 2:1) to give compounds products 2a-2ias colorless
solids.
References
1. Takahashi H., Yoshioka M., Imai N., Onimura K., Kobayashi S. Synthesis 1994; 8: 763.
2. Villeneuve G. B., Chan T. H., TELEAY Tetrahedron Lett. 1997; 38 (37): 6489.
N
H
X
Comp. X R1
2a CH
i
Pr
2b N
i
Pr
2c COCH3
i
Pr
2d CCH3
i
Pr
2e CNO2
i
Pr
2f COEt
i
Pr
2g Cl
i
Pr
2h CH Et
2i N Et

P-150
LIGAND-PROTEIN INVERSE DOCKING AS A POTENTIAL TOOL IN THE
COMPUTER SEARCH OF PROTEIN TARGETS OF MYCOEDIKETOPIPERAZINE, A
NOVEL FUNGAL METABOLITE FROM A PAPULARIA SP.
Fang Meijuan 1 *, Fang Hua 2 , Ji Zhiliang 3 , Luo Shuna 2 , Zhao Yufen 1,2
1 Department of Pharmaceutical Science, Medical College, Xiamen University, Xiamen 361005, People’s Republic of
China, Xiamen University. E-mail: fangmj@xmu.edu.cn
2 Department of Chemistry, The Key Laboratory for Chemical Biology of Fujian Province, College of Chemistry and
Chemical Engineering, Xiamen University, Xiamen 361005, People’s Republic of China
3 Bioinformatics Research Group, School of Life Sciences, Xiamen University, Xiamen 361005
Fujian Province, PR china
Mycoediketopiperazine, a novel fungal metabolite from a Papularia sp., which was isolated from
a highly organicphosphorous polluted environment. Mycoediketopiperazine exhibited low potent
cytotoxic activity in the KB cell line (IC50 120 ug/mL) by the MTT assay protocol which was
adapted from that described by Mosmann. And it no shows antimicrobial activity. Owing to novel
structure of Mycoediketopiperazine and no find high bioactivity of the compound in experiments,
there is a need to develop a method for searching potential protein targets of Mycoediketopiperazine
to facilitate the prediction of unknown and secondary therapeutic target proteins and those related to
the side effects and toxicity of a drug or drug candidate.
An inverse-docking procedure called INVDOCK has been introduced to conduct
computer-automated inverse-docking searches of this database to identify potential protein targets
of a small molecule. Hence, Mycoediketopiperazine is investigated in this study. INVDOCK is a
ligand–protein inverse docking algorithm, which conducts computer-automated search of potential
protein targets of a small molecule by attempting to dock it to a cavity of each of these proteins. A
cavity is represented by a cluster of overlapping spheres that fill-up that cavity. This underlying
cavity database is generated from the protein 3D structures of protein data bank (PDB). The crystal
structure of Mycoediketopiperazine was used as the docked structure of ligand.
Mycoediketopiperazine is flexibly docked into the cavity by a procedure involving multiple
conformer shape-matching alignment of the molecule to the cavity.
Using the inverse-docking process, we found 456 putative protein targets to wich
Mycoediketopiperazine can bind or weakly bind. Figure 1 shows the ligand-protein interaction
energy E of all protein docked with Mycoediketopiperazine. Potential human and mammalian
protein targets strongly docked with Mycoediketopiperazine identified by INVDOCK are given in
Table 1 along with the respective ligand-protein interaction energy E (E≤-60 kcal/mol). The
ligand-protein interaction energy E that Mycoediketopiperazine docked to one of the identified
protein targets, RNA inhibitor substrate (PDB Id: 1a52) is -74.0 kcal/mol.
305

Tab. 1 Therapeutic targets of Mycoediketopiperazine identified by INVDOCK search (E≤-60 kcal/mol)
PDB Protein (HUMAN) Molecular Function E(kcal/mol)
1m5p RNA INHIBITOR SUBSTRATE none -74.0
1lzj GLYCOSYLTRANSFERASE B Transferring hexosyl groups -71.2
1imb INOSITOL MONOPHOSPHATASE Inositol or phosphatidylinositol phosphatase activity -70.6
1gzu
NICOTINAMIDE
MONONUCLEOTIDE ADEN
Nucleotidyltransferase activity -69.7
2bcu DNA POLYMERASE LAMBDA none -69.4
1m5o RNA SUBSTRATE none -68.7
1nn3
SIMILAR TO THYMIDYLATE
KINASE
Thymidylate kinase activity; ATP binding -65.9
1fos C-JUN PROTO-ONCOGENE none -63.4
1z0a
RAS-RELATED PROTEIN
RAB-2A
none -63.0
1ga5
ORPHAN NUCLEAR RECEPTOR
NR1D1
ligand-dependent nuclear receptor activity; zinc ion
binding; sequence-specific DNA binding
-62.8
1dlh HLA-DR1 none -62.3
1mck
IMMUNOGLOBULIN LAMBDA
LIGHT CHAI
none -61.2
1ef1 MOESIN Cytoskeletal protein binding -61.0
1ozu
SUPEROXIDE DISMUTASE
[CU-ZN]
Copper, zinc superoxide dismutase activity; metal
ion binding
-60.8
Fig. 1 Therapeutic targets of Mycoediketopiperazine identified by INVDOCK search
Reference
[1] Chen YZ, Zhi DG. Ligand-protein inverse docking and its potential use in computer search of putative protein
targets of a small molecule [J]. Pharm Ther, 2000, 86:191-198.
[2] Ji ZL, Wang Y, Yu L, et al. In silico search of putative adverse drug reaction related proteins as a potential tool for
facilitating drug adverse effect prediction [J]. Toxicology Letters, 2006, 164: 104-112.
306

P-151
SYNTHESIS OF MOPHOLINO OLIGONUCLEOTIDE WITH NORMAL PHOSPHATE
BACKBONE BY PHOSPHORAMIDITE METHODOLOGY
Pu-Qin Cai 1, 2 , Nan Zhang 2 , Chun Guo 1 , Pei-Zhuo Zhang 4 , Yu-Yang Jiang 1, 2 *, Yu-Fen Zhao 3
1
College of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang , 110016 , P. R. China
2
The Key Laboratory for Chemical Biology of Guangdong Province, Shenzhen Graduate School of Tsinghua
University , Shenzhen , 518055 , P. R. China
3
The Key Laboratory for Chemical Biology of Fujian Province, Department of Chemistry Xiamen University,
Xiamen , 361005, P. R. China
4
Shanghai GenePharma Co., Ltd. Suite 602,1011 Halei Road, Z.-J. High Tech Park, Shanghai 201203, P.R. China
With the development of the antisense, ribozyme, and RNAi technology, mRNA gradually
becomes a new drug target1, 2. However, application of natural oligonucleotides in vivo and their
possibility to be drugs still face several problems that have not yet been comprehensively settled.
For example, oligonucleotide delivery, stability in vivo, pharmacokinetics, and specificity will be
the major research fields in the future investigation. Chemically modified oligonucleotides are
developed to overcome these problems and have improved properties over natural oligonucleotides.
Several chemically modified oligonucleotides such as phosphorothioates, FANA, 2’-O-Me and
2’-O-allyl (Fig. 1) have been widely applied in oligonucleotide-based technologies being developed
as drug platforms including antisense, ribozyme, and RNAi3. We synthesized mopholino
nucleotides with normal phosphate backbones (Fig. 2) by phosphoramdite methodology. They
exhibit strong affinity with RNA oligonucleotide and high nuclease resistance which make them a
candidate to bring new features in the oligonucleotide-based technologies.
O
O
H
H
O
P
O
O
S
H
B
H
OH
O
O
H
H
O
P
O
O
O
F
B
H
O
O
Fig. 1: Structure of phosphorothioates, FANA, 2’-O-Me and 2’-O-allyl. B= Uracil, Cytosine,
Adenine, Guanine.
O
Fig. 2: Structure of mopholino nucleotides with normal phosphate backbones. B= Uracil, Cytosine,
Adenine, Guanine and Thymine.
References
[1] Alan Dove, Nature Biotechnology 20, 121 (2002).
[2] Simon W Jones et, al, Current Opinion in Pharmacology 4, 522 (2004).
[3] Hong-Yan Zhang et, al, Current Topics in Medicinal Chemistry 6, 893 (2006).
H
307
H
O
P
O
O
O
O
O
N
H
O
P O
O
B
H
B
O
O
H
H
O
P
O
O
O
H
B
H
O

P-152
ELECTROSPRAY IONIZATION MASS SPECTRA OF AMINO ACID METHYL ESTER
5'-PHOSPHORAMIDATES OF 2', 3'-ISOPROPYLIDENEURIDINE
Chen Wei-Zhu 1,2 , Gao Yu-Xing 2 2 *
, Zhao Yu-Fen
1 The Third Institute of Oceanography of The State Oceanic Administration, Xiamen 361005, P. R. China
2 The Key Laboratory for Chemical Biology of Fujian Province,Department of Chemistry, College of Chemistry and
Chemical Engineering, Xiamen 361005, P. R. China
Recently, O-nucleoside N-phosphoryl amino acids are continuing to be an important class of
rationally designed antiviral nucleoside prodrugs1 and the model molecules in the study of the
prebiotic biosynthesis of proteins.2 In the present work, we used Atherton-Todd3 reaction to
synthesize a series of amino acid methyl ester 5’-phosphoamidates of protected uridine. These
compounds were determined by positive-ion mode electrospray ionization mass spectrometry
(ESIMS) in conjunction with multistage tandem mass spectrometry. The fragmentation pathways
were investigated, and most of the fragment ions contained the phosphoryl group. It was interesting
that the methoxy group of amino acid methyl ester could migrate from the carbonyl group to the
phosphoryl group only for the sodium ion adduct, but not for the protonated molecule. The possible
formation mechanism was summarized in Scheme 1. Sodium ion could coordinate with phosphoryl
oxygen and carbonyl oxygen simultaneously to form a seven-membered ring. And the oxygen of
methoxy group might attack the phosphorus to form a five-membered pentacoordinated phosphorus
intermediate. Then, with the migration of methoxy group from carbonyl group to phosphoryl group,
the five-membered ring might break down by elimination of a neutral molecule CO. Finally, the
pentacoordinated phosphorus intermediate might lose one 2', 3'-isopropylideneuridine to produce
the ion at m/z 252. These results strongly suggested that metal ion, such as sodium ion, might play
an important role in the rearrangement.
O
H H
H3C O C C N
CH2 OH
HO P O
H3CO H
O C C NH
CH2 OH
ONa
HO P O
H 3CO
ONa
NH
CH
CH 2
OH
-CO
ONa
P O
OH
m/z 564
O
O
O
O N
O
O N
O N
O
NH
O
O
O
O
NH
NH
O
O
O
308
Na
O
O
P O
C OCH3OH CH NH
CH2 OH
ONa
H
HO P O
3C
O
H
O C C NH
CH2 -2', 3'-isopropylideneuridine
OH
O
ONa
O P OCH3 NH
CH
CH 2
OH
O
O
O N
O
O N
m/z 252
O
O
NH
NH
O
O
ONa
HO P OCH3 Scheme 1 A possible formation mechanism of rearrangement ion at m/z 252
Refrences
[1] McIntee E. J.; Remmel R. P.; Schinazi R. F.; Abraham T. W.; Wagner C. R. Probing the Mechanism of Action and Decomposition
of Amino Acid Phosphomonoester Amidates of Antiviral Nucleoside Prodrugs. J. Med. Chem. 1997, 40: 3323-3331
[2] Fu H., Li Z. L., Zhao Y. F., Tu G. Z. Oligomerization of N,O-Bis(trimethylsilyl)-R-amino Acids into Peptides
Mediated by o-Phenylene Phosphorochloridate. J. Am. Chem. Soc. 1999,121: 291-295
[3] Atherton F. R., Openshaw H. T., Todd A. R. J. Chem. Soc. 1945, 660-663
N
CH
CH 2
OH

P-153
SYNTHESIS AND BIOACTIVITY OF SIX-RING NUCLEOSIDE MODIFIED siRNA
Nan Zhang 1, 2 , Yue Wang 1, 2 , Pu-Qin Cai 2,3 , Pei-Zhuo Zhang 4 , Yu-Yang Jiang 1, 2 *, Yufen Zhao 1,5
1
Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Department of
Chemistry Tsinghua University, Beijing, 10084, P. R. China
2
Key Laboratory for Chemical Biology of Guangdong Province, Shenzhen Graduate School of Tsinghua University,
Shenzhen, 518055, P. R. China
3
College of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang, 110016, P. R. China
4 Shanghai GenePharma Co., Ltd. Suite 602,1011 Halei Road, Z.-J. High Tech Park, Shanghai 201203, P.R. China
5
Key Laboratory for Chemical Biology of Fujian Province, Department of Chemistry Xiamen University, Xiamen,
361005, P. R. China
Small interfering RNA (siRNA) molecules have drawn much attention since it can mediate target
gene expression in a variety of mammalian cells 1 . SiRNA works by Watson-Crick base-pairing of
an RNA guide sequence with target RNA followed by specific degradation of the target. There has
been considerable interest in harnessing the power of siRNA to treat human diseases such as cancer,
sepsis, and viral infections 2 .
However, therapeutic application of siRNA will be dependent on improvements in siRNA
stability, delivery, specificity and biological uptake. A number of chemically modified RNA have
been test in siRNA landscape, such as 2’-O-ally, 2’-deoxy-fluoro, LNA, boranophosphate, and
phosphorothioates 3 .
As far as I know, our group first synthesized several six-ring modified siRNA by phosphoramdite
methodology. They exhibit strong affinity with RNA and DNA and high nuclease resistance. The
further research of its bioactivity is in process in our lab. It introduces a new category of molecules
for potential use as RNAi-based therapeutics.
B
O
O
-O
309
N
O
P O
O
B =A,U,C,G,T
References
[1] Sayda M.Elbashir, et al, Nature, 2001,411,494
[2] RCC Ryther, et al, Gene Therapy, 2005,12, 5
[3] Barbara Nawrot, Current Topics in Medicinal Chemistry, 2006,6,913

P-156
A NOVEL SYNTHESIS OF
O-PHOSPHORYLATEDN-MENTHOXY-CARBONYL TYROSINE
Wang Tongjian 1 , Cheng Fang 2 , Tang Guo 1 , Zhao Yufen 1
1The Key Laboratory for Chemical Biology of Fujian Province and 2Key Laboratory of Analytical Sciences of Ministry
of Education, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, P.R.China
The phosphorylated tyrosine that consists in protein is a main existence that can respond to the
stimulation from the environment, so it plays an important role in life process[1]. The previous
methods to prepare the phosphorylated tyrosine which was consisted of two steps including oxidation
following phosphite [2] were based on the phosphite amine. In the recent research, Atherton-Todd
reaction has usually been used for the synthesis of O-phosphorylated N-Boc-tyrosine, but the method
has its limitations owing to the strict anhydrous condition and the poisonous carbon tetrachloride [3].
In this case, we took advantage of N,N’-Disuccinimidyl carbonate(DSC) to produce
N-Menthoxycarbonyl tyrosine and luckily we found it has the antibacterial efficacy. The key reagent
is trichloroisocyanuric acid which promotes the rapid conversion of dialkyl phosphites into their
dialkyl chlorophosphates[4] .The advantageous features of this reaction are the mild condition and
the simple operation. With the same method, we get a series of O-phosphorylated
N-menthoxycarbonyl tyrosine in a good yield (50%-70%).
O
O
P
O
H
Cl
O N O
Cl
N N
O
Cl
CH3CN
O
HO
O
P
O
1a~1c 2a~2c 3a~3c
a: diisopropyl phosphite ester (DIPPH)
b: dimethyl phosphite ester (DMPH)
c: diethyl phosphite ester (DEPH)
Cl
C
H2
References
[1].Fahad A. A. , J inzi J. W. , Kit S. L. . Biopolymers(Pep tide Science) [J ], 1998, 47: 197—203
[2].Kitas E. A. , Knorr R. , T rzecialA. et al. . Hel. Chim. Acta[J ], 1991, 74: 1 314—1 328
[3].Zhao Gang, Li Yanmei, Luo Shizhong, Han Bo, Zhao Yufen. Chemical Journal of Chineseuniversities
22(12),2034-2036
[4].Acharya, J.; Gupta, A. K.; Shakya, P. D.; Kaushik, M. P. Tetrahedron Letters (2005), 46(32), 5293-5295.
310
NH
CH
O
DBU
C
O
O
O
O
O
P
O
O
C
H 2
NH
CH
O
C
O
O
O

P-157
INHIBITION OF POKEMON GENE EXPRESSION BY ANTISENSE
OLIGONUCLEOTIDES
Nan Zhang 1, 2 , Yue Wang 1, 2 , Zhen-Hua Xie 2 , Yu-Yang Jiang 1, 2 *, Yu-Fen Zhao
1
Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Department of
Chemistry Tsinghua University, Beijing, 10084, P. R. China
2
Key Laboratory for Chemical Biology of Guangdong Province, Shenzhen Graduate School of Tsinghua University,
Shenzhen, 518055, P. R. China
3
Key Laboratory for Chemical Biology of Fujian Province, Department of Chemistry Xiamen University, Xiamen,
361005, P. R. China
Pokemon is an important transcription factor, which regulates the important tumor suppressor ARF.
Pokemon is overexpressed in multiple human cancers. Lack of Pokemon causes cellular senescence,
apoptosis, and blockage of differentiation. We designed and synthesized four 18-mer
phosphorothioate modified antisense oligonucleotides targeting the coding regions of Pokemon
mRNA, and investigated the down-regulation of Pokemon expression by measurement of the
fluorescence intensity of Pokemon-GFP fusion protein in COS-7 cell. Antisense oligonucleotide AS4,
which targets nucleotides 1496-1513 of Pokemon mRNA, was proven as the most potent compound.
As4 down-regulated the expression of Pokemon-GFP fusion protein to 22% at 40nm for 24hr.
Reference
[1] Barna M, Hawe N, Niswander L, Pandolfi PP. Nat Genet, 2000,25,166.
[2] He X, Dave VP, Zhang Y, et al. Nature, 2005, 433, 826.
[3] Costoya JA, Hobbs RM, Barna M, et al. Nat Genet, 2004, 36, 653.
[4] Ye BH, Cattoretti G, Shen Q, et al. Nat Genet,1997,16, 161.
[5] Koken MH, Reid A, Quignon F, et al. Proc Natl Acad Sci U S A,1997,94,10255.
[6] Chen WY, Zeng X, Carter MG, et al. Nat Genet,2003,33,197.
[7] Maeda T, Hobbs RM, Merghoub T, et al. Nature, 2005, 433.
[8] Maeda T, Hobbs RM, Pandolfi PP. Cancer Res, 2005, 65, 8575.
[9] Dove A. Nature Biotechnolog, 2002, 20, 121.
[10] Wang H, Parasad G, Buolamwini, et al. Curr Cancer Drug Targets, 2001,1,177
[11] Agrawal S, Kandimalla ER. Curr Cancer Drug Targets, 2001, 1, 197
[12] Opalinska JB, Gewirtz AM, Nat Rev Drug Discovery, 2002, 1, 503
[13] Hoen PAC, Rosema BS, Commandeur JNM, et al. Eur J Biochem,2002, 269, 2574
311
1, 3

P-158
ANTISENSE THERAPY TARGETING POKEMON ONCOGENE IN MCF-7 CELL
Nan Zhang 1, 2 , Wen-Peng Li 2 , Zhen-Hua Xie 2 , Yu-Yang Jiang 1, 2 *, Yu-Fen Zhao
1
Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Department of
Chemistry Tsinghua University, Beijing, 10084, P. R. China
2
Key Laboratory for Chemical Biology of Guangdong Province, Shenzhen Graduate School of Tsinghua University,
Shenzhen, 518055, P. R. China
3
Key Laboratory for Chemical Biology of Fujian Province, Department of Chemistry Xiamen University, Xiamen,
361005, P. R. China
This study was undertaken to investigate the role of Pokemon oncogene in MCF-7 (human
adenocarcinoma cancer) cells growth and the potential of Pokemon as a target for cancer therapy. An
18-mer antisense oligonucleotide AS4 (TTCAGGTCGTAGTTGTGG, targeting 1496-1513 site of
Pokemon mRNA) was proven as a potent inhibitor of Pokemon expression in our previous work. In
this study, we transfected AS4 to MCF-7 cells and confirmed the Pokemon mRNA and protein level
by RT – PCR and Western Blot. Furthermore, the cell cycle was analyzed by flow cytometer. G2/ M
arrest was observed when the cells were treated with antisense oligonucleotide at 100nM for 48 h.
We also found the P53 protein upregulation due to Pokemon inhibition. Our result suggests that
Pokemon inhibitor may be a novel approaches to human cancer therapy.
References
[1] Dove A. Nature Biotechnolog, 2002, 20, 121.
[2] Wang H, Parasad G, Buolamwini, et al. Curr Cancer Drug Targets, 2001,1,177
[3] Agrawal S, Kandimalla ER. Curr Cancer Drug Targets, 2001, 1, 197
[4] Opalinska JB, Gewirtz AM, Nat Rev Drug Discovery, 2002, 1, 503
[5] Barna M, Hawe N, Niswander L, Pandolfi PP. Nat Genet, 2000,25,166.
[6] He X, Dave VP, Zhang Y, et al. Nature, 2005, 433, 826.
[7] Costoya JA, Hobbs RM, Barna M, et al. Nat Genet, 2004, 36, 653.
[8] Ye BH, Cattoretti G, Shen Q, et al. Nat Genet,1997,16, 161.
[9] Koken MH, Reid A, Quignon F, et al. Proc Natl Acad Sci U S A,1997,94,10255.
[10] Chen WY, Zeng X, Carter MG, et al. Nat Genet,2003,33,197.
[11] Maeda T, Hobbs RM, Merghoub T, et al. Nature, 2005, 433.
[12] Maeda T, Hobbs RM, Pandolfi PP. Cancer Res, 2005, 65, 8575.
312
1, 3

P-162
THE POSITIVE AND NEGATIVE ELECTROSPRAY IONIZATION (ESI) MASS
SPECTROMETRY OF 1-(N-ETHOXYCARBONYLAMINO)
ARYLMETHYLPHOSPHONIC MONOESTERS
Yuan Ma*, Wei Liu, Yufen Zhao
Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Department of
Chemistry, Tsinghua University, Beijing 100084, China
1-Aminoalkylphosphonic acids are not only important phosphorus analogues of amino acids, but
also one type of naturally occurring amino acids. The positive and negative ion mass spectrometric
fragmentations of 1-(N-ethoxycarbonylamino)arylmethylphosphonic monoesters have been
investigated under electrospray ionization conditions. In the positive ion mass spectrometry, the
protonated title compounds predominantly eliminate a phosphite monoester via a four-membered
ring hydrogen rearrangement to yield protonated N-ethoxycarbonyl arylmethylimines as key
intermediate fragment ions, which could further undergo four-, six-, or eight-membered ring
rearrangements to produce mainly N-substituted/unsubstituted arylmethylimine ions. It is interesting
to note that the protonation of 1-(N-ethoxycarbonylamino)arylmethylphosphonicmonoesters
occurred in their arene rings. On the other hand, in the negative ion ESI mass spectrometry, the
deprotonated title compounds favored to initially form phosphonic-carboxylic mixed anhydrides as
the key intermediate fragment ions by loss of a molecular of ethanol, and they further eliminated CO
or CO2, respectively, to give rise to deprontonated three- and four-membered nitrogen and
phosphorus containing heterocyclic fragment ions.
Et
O
N P OR
ArH
O
OH
[M+H] +
+
O
H
O
OR
- HP
OH
313
Et
O N
+
ArH
Scheme 1. The initial positive-ion fragmentation pathway of the title compounds.
Et O
H
O
P
OR
O
O - Ar
N
[M-H] -
-EtOH
O
O
N -
Ar
O
P
OR
O

P-197
THE SYNTHESIS AND BIOLOGICAL EVALUATION OF BENZAMIDE RIBOSIDE AND
ITS PHOSPHORDIAMIDATE PRODRUG
Jianning Zhou 1,2 , Nan Zhang 1 , Chunyan Tan 1 , Jian Fan 1 , Chun Guo 2 & Yuyang Jiang 1*
1.The Key Laboratory of Chemical Biology, Guangdong Province, The Graduate School at Shenzhen, Tsinghua
University, Shenzhen 518055, China
2. School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, China.
Abstract: Benzamide riboside [BR, (1-β-D-ribofuranosyl) benzene-3-carboxamide], a novel
C-glycoside analogue of nicotinamide riboside, has been studied because of its excellent cytotoxic
activity. BR is metabolized intracellularly in malignant cells to its active metabolite benzamide
adenine dinucleotide (BAD), which inhibits the key enzyme of guanylate biosynthesis inosine
5 ` -monophosphate dehydrogenase (IMPDH), resulting in the inhibition of cell proliferation.
In order to overcome the problem of drug resistance and the first phosphorylation, we designed
and synthesized the benzylphosphordiamidate (1a) as the prodrug to deliver phosphorylated
benzamide riboside analogs into cells. However, the revaluation shows that 1a has lower
biological activity (IC50>200μM) compared to BR, which might be explained by the fact that 1a
could only serve as the BR depot form and could not be metabolized to the phosporylatd benzamide
riboside. The synthetic route of 1a is as follows:
HO
HO
O
HO
OH
D-Ribose
Br
O
HO OH
1
3
COOH
O
OH
NH 2
OBn
BnO
Br
4
HO
2
O
N
OBn
O
O
b O
c NHBn
O
d
O O
6
O
a
NH 2
BnHN
OBn
O
P
O
BnO OBn
5
O
314
OH
O O
7
N
O
O
HO
NH 2
BnHN
O
HO OH
1
O
P
O
NHBn
O
O
HO OH
Reagents and Conditions: a) nBuLi, THF, 5, -85 ℃ 3h;
b) (MeO)2CMe2, acetone, pTSA, rt; c) POCl3, Py, 0℃
8h then BnNH2, Et3N, rt, 2h; d) HCOOH/H2O, THF, 0℃.
Acknowledgement: We gratefully acknowledge the National Science Foundation of China
(20472043, 20572060, 20672068), the Project of Science and Technology of Guangdong Province
( 2005A11601008) for support of this work.
1a
NH 2
O
NH 2

Symposium 7
Phosphorus Chemistry in Agriculture, Industry and
Materials Science

KL-12
OVERVIEW ON OP METABOLISM CHEMISTRY AND ITS RELATIONSHIP TO
BIOLOGICAL AND TOXIC ACTIONS
Philip W. Lee
DuPont Agricultural Products, Experimental Station E402, Wilmington, DE 19880-0402, USA
Email: Philip.W.Lee@usa.dupont.com
Organophosphorus compound (OP) is a large diverse class of molecules with broad range of
chemical reactivity and biological properties. In addition to human drug activity, OPs are also
important agrochemicals and industrial chemicals such as flame retardants, plasticizers, and
catalysts. Organophosphates insecticides (such as dichlorvos, mevinophos) and chemical warfare
agents such as diisopropyl phosphorofluoridate (DFP) are potent acetylcholinesterase (AChE)
inhibitors. On the other hand, phosphorothioate esters (P=S) such as parathion, chlorpyrifos are
poor AChE inhibitors, but require metabolic activation to the corresponding oxon (P=O) for
insecticidal actions. The mode of action of glyphosate, the best known organophosphorus
herbicide, is the binding to 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS), thereby
inhibiting plant amino acid biosynthesis. Detoxification via N-aceteylation reaction is a proposed
mechanism to develop glyphosate resist crops. The mode of actions of organophosphate fungicides
compounds are not well defined, but apparently affect cell wall biosynthesis.
The metabolic oxidative desulfuration of phosphorothioate to the corresponding phosphate is one
of the most extensively studied metabolic reactions. This metabolic activation reaction, observed in
both chemical and biological systems, is catalyzed by cytochrome P450 enzyme, via the formation of
activated [P-S-O] intermediate. Other metabolic detoxification reactions involve chemical and
enzymatic hydrolysis of the phosphate esters. Inhibition of esterase enzymes have been identified as
the mode of action of delay neurotoxicity.
This presentation provides an overview of the chemical reactivity, metabolic pathway and mode
of toxic action of several selected OP compounds, and how these metabolic reactions affect the
biological activity and toxicity of this important class of chemicals.
315

IL-33
FOOD SAFETY: MONITORING OF ORGANOPHOSPHATE PESTICIDE RESIDUES IN
CROPS AND FOOD
Canping Pan
College of Applied Chemistry, China Agricultural University, Beijing 100094, P.R.China
Email: canpingp@cau.edu.cn
There are more than 40 major organophosphate (OP) pesticides used globally today, to control
wide range of insect pest species in agriculture, homes, gardens, and in veterinary practice. OP
insecticides exhibit potent acute and/or subchronic toxicity to mammals. Both OP and carbamates
insecticides are potent acetylcholinesterase (AChE) inhibitors and they are the first priority group of
pesticides reviewed under the US Food Quality Protection Act. US EPA had begun the risk
management program with the OP insecticides since August 1996. The final draft report on the
cumulative risk assessment of OP pesticides was issued in August 2006.
OP pesticide residues in crops, food and food-by-products (residues exceed the Maximum
Residue Levels MRL)is both a health and international trade issue. This is a difficult problem
especially the use and MRL of some of the key OP products are either withdrew or revoked recently.
This presentation provides an overview of the development of the OP residues analytical method at
the China Agricultural University (CAU) to monitor OP residues in crops and food in China. New
technologies, such as molecular imprinting (MIP) will be addressed in this presentation. Our
standard method includes solid phase matrix dispersion or GPC cleanup methods. A standard
protocol (NY/T 761), originally from US CDFA, was adopted. The current internationally accepted
and widely used “QuEChERS method” was also successfully validated at CAU on GCMS.
This presentation will discuss the residue analytical method design, GCMS and/or HPLC-MS
method validation and the storage stability of selective OP residues in crops and processed
commodities. Finally, the OP insecticides residues monitoring status in Chinese vegetables
collected in the past several years will be addressed.
316

IL-34
THE ROLE OF PHOSPHORUS IN CROP PROTECTION: EXPERIMENTAL AND
COMMERCIAL DISEASE AND WEED CONTROL AGENTS
Roger G. Hall
Syngenta Crop Protection, Switzerland
Although the importance of Organophosphate insecticides is steadily declining, Phosphorus still
plays an important role in Crop Protection. Glyphosate continues to dominate the herbicide market,
due in most part to the recent introduction of glyphosate-tolerant crops. The herbicide
Phosphinothricine, a smaller product in terms of sales, can also be used on crops engineered for
tolerance. But, where are the new Crop Protection products containing phosphorus?
Plants play a key role in the synthesis and production of important amino acids. Inhibitors of
amino acid biosynthesis which incorporate phosphorus in the molecule, offer excellent opportunities
to find new, selective weed control agents. For example, the phosphonic acids 1 are potent,
nanomolar inhibitors of the enzyme Imidazole Glycerol Phosphate Dehydratase and display
herbicidal activity. The phosphine oxide 2 has been reported to inhibit the enzyme Aceto Lactate
Reducto Isomerase and shows weak herbicidal activity. The phosphonic acid 3 inhibits the enzyme
Tryptophan Synthase and also shows herbicidal activity. We have also sought to prepare inhibitors of
Glutamine Synthetase such as 4 with more potent herbicidal activity than Phosphinothricine. It thus
appears that Phosphorus offers more opportunities to identify products for the control of weeds rather
than diseases. This lecture will discuss some recent research in these areas, and attempt to answer the
question raised above.
H
N
N
N
OH
R
1
R = CH2, O, NR 1 , S
S
OH
3
P(O)(OH) 2
P(O)(OH) 2
317
H3C P
O
H3C HO P
O
HO
OH
2
O
4
CO 2 H
NH 2
CO 2 H

IL-35
THE USE OF OP AND DEVELOPMENT OF NEW ORGANOPHOSPHORUS
AGROCHEMICALS IN CHINA
Hong-wu He
Key Laboratory of Pesticide and Chemical Biology, Ministry of Education; and College of Chemistry, Central China
Normal University, Wuhan 430079, China
Phosphorus-containing agrochemicals have made a major contribution to the advancement of
agriculture in China, because of their high efficacy and low prices. Almost 70% of agrochemicals in
China were organophosphorus compounds and 70% of phosphorus-containing agrochemicals were
insecticides during 1990 to 2002. OP insecticides have great economic importance for Chinese
Pesticide Industry, but the problem of them with toxicological problems or unacceptable residues in
the edible agricultural product have become as reasons for withdrawals of some OP insecticides from
the market of China. In order to meet the increasing China’s requirements on food quality/safety,
environment safeguard, the amount of high-toxicity OP products was limited from 2002 as the result
of policies from authorities in China. High-toxicity OP products are gradually being displaced by low
–toxicity OP products or other new synthetic agrochemicals.
China is emerging as the second largest country in pesticide production and usages. R&D for
environment friendly agrochemicals are becoming more and more important in China.
Agrochemical Research Center and innovation system were preliminarily established in China during
1996-2000 under the financial support from state government. R&D for new agrochemical has made
great progresses in recent years, 21 new agrochemicals as patent products have been developed and
got temporary registration from ICAMA. Several low toxicity organophosphorus compounds
including insecticide, herbicide, fungicide and anti-TMV agent are being developed in China.
α-(Substituted phenoxyacetoxy ) alkylphosphonate II as a kind of potential agrochemicals was
founded on the basis of the study of a series of α -oxophosphonic acid derivatives I in our Lab.
α-(Substituted phenoxyacetoxy ) alkylphosphonates showed a broad structure –activity-range. They
could exhibit much different biological activity such as plant growth regulating activity, insecticide
activity, fungicidal activity and herbicidal activity by the chemical modification of substituents in
parent compound. Such as some compounds II exhibited notable herbicidal activity[1,2]and were
demonstrated as a effective inhibitor of pyruvate dehydrogenase complex from plant ( in vitro )*. In
order to evaluate the commercial potential as herbicide, some compounds with low acute toxicity
were evaluated in the field. Field tests showed that they exhibited a potent activity against
broad-leaved weeds at the rate of 150-450g /ha in lawn, wheat and zeamx field.
Acknowledgments
Financial support by National Basic Research Program of China (2003CB114400) and NNSFof
China ( 20372023)
References
[1] H.W.He and Z.J.Liu, Chinese Journal of Organic Chemistry, 2001, 21 (11), 87
[2] H.W. He*, T. Wang and J. L. Yuan, Journal of Organometallic Chemistry, 690, 2005, 2608-2613
318

IL-36
CURRENT STATUS OF ORGANOPHOSPHORUS
INSECTICIDE AND STEREOCHEMISTRY
Mitsuru Sasaki
Division of Bio-systems Chemistry, Graduate School of Science and Technology,Kobe University, Kobe, Hyogo
657-8501, Japan . E-mail: msasaki@kobe-u.ac.jp
Organophosphorus agrochemicals including organophosphorus insecticide are still useful tools for
crop protection. For instance, organophosphorus insecticides have been widely used in terms of
their cost/performance with broad insecticidal spectra.
There are organophosphorus agrochemicals having chirality at the phosphorus or at the carbon
center in the molecule. The importance of chirality in organophosphorus agrochemicals is well
recognized in most aspects of their chemistry, biochemistry, biology and toxicology.
Thus reviewing the synthesis, selective toxicity and stereoselectivity of organophosphorus
agrochemicals not only organophosphorus insecticide but also organophosphorus fungicide or
herbicide will be firstly done on the following topics; absolute configuration-insecticidal activity
relationships of the enantiomers of organophosphorus insecticides, asymmetric rule on the AchE
inhibition by organophosphorus insecticides, and biological activity of the optical isomers of some
phosphoramidothioates and 1-hydroxyethylphosphinic acid.
Then recent developments on the methodology for preparing optically active phosphorus
compounds having biological activity will be discussed in terms of asymmetric synthesis of
organophosphorus synthetic intermediates with asymmetric induction at phosphorus center in the
molecule, conformational analysis of phosphorus-containing heterocycles, and stereochemical course
in the conversion of 1-aminoalkylphosphonic acids to 1-hydroxyalkylphosphonic acids.
319

IL-37
GLOBAL USE OF ORGANOPHOSPHORUS PESTICIDES
William H. Hendrix, III,
Technical Expert, Dow AgroSciences, Indianapolis, IN USA
Organophosphates (OP) are the most widely used class of insecticides in the world and have
helped revolutionize insect control. Providing broad spectrum insect control they are used in the
home, the garden, in agriculture, and in veterinary practice. Despite challenging regulatory pressure,
they continue to see new uses and formulations that increase their efficacy, selectivity and safety.
History
First recognized in 1854, the insecticidal properties were not defined until Tetraethyl
pyrophosphate (TEPP), which was developed in Germany during World War II as a by-product of
nerve gas development. In the 1940’s, the first wave of commercially available OPs, including
parathion, reached the market. In 1965, the world’s most widely used OP, chlorpyrifos, was
introduced. Today, we continue to see new uses and formulations being developed in all major
markets.
Distribution
OPs are manufactured by most multinational companies and many regional generic manufacturers.
There are roughly 100 OPs registered for use around the world and, in general, they are used in every
country. It is important to remember that all OPs are not alike. There is considerable variation
especially in toxicity classifications. Although some countries are phasing out or reducing most OP
use, many other countries, such as China, are moving to phase out only the more toxic (Tox Class 1)
molecules. External influencers impacting the sale and distribution of OPs include government
regulators, food chain, and health/environmental non-governmental organizations.
Major Markets
OP molecules are used to protect man, his crops, and his home in a variety of ways. Their
formulation flexibility and broad spectrum control have made them popular choices for a variety of
uses. For example, OPs have been used for vector control as a fog, as a wall treatment or
incorporated into the plastic used for bed netting in addition to their more traditional uses in
agriculture. The major markets will be examined by country and by use pattern contrasting changes
over time.
New Developments
As farming continues to adapt to provide more sustainable options, so have the OPs. Because of
increasing concerns over residues, application timing has been scrutinized to make sprays as dormant
or early season applications. New formulations and delivery options have been developed to increase
handler safety or to mitigate environmental concerns. Microencapsulated formulations, for example,
have increased safety profiles, reduced odor and dust, all while providing enhanced control.
Because of their broad-spectrum control, formulation and application flexibility, OPs will continue to
have an important insect management tool for the foreseeable future.
320

O-85
“GREEN” WAYS OF PHOSPHORUS COMPOUNDS PREPARATION
Budnikova Yu.H. a* , Krasnov S.A., Graznova T.V., Tomilov A.P. b , Turigin V.V. b , Magdeev I.M.. a , Sinyashin O.G. a
a Institute of Organic and Physical Chemistry of Russian Academy of Sciences, Kazan, Russia
b GOSNIIOHT, Moscow, Russia. E-mail: yulia@iopc.knc.ru
The existing industrial technology of synthesis of organophosphorous compounds is obsolete, as it
is based on the use of chlorine and chloride of phosphorus thus causing serious environmental
problems and main expenses of manufacture. Electrolysis presents a promising technology for
chemical conversions under ambient conditions without the use of either toxic or hazardous reagents;
it can minimise both the number of chemicals employed and the number of byproduct streams. The
new general electrochemical one-phase way was developed for the of phosphorus compounds
preparation, such as tertiary and primary phosphines, trialkyl phosphates, including trioctylphosphate,
phosphorous and hypophosphorous acid, etc. Scientific foundations for new electrochemical
technologies with obtaining pilot lots of substances and materials from white phosphorus were
developed.
C athode A node
R O -
P 4
+ 2 e -2 e
P 4
R'
+ n e
Pb-cathode
in situ
R O H
(H 2 O )
(R O ) 3 P O
[(i-R O ) 2 P ( O ) ] 2 O
H 3 P O 3
RPH 2
CH 3 COOK/CH 3 COOH
+ n e
Pb-cathode
321
[P H 3 ]
I -
I +
R'
DMSO/KOH
90% or
80% or
80%
R 3 P
M n+ L + ne M 0 L L = bipy, solvent
M 0 L + P 4 product [M-P]
Cathode
+2e
Zn0
PhX
Zn2+
PhZnX
P 4
Zn2+
Ph3P (80%)
Anode-Zn
-2e

Construction of the integrated laboratory electrolyzer of filter-press type
Acknowledgments: RFBR (04-03-32830, 05-03-08039 ofi-p), INTAS.
Reference
[1] Budnikova Yu.H., et all. J.Organomet.Chem., 690, 2416-2425, 2005
[2] Patents for inventions RU №№ 2199545, 2221805
322

O-86
PHOSPHATE - AN IMPORTANT ELEMENT IN THE AGRICULTURAL AND
ENVIRONMENTAL SPHERE
Dirk Freese
Brandenburg University of Technology Cottbus P.O. Box 101344, D-03013 Cottbus, Germany E-mail:
freese@tu-cottbus.de
The Phosphate Cycle Phosphate is indispensable for all forms of life because of its genetic role in
ribonucleic acid and function in energy transfers via adenosine triphosphate. In natural ecosystems
P is usually the life-limiting element due to its low availability. Of the Phosphate in the
soil-plant-animal system, commonly over 90% is in the soil and less than 10% enters the
plant-animal life cycle. Phosphate taken up by plant roots is either in the H2PO4 - or HPO4 2- form.
The amount of each form present depends on the soil solution pH. At pH 7.22 there are equal
amounts of these two forms. Below this pH, H2PO4 - is the main form. Soluble P fertilisers applied
to the soil are very rapidly changed to less-soluble compounds that, with increasing time, become
less and less available to plants.
Phosphate as an essential element of life is involved in versatile processes of terrestrial and
aquatic environments. Considering the use of P in agriculture its application as fertilizer to arable
lands often improves crop production. But the extent of P fertilisation varies considerably between
developing countries and industrial nations. In general, P deficiency in agriculture is typical of the
first group, whereas high application rates of P fertilizer in the latter one have induced some
environmental issues. In most of sub-Saharan Africa, where per capita food production as been
declining in recent years, fertilizer additions of this element for food crops are fraction of the rate of
removal of phosphate in the harvested crops. The soils have been mined of phosphate for years,
with the result that in many areas lack of this element is the first limiting factor in food-crop
production. On the other side the continued application of P fertilizer can produce detrimental
effects in both the terrestrial and aquatic environments. But in any discussion of the impact of soil
and fertilizer Phosphate on the environment, the detrimental effects must be considered along with
the benefits
In modern agricultural economies there are two aspects that should be taken into account: saving
utilisation of the limited resources of rock phosphates and fertilisation practices have to be geared to
both the optimal plant nutrition and a sustainable land use as an important part of environmental
protection policies.
Forms of Phosphate in soil
Inorganic and organic P fertilisation over the last decades lead to a considerable P accumulation
in soils. The total P content in soils is in the range 100 to 3000 mg/kg almost entirely as
orthophosphate. The proportion of P in solution is only

Fate of Phosphate to soils: Sorption
The phosphate sorption process in soils can be subdivided into three categories: adsorption as the
binding of P on the surfaces of solid soil constituents, diffusion of P into solid soil constituents and
precipitation as the forming of a P-rich solid phase. In the literature the term sorption is used instead
of adsorption because it covers the fast surface reaction of adsorption and the long term reaction.
The kinetics of P sorption has received considerable attention over the past years. The initial fast P
sorption kinetics is presumably due to reaction with the surface sites of metal (hydr)oxide particles
that are exposed to the solution phase. The slow reaction may be due to a slow diffusion into
aggregates or due to the slow formation of phosphate containing mineral phases. The reversibility
of P bound to soil is of interest with respect to both bio-availability and the risk of pollution of
surface waters as a result of P run-off rather then translocation of P to deeper soil layers.Predicting
the availability of P in soils: Desorption
The assessment of phosphate bioavailability in soils and sediments is of interest in both
agricultural and environmental systems. In agricultural soils, there is a need to predict the quantity
of P that is available for plant growth, as opposed to the total amount of P in soil.
In terms of biological availability, soil P is commonly divided into the following forms: i)
directly soluble P (labile P), ii) reversibly adsorbed P and iii) strongly bound ("irreversibly fixed") P.
In order to characterise P forms in soils and their bioavailability, a wide variety of methods have
been proposed during the last few decades and the discussion about is still going on.
Therefore some new methods will be presented especially designed to obtain a proper
understanding of long-term soil P desorption kinetics. These approaches are suitable to discriminate
between fast and slow pools of P release in soils.
324

O-88
PHOSPHATE REMOVAL AND RECOVERY WITH CALCINED LAYERED DOUBLE
HYDROXIDES AS AN ADSORBENT
Liang Lü a, b* , Zhaoliang Zhou a , Jing He b , Yulin Wang a , Guoqiang Wu a
a
West Branch of Zhejiang University of Technology, Zhejiang 324000, China
b
State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology, Beijing 100029,
China. E-mail: lianglv_qzxy@126.com; Fax: +86 570 8026549; Tel: +86 570 8026668
Organic pollution in closed water bodies such as bays and lakes has been increasing by
eutrophication, and removal of nutrient salts from the receiving water is an important consideration
to control eutrophication. A major source of nutrient salts is domestic wastewater. A large amount of
used phosphate finally reaches water environment as diluted waste, which often leads to pollution
of the water environment. Phosphate is recognized as being one of the resources that will be lost in
near future. It is of value to collect the finally disposed phosphates from effluents and drain water
before further dispersion and dilution of them in the water environment. An adsorption process has
been applied widely to treatment containment water, because the process has some advantages, such
as less production of sludge and easy operation. A variety of adsorbents have been developed for
phosphate removal, such as aluminum oxide, iron oxide, zirconium oxide, basic yttrium carbonate,
and fly ash.
Layered double hydroxides (LDHs), are a class of synthetic anionic clays whose structure can be
described as containing brucite-like layers in which some of the divalent cations have been replaced
by trivalent ions giving positively-charged sheets. This charge is balanced by intercalation of anions
in the hydrated interlayer regions. The general formula is [M 2+1-x M 3+x (OH) 2 ] x+ (An - ) x /n·mH2O,
where M 2+ and M 3+ are metal cations for example Mg 2+ and Al 3+ , that occupy octahedral sites in the
hydroxide layers, An- is an exchangeable anion, and x is the ratio M 3+ /(M 2++ M 3+ ) and the layer
charge will depend on the M 2+ /M 3+ ratio. The sorption of anions from aqueous solutions by
structural reconstruction of calcined LDHs (denoted CLDH) is based on a very interesting property
of these materials, the so-called memory effect. In our previous work, it was also indicated that the
calcined LDH can effectively removal toxic anions (such as fluoride, chloride, bromide, and
perchlorate) from water.
In this work, the adsorption properties of CLDH for phosphate and the method of regeneration of
this material were examined. The influences of CLDH structures, adsorbent dose, initial fluoride
concentration, temperature and co-existing anions on the removal of fluoride have been investigated.
It has been found that the LDHs with Mg/Al molar ratio of 2 represented the highest capacity to
remove phosphate ion from aqueous solution at pH 6.0. Phosphate adsorbed on the CLDH was
effectively desorbed at NaCl solution and the CLDH were reconstruction to LDH at the same time.
The regenerated LDH could be calcined and reused repeatedly for the phosphate removal.
Phosphate in the exhausted desorption solution was recovered as calcium phosphate by precipitation
with Ca 2+ . The results suggest the possibility of an effective system for phosphate removal and
recovery, which includes the following processes: adsorption, desorption, recovery of phosphate,
and regeneration of the CLDH.
325

O-89
DEVELOPMENT, SCALEUP AND COMMERCIALISATION OF CATALYST LIGNDS
Ranbir Padda and Gordon Docherty
Rhodia UK Limited, P.O. Box 80, Trinity Street,
Oldbury, West Midlands, B694LN, United Kingdom.
Phone, +44-(0)-121-541-3278; Fax, +44-(0)-121-541-3346.
E-mail:ranbir.padda@eu.rhodia.com
Catalyst ligands are continually being developed by the academic community and industry with
ever increasing turnover numbers, higher enantioselectivities etc. The types of catalysts and their
scope of application are an immense area of activity e.g. child catalysts, achiral catalysts,
phosphorus-based, nitrogen-based, phosphorus and nitrogen containing and so forth.
Phosphine catalysts are a very important class of catalysts and we report on the development,
scal-up and commercialisation of a number of ligands by Rhodia over the last 10 years. Recent
examples include MeDuphos, patented by Dupont1, tetra-butyl diphosphiuo xylene patented by ICI2
and BINAP (originally developed by Takasago). An in-depth discussion will highlight factors for
consideration when developing and scaling-up synthesis of these ligands on an Industrial scale.
References
1. Patent US005008457 and US005329015A
2. Patent WO 99/47528 and WO 99/47528
3. Patent JP59020294(A2.
326

O-90
BLEACHING CHEMISTY OF TRIS(HYDROXYMETHYL)PHOSPHINE AND
TETRAKIS(HYDROXYMETHYL)PHOSPHONIUM SULFATE
Thomas Q. Hu a , Brian R. James b , Richard Chandra b , Eric Yu b and Dmitry Moiseev b
a Pulp and Paper Research Institute of Canada, Vancouver, BC, Canada V6S 2L9
b Department of Chemistry, Univ. of British Columbia, Vancouver, BC, Canada V6T 1Z1
Research Institute of Canada, 3800 Wesbrook Mall,Vancouver, BC, Canada V6S 2L9.
Phone: 1-604-222-3235; Fax.: 1-604-222-3207; E-mail: thu@paprican.ca
Bleaching of lignin-rich wood pulps, an important industrial process for the production of
low-cost papers, involves the non-selective, oxidative removal and/or reductive modification of
lignin chromophores such as lignin coniferaldehyde and methoxy-pbenzoquinone. During our
studies of a H2O-soluble, coppertris(hydroxymethyl)phosphine (THP) complex, Cu-P(CH2OH)3, as
catalyst for the selective, H2-bleaching of such pulps, we discovered that the phosphine itself was an
effective bleaching agent over an extremely wide range of process conditions. We also found that
the commercially available tetrakis(hydroxymethyl)phosphonium sulfate (THPS),
[P(CH2OH)4]2SO4, was equally effective. To support the commercialization of THPS as a bleaching
agent for the paper industry, we have studied the aqueous reactions of THP with lignin model
chromophores and isolated milled wood lignin. We have also determined the fate of phosphorus in
the bleaching of a spruce thermomechanical pulp with THPS. This presentation will describe the
results of these studies and discuss the potential application of THPS as a bleaching agent for the
paper industry.
327

O-91
USE OF ION EXCHANGE COMPOSITES BASED OF TITANIUM AND ZIRCONIUM
PHOSPHATES FOR CLEANING OF WATER SOLUTIONS
Valery P. Nesterenko
Belarusian National Technical University
65, Nezavisimosty Avenue, 220027, Minsk, Republic of Belarus. E-mail: v.nesterenko@mail.ru
In many cases creation of the effective systems for the cleaning of water solutions, polluted with
radioactive elements and heavy metals, for example, realization of processes of extraction of
radionuclides from wastes, deactivation and cleaning of wastewater, water preparation, is connected
with necessity of use of sorption materials with given properties. Sorption processes have the
advantages before other methods (for example, such as evaporation and precipitation), as they are
more effective at large volumes of solution, do not bring in the difficulties, caused by corrosion of
the equipment and in majority of cases provide additional clearing of corrosive impurity and
products of division.
The present work is dedicated to development of approaches for preparing, studying and using of
new ion exchange composites. The thin layers of Ti(IV) and Zr(IV) phosphates have been
synthesized by the method of ion molecular layering on the surfaces of carbon matrices.The
obtained pellicular materials represent ionites similar to the Nucleosil ionites (Germany)due to a
number of their properties. pH range of ionites functioning on a Ti(IV) phosphate base equals 1-8,
on the base of Zr(IV) phosphate – 1-10. Physicochemical properties of the synthesized ion
exchangers have been investigated by modern methods. Comparative characteristic of adsorption
properties has been determined for a series of heavy metals. For example, statical exchange capacity
of Titanium phosphate ionite (pH 2-7, 10-3 M solutions)of UO22+, Fe3+, Cd2+and MoO42- - ions
is in the range of 0.1-1.8 mequ/g. It has been established that Zirconium phosphate ionites have
1,5-2,0 times higher sorption activity asregards cations of d- and f-elements. Under the dynamical
conditions, the processes of sorption and elution of the Pb2+ - ions have been studied on Zirconium
phosphate ionite. Thus,the dynamical sorption capacity for 0,025 M Pb2+solution has been 130,5
mg/g.
The advantages of the synthesized phosphates ionites are the following: selectivity to the ions,
forming heteropoly acids P(V), a greater (by one order) rate of establishing ion exchange
equilibrium, saving of phosphates modifying agent. Realisation of ion exchange processes with
application of the developing ionites is rather simple, which is notably important while extracting
radionuclides. The synthesized ion exchangers are of represent practical interest because of their
high radiation immunity and resistance to leaching. They may be employed with a view to ensure
security of the environment as well and in case of their burial after utilization.
It may be possible to use these ionites in processes of cleaning of sewage, extraction of value
metals in hydrometallurgy as well as in other ion exchange technologies.
References
[1] V.P. Nesterenko. Invention Certificate No 623286 (1978).
[2] V.P. Tolstoy. Uspekhi Khimii, 62, release 3, 260 (1993).
[3] V.P. Nesterenko et al. Third International Technical-Practical Conference "Productive Reuse of Former Military Sites:
Environmental and Economic Aspects of Demilitarization". Republic of Belarus, U.S. Department of Defense, Minsk
(1996).
328

O-92
SELECTIVE CHROMIUM OLIGOMERISATION CATALYSTS WITH VARIOUS
PHOSPHORUS LIGANDS
Kevin Blann, John T. Dixon, Esna Killian, Hulisani Maumela, M., Chris Maumela, Ann E. McConnell, David H. Morgan,
Mari_ Pretorius, Henriette de Bod, William Gabrielli, Alex Willemse, Pumza Zweni, Palesa Nongodlwana
Sasol Technology (Pty) Ltd., R&D Division, 1 Klasie Havenga Road, Sasolburg 1947, South Africa
kevin.blann@sasol.com
Conventional ethylene oligomerisation reactions generally produce a mathematical distribution of
LAO’s (linear alpha olefins). Since the market demand for each olefin cut differs, it remains an
imperative in the co-monomer industry to develop new technologies for the selective
oligomerisation of ethylene to valuable 1-alkenes such as 1-hexene[1] and 1- octene.[2] An added
advantage of this approach is to have an oligomerisation system that is flexible in producing a
specific 1-alkene as dictated by market demands.
We report herein, a family of chromium-based catalyst systems utilising an array of phosphine
ligands for the production of linear alpha olefins. Depending on the unique characteristics of the
ligands utilised,[3][4] these catalysts can be tailored to provide unprecedented control over reaction
selectivity. A detailed study on the requisite catalyst synthesis and modifications for these selectivity
switches will be presented.
1)Cr(Ⅲ)
2)Ligand
3)Activator
Reference
[1] Dixon, J.T., Green, M.J., Hess, F.M., Morgan, D.H. J. Organomet. Chem. 2004, 689, 3641.
[2] Bollmann, A., Blann, K., Dixon, J. T., Hess, F. M., Killian, E., Maumela, H., McGuinness, D. S., Morgan, D. H.,
Neveling, A., Otto, S., Overett, M. J., Slawin, A. M. Z., Wasserscheid, P., Kuhlmann, S. J. Am. Chem. Soc., 2004,
126,14712.
[3] Blann, K., Bollmann, A., Dixon, J.T., Hess, F.M., Killian, E., Maumela, H., Morgan, D.H., Neveling, A., Otto,
S.,Overett, M.J. Chem Comm, 2005, 620.
[4] Blann, K., Bollmann, A., Dixon, J.T., Hess, F.M., Killian, E., Maumela, H., Morgan, D.H., Neveling, A., Otto,
S.,Overett, M.J. Chem Comm, 2005, 622.
329
and/or

O-94
AN EFFICIENT CATALYTIC ASYMMETRIC SYNTHESIS AND BIOLOGICAL
EVALUATION OF α-SUBSTITUTED AROYLOXYL PHOSPHONATES
Hui Liu, Hongwu He and Wen-Jing Xiao*
Key Laboratory of Pesticide and Chemical Biology, Ministry of Education, College of Chemistry, Central China Normal
University, 152 Luoyu Road, Wuhan, Hubei 430079, China. E-mail: wxiao@mail.ccnu.edu.cn
We have synthesized a series of optically active phenoxylacetyloxyl and aroyloxyl phosphonates
in high enantiomeric purity via catalytic asymmetric hydrogenation using Rh(I)/(S,S)-Me-DuPHOS
as the catalytic system in methanol. Most of the target compounds including their precursors are
novel. The methodology described herein presents one of the most straightforward synthetic way to
get these compounds. The biological study shows that aroyloxyl phosphonates with R-configuration
possess excellent herbicidal activities against dicotyledons and can be used as potential herbicides.
O
MeO P
MeO
O
O
O
Cl
Cl
Rh(I)/(S,S)-Me-DuPHOS
MeOH, S/C=100,
H 2 (4 atm), 15 o C, 12 h
330
O
MeO P
MeO
O
References
[1] Horiguchi, M.; Kandatsu, M. Nature 1959, 184, 901.
[2] (a) Allen, M. C.; Fuhrer, W.; Tuck, B.; Wade, R.; Wood, J. M. J. Med. Chem. 1989, 32, 1652. (b) Smith, W. W.;
Bartlett, P. A. J. Am. Chem. Soc. 1998, 120, 4610.
[3] (a) He, H.-W.; Liu, Z.-J. Chin. J. Org. Chem. 2001, 21, 878. (b) Wang, T.; He, H.-W. Synth. Commun. 2004, 34, 1415.
(c) He, H.-W.; Liu, X.; Hu, L.; Wang, S.; Liu, Z. Phosphorus Sulfur Silicon, 2002, 177, 1651. (d) He, H.-W.; Wang, J.;
Liu, Z.-J. Chin. Chem. Lett. 1994, 5, 35. (e) He, H.-W.; Liu, X.; Hu, L. M.; Wang, S.; Liu, Z.-J. Phosphorus Sulfur Silicon
1999, 144, 633.
O
O
Cl
Cl

O-95
CONTROLLED SYNTHESIS OF ORGANIC-INORGANIC MATERIALS DERIVED FROM
PHOSPHOROUS COMPOUNDS. VARIABLE POROSITY, PHOTOINDUCED
ELECTRON-TRANSFER AND HYDROGEN STORAGE
Ernesto Brunet, Olga Juanes, Juan Carlos
Rodríguez-Ubis Department of Organic Chemistry, Faculty of Sciences Universidad Autónoma de Madrid,
28049-Madrid, Spain. E-mail: ernesto.brunet@uam.es
The preparation of solid structures is more and more in the side of designing and predictive
principles conceptually similar to those used in solution chemistry. [1] Provocative comments as
famous as that of Maddox [2] are being rebuked by the results of thoughtful experiments within the
rapidly maturing field of crystal engineering. [3] For example, the use of layered inorganic salts in
which organic structures can be orderly deposited either by weak interactions or covalent bonds is a
widespread technique to prepare tailored solids with coveted properties. [4] Zirconium phosphate [5]
(ZrP) is an excellent example. It constitutes a lamellar template which we profusely use [6] to obtain
a number of microcrystalline materials with outstanding properties, ranging from molecular
recognition, [7] luminescence, [8] postsynthesis variable porosity, [9] chiral memory, [10] hydrogen
storage [11] and electron transfer in the solid state. [12] In this communication past and recent results of
our investigations will be reported.
References
[1] A. Dey, M. T. Kirchner, V. R.Vangala, G. R. Desiraju, R. Mondal, J. A. K. Howard, J. Am. Chem.
Soc. 2005, 127, 10545.
[2] J. Maddox, Nature 1988, 335, 201
[3] P. Erk, H. Hengelsberg, M. F. Haddow, R. van Gelder, Cryst. Eng. Comm. 2004, 6, 474.
[4] D. B. Mitzi, Chem. Mater. 2001, 13, 3283.
331

[5] A. Clearfield, Z. K. Wang, J. Chem. Soc.,Dalton Trans., 2002, 2937.
[6] E. Brunet, M. J. de la Mata, H. M. H. Alhendawi, C. Cerro, M. Alonso, O. Juanes, J. C. Rodriguez-
Ubis, Chem. Mater. 2005, 17, 1424.
[7] E. Brunet, M. Huelva, R. Vázquez, O. Juanes, J.C. Rodríguez-Ubis, Chem. Eur. J. 1996, 12, 1578.
[8] E. Brunet, M. J. de la Mata, O. Juanes, J. C. Rodriguez-Ubis, Chem. Mater. 2004, 16, 1517.
[9] E. Brunet, M. J. de la Mata, O. Juanes, J. C. Rodriguez-Ubis, Angew. Chem., Int. Ed. 2004, 43, 619.
[10] E. Brunet, Chirality 2002, 14, 135.
[11] E. Brunet, H. M. H. Alhendawi, C. Cerro, M. J. de la Mata, O. Juanes, J. C. Rodríguez-Ubis,
Angew. Chem. Int. Ed. 2006, 45, 6918.
[12] E. Brunet, M. Alonso, M. J. de la Mata, S. Fernandez, O. Juanes, O. Chavanes, J. C. Rodriguez-
Ubis, Chem. Mater. 2003, 15, 1232
332

O-108
STUDY ON THE PREPARATION OF WHEAT STARCH PHOSPHATE WITH LOW
DEGREE OF SUBSTITUTION
Liu Zhongdong*, Yang Yan
Henan University of Technology, ZhengZhou South Songshan Road 140#, 450052
liuzhongdong2345@163.com
The starch phosphate is one kind of modified starch products, which is also a kind of anionic
starch. Compared to the original ones, the aleurone of starch phosphate is not liable to the
degradation of bacteria, having a higher viscosity, transparency and glueyness. In the food
processing, the starch phosphate is used as the emulsifier, thickener or stabilizer. For its well
stability of freezing-melting, the starch phosphate is especially suitable to be applied in the frozen
foods. The starch phosphate is used for the paper sizing in the paper manufacturing industry and in
the textile industry, it is used for the fabric sizing, dressing, printing and dying, both of which has a
better result than the original starch. In addition, the starch phosphate can be used as adhesive,
sedimentation agent, drug bulking agent and detergent etc.
By means of proper experimental design, the method of response surface is applied to fit the
function relationship between factors and response value using multiple quadratic regression
equations and to find out the best technological parameter to solve the multivariate problem by the
analysis of the regression equations. At the present time, it is one of the most effective methods in
the synthetic technique of chemistry industry.
In order to improve the performance of wheat starch and to broaden its using range, the response
surface analysis is used in this article to optimize the response condition of the starch phosphate,
using the sodium pyrophosphate as catalyst in esterification to prepare the wheat starch phosphate,
to explore the influence of the pH, temperature, operation time and the amount of phosphate to the
viscosity characteristic of the products. The best technological conditions are determined by means
of response surface design, and the perfect result is obtained after the nature research of all the
products. Compared to the original ones, the wheat starch phosphate products which are prepared
through the response surface analysis has a satisfied value of the water retentiveness, the thickening
strength and the freeze-thawing stability, while its gelatinization temperature has a great reduction.
This research serves as reference to find out how to raise the economic benefits of wheat further
processing and how to handle its bulk by-products especially for China, the most important wheat
producing area.
333

P-8
STRUCTURAL CHARACTERISTIC AND ELECTRODE ACTIVITIES OF
PHOSPHORUS INCORPORATED TETRAHEDRAL AMORPHOUS CARBON FILMS
Aiping Liu, Jiaqi Zhu, Jiecai Han, Huaping Wu
Center for Composite Materials, Harbin Institute of Technology, Harbin 150080, China
The conductive phosphorus incorporated tetrahedral amorphous carbon (ta-C:P) films were
deposited on conductive p type Si wafers by filtered cathodic vacuum arc (FCVA) technology with
phosphine (PH3) as the dopant source. The structural characteristics were investigated by X-ray
photoelectron spectroscopy (XPS), Raman spectroscopy and Fourier transform infrared (FTIR)
spectroscopy. The electrochemical behaviors of ta-C:P films as electrodes were examined by cyclic
voltammetry (CV) and differential pulse voltammetry (DPV). The results showed that the inorganic
films represented amorphous structure with high tetrahedral bonds by Raman spectra. XPS data
indicated that the fraction of sp2-hybridized carbon atoms increased with PH3 incorporated, which
contributed to the improvement of conductivity. There was a possibility of carbon and phosphorus
bonds inferred from the activated vibrational bands detected from the IR spectra. The ta-C:P films
as electrodes exhibited excellent electrochemical activity compared with boron doped diamond
(BDD) electrodes, including a large electrochemical potential window, a low background current
and a considerable electrochemical activity toward ferricyanide reduction and metal ion analysis.
These characteristics demonstrated greatly potential application of the ta-C:P film electrodes for
electrochemical analysis and waste water treatment.
334

P-12
ELECTRON CONDUCTING MATERIALS ON THE BASIS OF
PERFLUOROPHENYLENE-PHOSPHANES
Berthold Hoge, Sonja Hettel, Nina Rehmann
Klaus Meerholz Universität zu Köln, Greinstr. 6, 50939 Köln, Germany. E-mail: b.hoge@uni-koeln.de
Organic semiconducting materials are of great interest with respect to their applications as
organic light-emitting diodes (OLEDs), organic field-effect transistors (OFETs) and photovoltaic
cells. Compared to the p-type semiconductors such as pentacene, electron-transporting (n-type)
semiconductors are still not fully developed and the performances are not satisfactory. Recently,
high performance n-type semiconductors have been obtained by modifying known p-type cores like
acene and oligothiophene derivatives with strongly electron withdrawing fluoro/fluoroalkyl
substituents. However, the influence of fluorinated substituents on the injected electrons is not fully
understood, and has often been attributed to the reduction in LUMO energies.
Polyperfluorophenylenephosphane derivatives (PPFPPs), [P(R)C6F4]n, are accessible by
deprotonation of HP(R)C6F5, followed by oligomerization of the intermediary formed phosphanide
ions, P(R)C6F5-, or by the complex reaction sequence of bromo(pentafluorophenyl)phosphane
derivatives, Br-P(R)C6F5 with R = Ph, C6F5, and elemental magnesium.
Orienting measurements of the obtained materials in “electron only devices” give evidence for
PPFPPs being potential n-type semiconductors. Due to the inhomogenous composition of PPFPPs
and the incommoding magnesium salts, molecular perfluorophenylenephosphanes with four
phosphorus atoms such as P(C6F4PPh2)3 appear to be suitable to increase electron mobility and
lifetime of the resulting electronic devices which were prepared by spin coating techniques.
335

P-13
SYNTHESIS AND CYTOTOXIC EVALUATION OF NOVEL NAPHTHOQUINONE
FUSED PHOSPHORUS HETEROCYCLES
Bin Wang, a Zhiwei Miao, a You Huang a , Ruyu Chen a , and Jie Wang, b
aState Key Laboratory and Institute of Elemento-Organic Chemistry, Nankai University, Tianjin 300071, China
bTianjin Institute of Medical and Pharmaceutical Sciences, Tianjin 300020, China.* Tel:+86 22 23508857; fax: +86 22
23503627; E-mail: chenry@syn.nankai.edu.cn
A series of novel naphthoquinone fused cyclic α-aminophosphonates, 2-alkoxy-3,4-dihydro-
2H-naphtho[2,3-e][1,4,2]oxazaphosphinane-5,10-dione 2-oxide 3-44 have been synthesized for the
first time. X-ray crystallography was performed on compound 14 in order to determine the exact
stereoisomer. The new P-heterocyclic quinone compounds have been evaluated for antitumor
activity on four human tumor cell lines, and five of them possessed significant cytotoxicity (IC50:
0.019–7.64 μM) comparable to that of the reference drug doxorubicin. The molecule size of
compound 3 indicated that these quinone-phosphorus heterocycles may be DNA-intercalators.
©2000 Elsevier Science Ltd. All rights reserved.
Acknowledgments:
This work was supported by Nankai University (J02044 to Zhiwei Miao). We are grateful to Dr.
Liangnian He for his encouragement throughout this work.
Reference and Notes
[1] Middleton, R. W.; Parrick J., In The Chemistry of the Quinonoid Compounds, By Patai, S., Rappoport, Z., Eds.;
John Wiley & Sons: London, 1988; Vol. 2, pp 1019–1066.
[2] Deny, W. A. Anti-Cancer Drug. Des. 1989, 4, 241.
[3] Kohn, K. W. Cancer Res. 1996, 56, 5533.
[4] Yoo, H. W.; Suh, M. E.; Park, S. W. J. Med. Chem. 1998, 41, 4716.
[5] Park, H. J.; Kim, Y. S.; Kim, J. S.; Lee, E. J.; Yi, Y. J.; Hwang, H. J.; Suh, M. E.; Ryu, C. K.; Lee, S. K. Bioorg. Med.
Chem. Lett. 2004, 14, 3385.
[6] Bolognese, A.; Correale, G.; Manfra, M.; Lavecchia, A.; Mazzoni, O.; Novellino, E.; Colla, P. L.; Sanna, G.; Loddo,
R. J. Med. Chem. 2004, 47, 849.
[7] Ryu, C. K.; Han, J. Y.; Jung, O. J.; Lee, S. K.; Lee, J. Y.; Jeong, S. H. Bioorg. Med. Chem. Lett. 2005, 15, 679.
[8] Gomez-Monterrey, I.; Santelli, G.; Campiglia, P.; Califano, D.; Falasconi, F.; Pisano, C.; Vesci, L.; Lama, T.; Grieco,
P.; Novellino, E. J. Med. Chem. 2005, 48, 1152.
[9] Garuti, L.; Roberti, M.; Pession, A.; Leoncini, E.; Hrelia, S. Bioorg. Med. Chem. Lett. 2001, 11, 3147.
[10] Kafarski, P.; Lejczak, B. Curr. Med. Chem.-Anti-Cancer Agents. 2001, 1, 301.
[11] Faulkner, D. J. Nat Prod. Rep. 2002, 19, 1.
[12] Bittner, S.; Gorohovsky, S.; Paz-Tal, O.; Becker, J. Y. Amino Acids, 2002, 22, 71.
[13] Kafarski, P.; Lejczak. B. In Aminophosphonic and Aminophosphinic Acids. Chemistry and Biological Activity,
Kukhar V. P., Hudson H. R. Eds.; John Wiley & Sons: Chichester: 2000, pp 37-38.
[14] Zhou, J.; Qiu, Y. G.; Feng, K. S.; Chen, R. Y. Synthesis 1999, 1, 40.
[15] Wang, B.; Miao, Z. W.; Huang, Y.; Chen, R. Y. Heteroatom Chem. In press.
[16]Wang, B.; Chen, R. Y.; Huang, Y.; Miao, Z. W. Chinese. J. Struct. Chem. 2006, 25, 523.
[17] Podrebarac, E. G.; Cheng, C. C. J. Org. Chem. 1970, 35, 281.
[18] Crystallographic data were deposited at Cambridge Crystallographic data Center, 12 Union Road, Cambridge CB2
1EZ, UK and are available free from there under the deposition number CCDC 294861 for cis-14 and 609760 for 3.
336

[19] Maury, C.; Gharbaoui, T.; Royer, J.; Husson, H. P. J. Org. Chem. 1996, 61, 3687.
[20] Dimukhametov, M. N.; Bayandina, E. V.; Davydova, E. Y.; Zyablikova, T. A.; Dobrynin, A. B.; Litvinov, I. A.;
Alfonson, V. A. Russ. Chem. Bull. Int. Ed. 2001, 50, 2468.
[21] Skehan, P.; Storeng, R.; Scudiero, D.; Monko, A.; McMahon, J.; Vistica, D.; Warren, J. T.; Bokesch, H.; Kenney, S.;
Boyd, M. R. J. Natl. Cancer. Inst. 1990, 82, 1107.
[22] Gewirtz, D. A. Biochem. Pharmacol. 1999, 57, 727.
[23] Moore, M. H.; Hunter, W. H.; Kennard, O. J. J. Mol. Biol. 1987, 206, 693.
[24] Pindur, U.; Haber, M.; Sattler, K. J. Chem. Educ. 1993, 70, 263.
[25] Martin, D. R.; Pizzolato, P. J. J. Am. Chem. Soc. 1950, 72, 4584.
337

P-16
1,3,4-OXAZODIZAOLE CONTAINING CYCLO- AND POLYPHOSPHAZENE
Chen Zhao, Rui Bao, Jin-jun Qiu, Cheng-mei Liu*
Department of chemistry,Huazhong University of Science and Technology, Wuhan, 430074, P. R. China
Polyphosphazenes possess an inorganic P, N backbone with two organic groups connected to
each phosphorus atom. The properties of polyphosphazenes are largely controlled by the choice of
side groups. Polyphosphazenes that are hydrophobic, hydrophilic, ionic conductive, electro-
luminescent can be synthesized by careful choice of the side groups[1-5].
The electron–withdrawing character of the 1,3,4-oxadiazole ring in derivatives facilitates electron
injecting and transport. Polymers containing oxadiazole moieties in either the main chain or a side
group have been synthesized and their electron transportation properties have also been studied
[6-10]. The cyclotriphosphazene and polyphosphazene with oxadiazole group were synthesized in
this paper. The chemical structures are as follow:
O
N
N
N
N
O
O O
P
N N
O O
P P
N
O O
O N
N
CP
N N
O
O
N N
O
N
N
338
( N P ) ( N P )
a
b n
O O
N C
O
N
C
The chemical structures of CP and PP containing 1,3,4-oxadiazole ring were characterized by
FT-IR and 1H-NMR. The optical properties of CP and PP were characterized by UV-Vis and
fluorescent spectrum. The thermal properties were analyzed by DSC and TGA. The results
indicated that the UV-Vis absorption peak of CP was at 286nm(CHCl3 as solvent). When excited at
286nm, the emission peak was at 356nm. Weight loss of CP was only 1.02% on heating to 350 ℃
under nitrogen atmosphere.
The number average molecular weight of polymer was 1.03×104, the polydispersity index was
1.30 and Tg is 85 ℃ . The UV-Vis
absorption peak of PP was at 284nm(CHCl3 as solvent). When
excited at 283nm, the emission peak was at 360nm. Weight loss was 6.69% on heating to 350 ℃
under nitrogen atmosphere. The CP and PP containing 1,3,4-oxadiazole ring are potential
electroluminescence materials.
PP
OCH 3
References
[1] Allcock, H. R., Krause, W.E.. Macromol., 1997, 30, 5683-5687.
[2] Allcock, H. R., Rutt, J. S., Fitzpatrick, R. J. Chem.Mater..1991, 3, 442-449.
[3] Allcock, H. R., Fitzpatrick, R. J., Visscher, K. B.. Chem.Mater..1992, 4, 775-780
[4] Allcock, H. R., Visscher, K. B.. Chem. Mater..1992, 4, 1182-1187
[5] Louis M. Leung, C. M. Liu, C. K. Wong, et al. Polymer., 2002, 43, 233-237.
[6] Tzanetos, N. P., Kallitsis, J. K. Chem. Mater..2004, 16, 2648-2655.
[7] Jin, S.-H., Kim, M.-Y., Kim, J. Y., Lee, K.. J.Am.Chem.Soc..2004, 126, 2474-2480.
[8] Shu, C.-F., Dodda, R., Wu, F.-I. Macro-molecules.2003, 36, 6698-6703.
[9] Wu, F.-I., Shih, P.-I., Shu, C.-F., Tung, Y. Macromolecules.2005, 38, 9028-9036.
[10] Thomas, K. R. J., Lin, J. T., Tao, Y.-T.. Chem.Mater..2002, 14, 3852-3859.

P-19
STEREOSELECTIVE SYNTHESIS AND BIOLOGICAL ACTIVITIES OF
O-(E)-1-{1-[(6-CHLOROPYRIDIN-3-YL)METHYL]-5-METHYL-1H-1, 2,
3-TRIAZOL-4-YL}ETHYLENEAMINO O-ETHYL O-ARYL PHOSPHOROTHIOATES
De-qing Shi
Key Laboratory of Pesticide and Chemical Biology of Ministry of Education, Central China Normal University, Wuhan
430079, Hubei, P. R. China
Email: chshidq@yahoo.com.cn
Neonicotinoid insecticides,as nicotinic acetylcholine receptor inhibitors have attracted increasing
attention because of their safety, low toxicity and high activities [1, 2]. 1,2,3-triazole,
thiophosphorate oxime ethers and their derivatives have been used as insecticides, nematocides,
acaricides and plant growth regulators [3]. As a continuation of our research work in an attempt to
find high activity and low toxicity pesticidal lead compounds [4], we designed and synthesized a
type of novel phosphorothioates containing pyridine and triazole rings (See Fig. 1). Structures of the
products were characterized by IR, 1H NMR, 31P NMR, MS and elemental analyses, one of their
strucyures were determined by single crystal X-ray diffraction. Results of the preliminary bioassay
indicate that the title compounds possess potential insecticidal activities to some extent.
Cl
N
CH3 N
N
N
CH3 N
O
EtO P S
OAr
Ar=2,4-Cl 2C 6H 3 (a), 4-ClC 6H 4 (b), C 6H 5 (c),
2-CH 3C 6H 4 (d), 3-CF 3C 6H 4 (e), 3-CH 3C 6H 4 (f),
2-Cl,4-FC 6H 3 (g), 2-CH 3OC 6H 4 (h), 2,3-Me 2C 6H 3 (i)
Fig. 1
References
[1] (a) Shiokawa, K.; Tsubo, S.; Kagabu, S.; Moriya, K. EP Patent,192060 (1986); (b) Rudolf, E.; Ludwig, P. DE Patent,
2918775 (1980).
[2] Yamamoto, I.; Yabita, G.; Tomizawa, M. & Hissasomi, A. J. Pesti. Sci. 1994, 19, 335-339.
[3] Krivopalov, V . P.; Shkurko, O. P. Russian Chemical Reviews, 2005, 74 (4), 339-379.
[4] Luo, Z.-G.; Shi, D.-Q. J Heterocycl Chem 2006, 43, 1021-1026.
339

P-27
THE INFLUENTIAL FACTOR OF TEMPERATURE ON SYNTHESIS OF L-ARGININE
OLIGO-PEPTIDES MEDIATED BY PHOSPHORUS OXYCHLORIDE
Haiping Ren , Li Ma , Kui Lu*
School of Chemistry and Chemical Engineering, Henan University of Technology, Zhengzhou 450052 , China
The self-assembling into peptides for amino acids mediated by inorganic phosphorus has
become a focus of science research [1] , whose courses are investigated by using electrosprary
ionization mass spectrometry [2] .
In this paper, it was investigated that the reaction of influential factor of temperature on
synthesis of L-arginine oligo-peptides mediated by phosphorus oxychloride, quenching with water,
the reaction mixtures yielded the corresponding peptides. The ESI-MS showed that at 30 ℃ the
relative intensity of dipeptide(m/z=331)equal to the 35% of amino acid .When the temperature
improved to 40℃, in the same reaction time, the relative intensity of oligo-peptides mixtures could
not get more velocity as well as at 50 ℃ and even higher temperature. So improved the temperature
had a little effect on this reaction .
Figure The influential factor of temperature on synthesis of L-arginine Oligo-peptides ESI-MS
Acknowledgements: The authors would like to thank the financial supports from the Chinese
National Science Foundation (No.20272055, 20572016), Henan Province Science Foundation for
Prominent Youth (No.0312000900) and Office of Education of Henan Province (No.
2006KYCX017).
References:
[1] Lu, K.; Liu, Y.; Zhou, N.; Chen, Y.; Feng, Y.-P. ; Guo, X.-F.; Chen, W.; Qu, L.-B.; Zhao, Y.-F. Acta Chim. Sinica
2002, 60, 372 (in Chinese).
[2] Ba,J-F; Lu Z-Q; Liu N; Liu S-Y; Ji Z-J; Shen S-L. The ESI-MS investigation on synthesis of
poly-peptides.Analytical Chemistry,2005,33(5),661~664. (in Chinese)
340

P-28
DISTRIBUTION AND CONCENTRATION OF TOTAL NITROGEN, TOTAL
PHOSPHOROUS AND TOTAL ORGANIC CARBON IN SOUTH SEA, CHINA
Haiyan Wang 1 , Daxiong Han 2 ,Jianyun Lin 1 .
1 2
Third Institute of Oceanography, State oceanic Administration, Xiamen, 361005, China; Department of Pharmacy,
Medical College of Xiamen University, Xiamen 361005, China
Background: The marine biogeochemistries of carbon, nitrogen and phosphorous have come
under increased scrutiny because of their close involvement in climate change and coastal
eutrophication. However, to our knowledge, few data are available for total nitrogen (TN), total
phosphorous (TP) and total organic carbon (TOC) in South Sea, China.
Objectives: The present study aims to contribute to the knowledge of their status through
investigating the level and distribution of TN ,TP and TOC in South Sea, China.
Methods: A total of 108 seawater samples of 11 sites in south sea, china were collected during
August 29- September4. An automated and simultaneous method for determination of TN and TOC
was applied to all seawater samples. The combined system allowed simultaneous determination for
TOC and TN in the same sample using a single injection and provided low detection limits and
excellent linear ranges for both TOC and TN. The risk of contamination has been remarkably
reduced due to the minimal sample manipulation and automated analyses. And quantitative analyses
of TP in seawater were accomplished by a typical chemical method.
Results: Concentration ranges of TN and TP were 0.06-0.67, and 0.003-0.071 mg/L, respectively,
as well as that of TOC were 0.23-2.51mg/L. The values of TN and TP showed that the status of
nutrition is relatively better in south sea than other marine areas. Moreover, the upright change trend
of TN concentration level as well as TP and TOC according to the experimental results at the total
11 sites is shown in figure 1. The concentration of TN initial increases with the increasing of the
depth, later the value becomes almost constant.
In contrast, the concentration of TOC reduces with the increasing of the depth, later the value
becomes almost unchangeable. Compared with the trend of TN and TOC, that of TP appears
relatively stable. Thus, TP could be regarded as the key factor about eutrophication. This work
should provide some useful information to better understand the environmental status of south sea
in china.
mg /L
2
0
D-06
0 200 400 600 800 1000 1200 1400 1600
341
TOC
TN
TP
Figure 1 the uprigit change trend of TN, TP and TOC in south sea, china,
take site D-06 as an example
m

P-29
MOLECULAR DOCKING OF SUBSTITUTED ALKYLPHOSPHONATES TO
PYRUVATE DEHYDROGENASE
Hao Peng, Hong-Wu He*
Key Laboratory of Pesticide and Chemical Biology, Ministry of Education; and College of Chemistry, Central China
Normal University, Wuhan 430079, China. *E-mail: he1208@mail.ccnu.edu.cn
Pyruvate dehydrogenases, which is known as a target of pesticides, catalyzes the first step of the
multistep process, using ThDP and Mg 2+ as cofactors. A series of acetylphosphinates or
phosphonates have been designed and synthesized as potent inhibitors of PDHc, but none of them
were active enough to be commercialized. 1 We began a systematic, long-term study aiming to
design new inhibitors of PDHc with phosphonate moiety as potential agrochemicals. A series of
1-(substituted phenoxyacetoxy)alkylphosphonate derivatives (Scheme 1) were synthesized and
showed notable herbicidal activities, and some of them have been demonstrated as inhibitors of
PDHc. 2-3
Fortunately, the X-ray structure of PDHc E1-ThDP-Mg 2+ has recently been determined, which
provided not only insights into the probable interaction mechanism of the PDHc E1 with the
inhibitors, but also valuable clues for the prediction of active sites. 4 To explore the inhibitory
mechanism, molecular docking studies on these analogues were performed. The Lamarckian
Genetic Algorithm (LGA) was applied to locate the binding orientations and conformations of the
1-(substituted phenoxyacetoxy)alkylphosphonate derivatives with the PDHc E1. A good correlation
between the calculated binding free energies and the experimental inhibitory activities suggests that
the identified binding conformations of these potential inhibitors are reliable. Therefore, the binding
model and the information of the inhibitor-enzyme interaction would be useful in developing new
agrochemical leads against the PDHc E1. Actually, Virtual screen was performed by using this
reliable model, and several new compounds with comparable activities were designed and
synthesized.
R
P
1O O
R2O O O
R 3
O
SCHEME 1
Acknowledgments
Financial support by National Basic Research Program of China (2003CB114400) and NNSFof
China ( 20372023)
References
[1] Baillie, A. C.; Wright, K.; Wright, B. J.; Earnshaw, C. G. Pestic. Biochem. Physiol., 30, 103 (1988).
[2] He, H. W.; Wang, T.; Yuan J. L. J. Organomet. Chem., 690, 2608 (2005).
[3] Tan, H. L.; Yuan, J. L.; He, H. W. Wang T. Chin. J. Chem. Engi., 6, 4 (2005).
[4] Arjunan, P.; Nemeria, N.; Brunskill, A.; Chandrasekhar, K.; Sax, M.; Yan, Y.; Jordan, F.; Guest, J. R.; Furey, W.
Biochemistry, 41, 5213 (2002).
342
X
Y

P-32
A PRACTICAL ROUTE TO SYNTHESIS SOME PHOSPHORYLATED PRODRUG
Hong-bo Zhang a , Ren-Zhong Qiao a,b *, Yufen Zhao b *
a Department of Pharmaceutical Engineering, Beijing University of Chemical Technology, Beijing 100029, China.;
b The Key Laboratory of Bio-organic Phosphorus Chemistry and Chemical Biology, Ministry of Education.
Nucleoside analogs have drawn a considerable attention as anti-HIV reagents. However, it is
found that d4T, AZT and other nucleoside analogs do not exert antiviral activity directly after
penetrating cells through a passive process, but can be phosphorylated to the corresponding mono-,
di- and triphosphates by cellular kinases to terminate the viral DNA elongation through strong
inhibition of HIV-RT elongation resulting in strong inhibition of HIV-RT. Thus, great efforts have
been continuously made to develop analogs of d4T and AZT. [1]
Here we introduce a route to establish a universal route to modify the structures of nucleoside
analogs by introducing a certain group with anti-HIV or anti-tumors activities. [2] In this route,
phosphorus trichloride is used as the phosphorylation agent, an asymmetric compounds were
synthesized by adding corresponding alcohols. A cold atmosphere is required to make sure the
reaction successfully.
Take d4T as an example, compound 1 is phosphorylated to give an asymmetry H-phosphonate
compound (Fig.1). Choline chloride and some kinds of steroids are phosphorylated with
considerable yields followed the route described above. [3]
HO
O
1
O
N
NH
O
i,ii
i. PCl3, CH2Cl2;
ii. iso-propyl alcohol, TEA.
Project supported by the National Natural Science Foundation of China (No. 20572008).
References
[1] Xu Tang, Cheng Huang, Hua Fu and Yu-fen Zhao, Synlett 2005, 12, 1930-1932.
[2] Xiao-Bin Sun, Jian-Xun Kang and Yu-Fen Zhao, Chem. Commun., 2002, 2414-2415.
[3] Rong Zeng, Hua Fu, Yu-fen Zhao, Macromolecular Rapid Communications, 2006, 27, 548–552.
343
O
O
P
H
2
O
O
NH
N
O
O

P-53
ULTRASONIC PHOTOCATALYTIC DEGRADATION OF THE PESTICIDE
“METHYL PARATHION”
LI He-ping*
Department of Chemistry and Environmental Engineering, Changsha University of Science and Technology, Changsha
410076, PR China Tel.: +86 731 2618234; Fax: +86 731 2618234; E-mail: lihepinghn@163.com
Different affecting factors on ultrasonic photocatalytic degradation of methyl parathion pesticide,
a kind of typical organophosphate insecticides, by adopting nano Fe3O4 doping anatase TiO2
catalyst after treatment of high-temperature activation was investigated. Experimental results
indicated that Fe3O4 doping TiO2 catalyst greatly enhanced the ultrasonic degradation, and
confirmes that methyl parathion is slowly degraded by direct ultrasonic photolysis in the presence
of dissolve oxygen. Addition of nano Fe3O4 doping anatase TiO2 to the reaction system substantially
increases the initial rate of reaction and the overall conversion of methyl parathion, the ultrasonic
degradation kinetics of methyl parathion pesticide in the presence of nano anatase TiO2 catalyst
followed the first order reaction. The degradation ratio is 96.5% for methyl parathion pesticide,
99.0% removal for COD with in 60 min under the experimental conditions such as 40 K Hz
ultrasonic frequency, 5.0 W/cm2 output power, 500 mg/ L amount of TiO2 catalyst (1.5% doping),
pH 6.00, and temperature 25℃, when the initial methyl parathion pesticide concentration is 40
mg/L. Completely photocatalytic degradation of methyl parathion at pH = 6.00 was found to occur
in less than 90 minutes after reaction began.
344

P-56
APPLICATION OF TETRAKIS HYDROXYMETHYL PHOSPHONIUM
IN LEATHER PRODUCTION
Li Ya, Shao Shuangxi*, Jiang Lan, Han Ying, Shi Kaiqi
Institute of Applied Chemistry, Ningbo University of Technology, Ningbo 315016,Zhejiang, China. Tel: +86 574
87080148;Fax: +86 574 87081217; Email: nbssx@126.com
Tetrakis hydroxymethyl phosphonium salts hereafter are abbreviated as THP salts have been
widely used as textile retardants, oil-field waste water treatment agents and biocide in other fields.
In 1956, THP salts was firstly used in leather production. The use of THP salts in chrome free
tanning was studied in the following years and it was found that the copolymers of THP
chloride(THPC) and phenol can be used as pretannages to produce leathers having excellent
physical properties. The best tannages are obtained with a concentration of more than 3% THPC
and about 2% of phenol. THP salts can also be used as cross linkers in melamine formaldehyde or
urea formaldehyde solutions to form a copolymeric tanning agent in situ and the shrinking
temperature of the tanned leather is above 100 . The obtained leathers have ideal mechanical
℃
properties with the combination tanning of 8% THP salts and 8% dicyandiamine at pH 6.0. The
combination tanning of THP sulfate (THPS)-Fe, THPS-Al, THPS-silica, and THPS-silica-Al can
generate ideal leather with good organoleptic properties. The leather tanned by 2.5% Fe and 1.5%
THPS are light in colour and with the shrinkage temperature of about 95 and that of the leather
℃
tanned by THPS-silica-Al in combination is 86 . Furthermore, THP salts can be used in acid
℃
degreasing prior to tanning and as cross linker for casein finishes after tanning. But the mechanism
of THP salts tanning was poorly understood. The study indicates that THP salts mainly link with the
amino groups of hide collagen at a mole ratio of n(P):n(N)=1:2.2. The release of formaldehyde in
the process of THP salts tanning is one of the deterring factors for their widespread application in
leather tanneries.
345

P-58
THE SYNTHESIS OF
N-HYDROXYMETHYL-3-(DIALKYLPHOSPHONO) PROPIONAMIDE
Xiao-lian Hu 1 , Ru-yi Zou 1 , Shang-bin Zhong 1 , Jun-liang Yang 1 , Zhi-yu Ju 1 , Yong Ye* 1 , Xin-cheng Liao 1 , Yu-fen
Zhao* 1,2
1. Department of Chemistry, Key Laboratory of Chemical Biology and Organic Chemistry, Zhengzhou University,
Zhengzhou, 450052, China; 2. The Key laboratory for Bioorganic Phosphorus Chemistry and Chemical Biology
(Ministry of Education), Department of Chemistry, Tsinghua University, Beijing 100084,China. E-mail:
yeyong03@tsinghua.org.cn; yfzhao@mail.tsinghua.edu.cn.
It has been known for over 30 years that phosphorus compounds can retard flame in cellulosic
textiles. Despite being frequently implicated in fires causing injuries and fatalities, cotton fabrics
have a major share of the world’s textile market. Cotton is essentially cellulose and most durable
fire-retardancy finishing has been done by the application of organo phosphorus compounds. Being
rich in phosphorus and nitrogen, phosphonopropionamide (pyrovatex CP) has been successfully
used as a flame-retardant agent for cotton. In order to investigate effect of the N/P ratio, we
prepared some pyrovatex CP. Synthetic route is shown at follow:
Freshly-prepared sodiun alkyloxide solution was added slowly to a solution of acrylamide and
dialkyl phosphite. The reaction was monitored by ESI-MS. The propionamide was isolated by
seeding the cooled solution and filtering off the precipitated crystals. These were washed with
organic solvent and dried. The propionamide was then added gradually to formalin, the pH of the
mixture being maintained at 8.0 by adding approximately caustic soda solution. After the reaction
completed (detected by ESI-MS), it was allowed to cool to room temperature and filtered. A
solution of N-hydroxymethyl-3-(dialkylphosphono) propionamide was obtained. Its fire-retardancy
effect research is being continued.
Acknowledgments: the authors would like to thank the financial supports from NNSFC
(No.20602032 and 20572061
Reference
[1] R. B. Le Blanc , Text Ind. 1974, 138, 115
[2] R. Bruce, R. L. b. Le Blanc, Text Chem. Colorist, 1997, 29,2
[3] F .F. Flynn, W. A. Reeves, J. D. Futhrie, et al., US 2,743,299
[4] H. N. Dornach, H. H. Basel, J. Kern, et al., US 3,754,981
346

P-60
ELECTROSPRAY IONIZATION TANDEM MASS SPECTROMETRY OF
N-PHOSPHORYL-α-, β- AND γ- AMINO ACIDS
Liming Qiang a , Shuxia Cao a , Jianchen Zhang a , Xincheng Liao a , Yufen Zhao a,b *
a The Key Laboratory of Chemical Biology and Organic Chemistry, Department of Chemistry, Zhengzhou University,
Zhengzhou, 450052, P.R.China; b Key Laboratory for Bioorganic Phosphorus Chemistry of Ministry of Education,
Department of Chemistry School of Life Sciences and Engineering, Tsinghua University, Beijing 100084, P.R.China
Phosphoryl amino acids are the smallest units of phosphoproteins and have many interesting
biomimic reactivities1. It is significant to study them by electrospray ionization mass spectrometry
(ESI-MSn) for further understanding their unique structure.
In this letter, different kinds of N-phosphoryl amino acids, such as N-(O,O′-diisopropyl)
phospho-L-α-alanine (DIPP-L-α-Ala), N-(O,O′-diisopropyl) phospho-D-α-alanine (DIPP-D-α-Ala),
N-(O,O′-diisopropyl) phospho-β-alanine (DIPP-β-Ala) and N-(O,O′-diisopropyl) phospho-γ-amino
butyric acid (DIPP-γ-Aba) were investigated by positive and negative electrospray ionization ion
trap mass spectrometry (ESI-MS/MS). Their fragmentation pathways were investigated. The
stepwise fragmentation of [M+ Na]+ ions and [M- H]- ions of them all underwent a five-membered
(for DIPP-L-α-Ala and DIPP-D-α-Ala)2, six-membered (for DIPP-β-Ala) and even
seven-membered (for DIPP-γ-Aba) ring transition state formed by the nucleophilic attack of the
C-terminal carboxyl oxygen on the phosphorus (Figure 1), leading to a P–N to P–O bond migration.
The phenomenon could be as a result of the strong affinity of the phosphoryl group for the hydroxyl
group.
a b
(H 3C) 2HCO
HO
ONa
P
HO
H
N
O
(CH 2 )n
347
O
HO
P
N
O
(CH 2)n
[M+Na-C 3H 6] + [M-H-(CH 3) 2CHOH-C 3H 6] -
n=2: M=253 for DIPP-β-Ala; n=3: M=267 for DIPP-γ-Aba
FIGURE 1 Six-membered ring or seven-membered ring transition state for DIPP-β-Ala and
DIPP-γ-Aba: a. sodium adducts; b. negative ions
References
[1]. Cheng CM, Liu XH, Li YM, et al. Origins of Life and Evolution of the Biosphere. 2004, 34: 455.
[2]. Cao SX, Zhang JC, Xu J, Liao XC, Zhao YF. Rapid Commun. Mass Spectrom. 2003, 17: 2237.
O

P-63
SEDIMENT PHOSPHORUS BUFFERING CAPACITY IN DRAINAGE DITCH IN HILLY
AREA OF PURPLE SOIL, CHINA
Luo Zhuan-xi 1,2 ,Zhu Bo 1 ,Wang Tao 1,2
1, Institute of Mountain Hazards and Environment ,the Chinese Academy of Sciences , Chengdu 610041, China;
2, Graduate School of the CAS ,Beijing 100039, China
Phosphorus (P) losses from residence/agriculture lands degrade surface waters due to
anthropogenic eutrophication. A large portion (great than three-fourth) of the eroded sediment is
deposited in their delivering ways, such as stream and drainage ditch network. Stream and ditch
sediments interact with P in the water column and as such play a pivotal ecological role in buffering
in water column P concentration. Previous studies focused on plot-to-field scale P losses, ponds and
lakes sediment from sites interacting with soluble P and its risk evaluation. Little information
among different ditch types has been gathered on risk evaluations of sediment interacting with
water column P. This study was conducted to examine the phosphorus equilibrium between the
sediments and water column, sediment acting as whether or not potential impact on the
eutrophication of downstream in four different ditch types. Surface water and sediment samples
were collected and analyzed for organic matter (OM), pH, Conductivity, oxalate-extractable P,
oxalate-extractable Al and Fe content from sites along four ditches, i.e. Residence drainage ditch
(Rdd), Agriculture drainage ditch (Add), Single complex ditch (Scd, only one Rdd and Add together,
catchment area 32.4ha) and Multiple complex ditch (Mcd, many Rdd and Add together, catchment
area 1230ha).
Soluble P concentration was higher in source areas (Rdd (0.366mg P L-1), Add (0.143mg P L-1,
respectively) and greater catchments (Mcd, 0.123mg P L-1). However, the P concentration was one
time lower in smaller catchments than others (Scd, 0.067 mg PL-1). Most of Sediment from site in
ditch acted as P sink except Scd, which Soluble P in drainage water were greater than EPC0
concentrations. The phosphorus sorption maximum (Smax) ranged from 145.75 to 289.35 mg P
kg-1 sediment, which Smax in Rdd was lowest, but Smax in Add was greatest, and Smax between
Scd and Acd were not obviously different, i.e. 234.31, 210.32 mg P kg-1 sediment, respectively;
equilibrium P concentrations (EPC0) ranged from 0.03 to 0.06 mg P L-1, which Rdd > Add> Scd >
Mcd. Therefore, Add, Scd and Mcd had stronger p buffering capacity than Rdd, probably resulting
from the drainage polluted water because of higher soluble P in water column.
The degrees of phosphorus saturation (DPS) of ditch sediments were lower than critical value of
DPS (25%), ranged from 4.01 to 8.96%, which had not a potential impact on eutrophication of
receiving water. Smax was significantly correlated oxalate-extractable P (Pox, r2 =-0.997, p

P-83
LIQUID CRYSTALLINE BEHAVIOR OF CYCLOTRIPHOSPHAZENE
Rui Bao, Chen Zhao, Jin-jun Qiu, Cheng-mei Liu*
Deparment of Chemistry, Huazhong University of Science and Technology, Wuhan, 430074, P. R.China
A great deal of scientific and technological work has been devoted to supermolecular liquid
crystals in recent years[1,2]. Cyclotriphosphazenes are very attractive inetermidie in this area.
These compounds are highly versatile molecules with a multiarmed rigid ring that can be used as a
core for the formation of one-dimensional columnar superstructures. Recently,
cyclotriphosphazenes which exhibited columnar mesomorphism have been synthesized by Jimenez
J. et al.[3,4].
Cyclotriphosphazenes bearing stilbene derivatives as promesogenic units linked to phosphorus
atoms were synthesized in our group. The method was based on the direct reaction of
hexa(4-formylphenoxy)cyclotriphosphazene[N3P3(OC6H4-p-CHO)6] with six equivalents of
(4-alkoxyphenyl)acetonitrile[ROC6H4CH2CN](R=C2H5, C6H13, C12H25, C18H37).
OHC
OHC
OHC
O O
P
N N
O
P P
O
N
O
O
CHO
CHO
R=C2H5, C6H13, C12H25, C18H37
CHO
+
NC
OR
RO
349
O
O
P
N N
O
P P
O
N
O
O
The structures of the products were characterized by 1H-NMR, 31P-NMR, UV-Vis and IR
spectra. The liquid crystalline behaviors of organocyclotriphosphzenes which have different
terminal alkyl chain are investigated by differential scanning calorimetry(DSC), polarized optical
microscopy(POM), and X-ray diffraction(XRD).
Reference
[1] Donnio B., Barbera J., Gimenez R., et al. Macromolecules, 2002, 35, 370-381.
[2] Dimitrakopoulos C. D., Malenfant P. R. L. Adv. Mater. 2002, 14, 99.
[3]Barbera J., Bardaji M., Jimenez J., et al. J. Am. Chem. Soc., 2005, 127(25), 8994-9002.
[4] Barbera J., Jimenez J., Laguna A., et al. Chem. Mater., 2006, 18(23), 5437-5445.
RO
OR
CN
NC
CN
NC
CN
OR
NC
OR
OR

P-84
MONITORING INFLUENCE OF REACTION CONDITIONS ON SELF-ASSEMBLY INTO
OLIGO-PEPTIDES FOR THREE SULF-AMINO ACIDS BY USING ESI-MS
Kui Lu,Rui Li,Li Ma
School of Chemistry and Chemical Engineering, Henan University of Technology, Zhengzhou 450052, China
The amino acids and phosphorus play vital roles in life science. Even though there are lots of
papers about peptide synthesis related to the chemical evolution of life, there is litter investigation
on the intrinsic relationship between the phosphorus and amino acids [1] .
In our previous work, we found that with the assistance of inorganic phosphorus amino acids
could be assembled into oligo-peptides [2] . In this paper, the phosphorylation of three sulf-amino
acids and the self-assembly into oligo-peptides mediated by phosphorus oxychloride were studied
by using electrospray ionization mass spectrometry (ESI-MS). On quenching with water, the
reaction mixtures, which were produced under different reaction conditions, yielded the
corresponding peptides. Influence of the reaction conditions such as reaction time, solvent and
temperature on self-assembly into olig-peptides for three sulf-amino acids were monitored. Also,
the assembled into oligo-peptides activity of three sulf-amino acids were discussed. The reactions
are shown in scheme 1.
O
H 2N CH C
R
OH
POCl 3
R = H2C S S CH2 CH COOH
R = H2C CH2 S CH3 R =
H 2C SH
H 2O or ROH
NH 2
350
H
O
HN CH C OH
n
R
n = 2~4
n = 2~11
n = 2~9
Scheme 1 Self-assembly of three amino acids into oligo-peptides mediated by phosphorus
oxychloride
In conclusion, a simple and efficient method for the synthesis of oligopeptides have been found.
The presence of phosphorus could accelerate the interaction of amino acids. It might be useful in
the study about the origin of protein and co-evolution of life.
Acknowledgements: The authors would like to thank the financial supports from the Chinese
National Science Foundation (No.20272055, 20572016), Henan Province Science Foundation for
Prominent Youth (No.0312000900) and Office of Education of Henan Province (No.
2006KYCX017).
References:
[1] N. Zhou, K. Lu, Y. Liu, et al, The abstracts of the 13 th international conference on the origin of life, 2002, P87
[2] K. Lu, Y. Liu, N. Zhou, et al, Acta Chimica Sinica, 2002, 60(2): 372 (in Chinese)

P-90
ISOLATION AND DETERMINATION OF DIASTEREOISOMERS OF AMINO ACID
HYDRIDOPHORANE BY HPLC-ESI-MS
Shuxia Cao 1 , Yali Xie 1 , Jinming Liu 1 , Yanchun Guo 1 , Xincheng Liao 1, Yufen Zhao 1,2*
1 Key Laboratory of Chemical Biology and Organic Chemistry, Department of Chemistry, Zhengzhou University,
Zhengzhou, 450052, P.R.China ; 2 Key Laboratory for Bioorganic Phosphorus Chemistry of Ministry of Education,
Department of Chemistry School of Life Sciences and Engineering, Tsinghua University, Beijing 100084, P.R.China
Pentacoordinated phosphorus derivatives have biochemical activities and are widely used in
medicine, pesticide and ergonomics, etc. Hydridophorane is a kind of special pentacoordinated
phosphorus derivatives, and has versatile specific properties which can be used to synthesize some
important compounds.[1] The new literature reported that pentacoordinated bimolecular amino acid
hydridophorane could be a new kind of potent and efficient inhibitors towards tyrosinase.[2] So we
synthesized a series of pentacoordinated bimolecular amino acid hydridophorane and in the system,
a pair of diastereomers of hydridophorane were observed. In this letter, HPLC-ESI-MS was used to
isolate and determinate the diastereoisomers. L-valine was taken as an example. By the reaction of
L-valine, triethylamine and phosphorus trichloride in THF at 70 ℃ for two hours, bimolecular
L-valine hydridophosphorane were synthesized. The products were subjected to HPLC-ESI-MS. As
shown in figure1, the diastereoisomers were isolated and determinated. As shown in figure2, the
absolute configuration was determinated by the X-ray crystallographic study.[3] The peak1 in Fig1
was corresponding to a configuration, and the peak2 in Fig1 was corresponding to b configuration.
We have established an effective methodology for synthesizing and isolating hydridophorane, and
through this method, the diastereoisomers of L-Trp, L-Phe, L-leu, L-Met hydridophorane were
isolated and determinated. The results provide a better method for synthesizing and isolating a
certain configuration pentacoordinated bimolecular amino acid hydridophorane .
Fig. 1 HPLC chromatogram of the L-valine hydridophosphorane
Fig.2 Diastereomers configurations of L-valine hydridophosphorane
References
[1] Liu Lun-zu, Liu Zhao-jie. An Introduction to Organophosphorus Chemistry [M]. Wuhan: Central China Normal
University Press,1991, 182.
[2] Yu L, Liu Z, et al. [J], Amino Acids, 2005, 28: 369-372.
[3] Shu-Xia Cao,Jin-Ming Liu,et al. Acta Cryst, 2006, E62, 4642-4643.
351

P-97
SYNTHESIS OF LONG CHAIR ORGANOPHOSPHORUS COMPOUNDS ON THE BASIS
OF INDUSTRIAL FRACTIONS OF HIGHER OLEFINS
Il’yas S. Nizamov 1 , Yan Ye. Popovich 1 , Yevgeniy S. Ermolaev 1 , Il’nar D. Nizamov 1 , Gulnur G. Sergeenko 1 , Vladimir A.
Alfonsov 1 ,Elvira S. Batyeva 1 , Magdeev I.M. 1 , Reznik V.S. 1 , Sinyashin O.G. 1 , Yarullin R.S. 2
1 A.E. Arbuzov Institute of Organic and Physical Chemistry,Arbuzov Str., 8, Kazan, 420088, Russia, E-mail:
nizamov@iopc.knc.ru ; 2 Join Stock Company “Tatneftekhiminvest-holding”, Yershov Str., 29, Kazan, 420045, Russia,
Technological methods were developed for synthesis of higher phosphorus acids and thioacids,
their esters and salts by the reactions of phosphorylation and thiophosphorylation of olefins of
industrial fractions С16-С40 and propylene tetramer with phosphorylating agents. Thus, convenient
method of synthesizing O,O-dialkyl esters of long chair alkylphosphonic acids was developed by
the reactions of O,O-dialkyl phosphites with olefins of fractions С16-С18, С20-С26 и С28-С40 in
1:1 molar ratio in the presence of catalytic amounts of benzoyl peroxide at 135-140 оС for 10-12 h.
O,O-Dialkyl alkylphosphonates were isolated by vacuum distillation in 62-80 % yields.
O,O-Dialkyl alkylphosphonates were used as intermediates for the synthesis of corresponding
higher alkylphosphonic acids and their potassium salts.
CH
3
-(CH
2
)
n
-C(R')=C(R")H + (RO)
2
PH
R = Me, Pr-i; R' = H, Alk; R" = H, Alk; n = 13-37
O
352
CH 3 (CH 2 ) n C(R')H-С (R")H-P(OR) 2
Higher alkylphosphonous and dialkylphosphinic acids were obtained by the reactions of water
solution of hypophosphorous acid with olefins of fractions С16-С18, С20-С26 and С28-С40 and
propylene tetramer in 1:1 molar ratio in the presence of benzoyl peroxide (5 % mass.) and sulfuric
acid under refluxing.
O
O
H H
CH
3
-(CH
2
)
n
-C(R")=C(R')H
2
POH
CH
3
-(CH
2
)
n
-C(R")H-С(R')H-P
OH
O
R'= H, Alk; R" = H, Alk; n = 13-32
+ CH 3 (CH 2 ) n C(R")H-С(R')H-P-C(R')H-C(R")H-(CH 2 ) n CH 3
Addition reactions of dithiophosphoric and bisdithiophosphonic acids with olefins of fractions
С16-С18 and С20-С26 and propylene tetramer were performed at 80 о С for 1-2 h in 1:1 molar ratio
in the presence of anhydrous of ZnCl2 in acetonitrile solution with the formation of products formed
in accordance with Markovnikow’s rule.
S
S
ZnCl
2
(RO)
2
PSH + CH
3
(CH
2
)
n
C(R')=C(R")H CH
3
(CH
2
)
n
C(R')-S-P(OR)
MeCN
2
CH
2
(R")
R = Et, i-Bu; R' = H, Alk; R" = H, Alk; n = 13, 15 и 17-23
OH
+
O

P-107
SYNTHESIS AND BIOLOGICAL ACTIVITIES OF O,O-DIALKYL
1-((2-CHLOROTHIAZOL-5-YL OR 6-CHLOROPYRIDIN-3-YL) METHYL
-4-METHYL-1H-1, 2, 3-TRIAZOL-4-YL-5-CARBONYLOXY SUBSTITUTED
METHYL PHOSPHONATES
Xiao-Bao Chen & De-Qing Shi
Key Laboratory of Pesticide and Chemical Biology of Ministry of Education, Central China Normal University, Wuhan
430079,Hubei,P.R.China,
E-mail:chshidq@yahoo.com.cn
Neonicotinoids, accounting for 10-15% sales in worldwide insecticides, are increasingly used for
crop protection and animal health due to their high activities and safety, [1]. Because of their
structures and action mechanism similarities to those of nicotine, the agrochemicals which contain a
pyridine ring or a thiazole ring are called neonicotinoids. The 1,2,3-triazoles and
1-hydroxyalkylphosphonates, which are used as insecticides, nematocides, acaricides and plant
growth regulators, [2,3] play an important role in pesticide science. In an attempt to find high
activity and low toxicity pesticidal lead compounds [4], we continually designed and synthesized a
type of novel phosphonates 6. The synthetic routine is listed in Scheme 1.
DMSO/K2CO3 CH3COCH2COOEt NaOH/H2O R R N3 R
N
N
N
CH3 COOEt
N
N
N
CH3 OH
O
1 2 3
SOCl 2
R N
N N
CH 3
O
Cl
Et 3N/CHCl 3
HOCHPO(OR 2) 2
R 1
353
R N
N N
4 5a~i 6a~i
a: R= Cl CH2 ; b: R=
N
CH3 O
OR2
O P
OR2 O R1 Their structures were confirmed by IR, 1H NMR, 31P NMR, MS and elemental analyses, two of
them were determined by single crystal X-ray diffraction. The insecticidal activities test of title
compounds are on the way.
References
[1] Yamamoto, I., and Casida, J. E., Eds. Nicotinoid Insecticides and the Nicotinic Acetylcholine Receptor,
Springer-Verlag,Tokyo,1999.
[2] Ogura, T.; Numata, A.; Ueno, H.; Masuzawa, Y. WO PCT 039 106 (2000).
[3] He,H.-W.;Wang.T.;et al. CN Patent 1685825 (2005).
[4] Luo, Z.-G.; Shi, D.-Q. J Heterocycl Chem 2006, 43, 1021-1026.
Cl
N
S
CH 2

P-110
DETERMINATION OF ORGRANOPHOSPHOROUS PESTICIDES USING
PHOSPHOROUS IONIC LIQUID AS EXTRACTION AND LPME-HPLC
Xie Hongxue 1 He Lijun* 1 Wang Meimei 1 Wu Xiuling 2 Wu NaNa 1
1.Department of Chemistry and Chemical Engineering, Henan University of Technology, Zhengzhou, China, 450052;
2.Faculty of Materials Science and Chemical Engineering, China University of Geosciences, Wuhan, China,430074
A novel method for the determination of phorate, poxim, parathion and other
orgranophosphorous pesticides(OPPs) in water samples has been developed using phosphorous
ionic liquid-based liquid-phase microextraction(LPME) [1] coupled with high-performance liquid
chromatography(HPLC). The resulting procedure was shown to be a good alternative methodology
for the determination of selected orgranophosphorous pesticides(OPPs) in environmental samples.
It is proved that the methods are simple, fast, reproducible, effective and environmentally friend.
The procedure of liquid-phase Microextraction(LPME) is show in Fig.1. The optimized
extraction conditions has been described in the literature. [2] The analytes include phorate, poxim,
parathion, carbofuran, chlorpyrifos, omethoate, carbaryl. These analytes consist of
orgranphosphorous pesticides (OPPs), Organochlorine pesticides (OCPs) and carbamate pesticides.
We used ionic liquids and other organic solvent as extraction of liquid-phase Microextraction
(LPME). The result suggests that the extraction efficiency of phosphorous ionic liquid
(1-butyl-3-methylimidazolium hexafluorophosphate, [C4MIM]PF6) [3] is better than that of organic
solvent. Moreover, the enrichment folds of orgran phosphorous pesticides(OPPs) by phosphorous
ionic liquid([C4MIM]PF6) is especially high and steady. The phorate, poxim, parathion,
chlorpyrifos, omethoate and other phosphorous pesticides are greatly enriched by phosphorous ionic
liquid([C4MIM]PF6),and the enrichment factor of these are 665, 553, 630, 150 and 110,
respectively. The R.S.D. values obtained were satisfactory and ranged between 2.1% and 12.0% for
all analytes. The results show a interesting phenomena that the analytes and extraction solvent are
all phosphorous, which accords the similar dissolve mutually theory.
We synthesized phosphorous ionic liquids , including 1-butyl-3-methylimidazolium
hexafluorophosphate, 1-ethyl-3-methylimiazolium hexafluorophosphate,1-acetyl-3-methylimidazolium
hexafluorophosphate,1-butyl-3-methylimidazolium hexafluorophosphate, and so on. The
result show that these phosphorous ionic liquids can extract phosphorous pesticides efficiently. By
using this strategy, we synthesized especial ionic liquids, which may link with boracic, nickelic,
chloric and nitric group to extract boric, nickelic, chloricand nitric compound.
References
[1] Jeannot M A, Cantwell F F. Anal. Chem.[J], 1996 , 68: 2236
[2] Xie H X, He L J,Wu Y, Lu K,Si X Zh. China Anal. Chem[J],accept
[3]He L J, Zhang W Z, Zhao L, Liu X, Jiang S X. J. Chromatog. A.[J], 2003, 1007: 39.
354

Norm.
500
400
300
200
100
0
Fig.1 Schematic illustration of LPME system
1.Syringe 2. Aqueous sample
3. Water bath 4. Stirring bar
5. Magnetic stirrer 6. Syringe needle
7. PTFE ring 8. Extraction solvent
3.670
0 2 4 6 8 10 12
Fig.2 chromatogram of phorate in aqueous solution(a) and extracted by [C4MIM]PF6 (b)
(1= [C4MIM]PF6 2=water 3=phorate)
355
10.070
min

P-111
SYNTHESIS AND THERMAL PROPERTY OF
BIS(1-OXO-2,6,7-TRIOXO-1-PHOSPHABICYCLO[2,2,2]OCTANE-4-METHANOIC)-2,2-D
IMETHYL-1,3-PROPANEDIESTER
Xi-Jun Sheng, Zheng-Qiu Li, Hong-Wu He*
Key Laboratory of Pesticide and Chemical Biology of Ministry of Education, College of Chemistry, Central China
Normal University, Wuhan 430079, People's Republic of China.
Organophosphorus-containing flame retardant is a predominant product. It can give a charring
layer to coating the interface of the polymer during combustion. And this charring layer could serve
as a diffusion barrier to slow down the gasification and vaporization of organic polymers. As an
additive flame retardant, so many of them are liquid, and have a poor thermal property, evaporate
easily and do some bad to material’s property, these defects restrict the rang of their applications.
Compound PFR-8 which has a big molecular weight; good thermal stability and halogen free, was
designed and synthesized.
O
P
O
O HOCH2C(CH3) 2CH2OH O
O COCl
P
Et3N/CH3CN O
O
O
O
O
O
O O O P O
CH3 O
1 PFR-8
Scheme 1
Compound 1 was prepared from pentaerythitol (PE) and phosphorus oxychloride (POCl3)
according to literature. Compound PFR-8 can be obtained by the reaction of compound 1 with
neopentyl glycol (NPG) in the presence of triethylamine and acetonitrile, PFR-8 was obtained as
white solid in yield 86%. Its structure was confirmed by 1 H NMR, 31 P NMR, IR and elemental
analysis, and the thermal behaviors of PFR-8 was studied by TG and DSC respectively. The result
indicated that PFR-8 have high glass transition temperature (Tg=275.7 ℃ ), decomposed remarkably
between 322.4~330 ℃ , and weight lost rapidly in this temperature area. When it was heated to
600 ℃ , the charring residue was 31.4%. PFR-8
is expected to be a potential organophosphorus
flame retardant.
Acknowledgments
Financial support by National Basic Research Program of China (2003CB114400) and NNSFof
China ( 20372023)
REFERENCES
[1] Li Yu-Gui, Wang Jian-Ji, HAN Tao, Acta Chimica Sinica, 46,679-685, (1988).
[2] David W. A., Edwyn C. A., Leslie E. S., Poly. Deg. Stab., 45,399-408, (1994).
356
CH 3

P-116
THE IMPROVED METHOD FOR THE INDUSTRIAL SCALE PREPARATION OF
ADENOSINE CYCLOPHOSPHATE (cAMP)
Xiu Qiang Wang, Dong Chao Wang, Ran Xia, Zhi Guang Zhang, Hai Ming Guo, Gui Rong Qu*
College of Chemistry and Environmental Science, Henan Normal University, Xinxiang, Henan 453007, P. R.
China;Tuoxin Biochemical Technology & Science Co., Ltd. Xinxiang, Henan 453000, P. R. China, E-mail:
quguir@sina.com
cAMP (3) is a widely used drug to cure angina pectoris and myocardial infarct for its high
affinity and less side effect. It can modulate the differentiation of the cells, canceration and
reversion, as well as many other bio-physical processes. Thus, the demand for this compound has
been growing dramatically in the international market. Herein, we presented the improved method
for the industrial scale preparation for cAMP.
Treatment of adenosine (1) with phosphoryl trichloride (POCl3) in fresh distilled triethyl
phosphate at -5 o C for 2 hours afforded the key intermediate adenosine 5´-dichlorophosphate (2).
After adding ethyl acetate to the reaction mixture under stirring, we found that 2 precipitated from
the solution. To dissolve 2 in triethyl phosphate and add 0.04mol/L KOH aqueous and acetonitrile,
then neutralise it by 2mol/L HCl at 0 o C achieved 3 in 60% overall yield and more than 99% purity
after filtrating and recrystallization. The melting point and other spectra (IR, 1 H-NMR, 13 C-NMR,
31 P-NMR) were in accord with the standard sample. The advantage of this method included its low
cost, avoiding column chromatography, and the product could be prepared with moderate yield
together with high purity.
HO
O
N
N
NH 2
N
N
POCl 3
-5℃, 2h
Cl
O
P
Cl
O
O
357
N
N
NH 2
N
N
KOH/CH3CN 0℃
OH OH
OH OH
O P O OH
1 2
OH
3
Reference
[1] R. Keith Borden, Michael Smith, J. Org. Chem., 1966, 31: 3247-3258.
[2] Taguchi Y, Mushika Y, Bull. Chem. Soc. Jpn., 1957, 48: 1528-1532.
[3] Genieser K, Yoshikawa M, Synthesis, 1989, 1: 53-54.
[4] Kusashio K, Yoshikawa Y, Bull. Chem. Soc. Jpn., 1968, 41:142-149.
Project supported by the National Natural Science Foundation of China (No. 20372018).
O
O
N
N
NH 2
N
N

P-122
SYNTHESIS AND HERBICIDAL ACTIVITY OF Α- [2-( FLUORO-SUBSTITUTED
PHEMOXY)-PROPIONYLOXY] ALKYLPHOSPHONATES
Yan-Jun Li Hong-Wu He*
Key Laboratory of Pesticide & ChemicaBiology of Ministry of Education, Central China Normal UniversitWuhan
430079, People’s Republic of China, *Corresponding author
E-mail: hel208@mail.ccnu.edu.cn.
The title compound was synthesized by the reaction of O,O-dimethyl 1-hydroxyalkyl
phosphonate with 2-(fluoro-substituted phenoxy)propionyl chloride according to a literature
procedure. O,O-dimethyl 1-hydroxyalkylphosphonate can be obtained by the reaction of dimethyl
phosphite with several kinds of aldehydes using potassium fluoride and alumina (mass ratio was 1:1)
as catalyst with yield of 56-88%. The synthesis of the title compounds could be completed with
yield of 20-70% using triethylamine as catalyst and trap of acid . Structures of the 8 compounds
were confirmed by 1 HNMR, IR, MS spectra and element analysis. The results of preliminary
bioassay indicated that the title compounds exhibite better herbicidal activities.
X
Y
1) NaOH
2) HCl
OH
BrCH(CH 3)COOEt
K 2CO 3
358
X
Y
OCHCOOEt
CH 3
X
1) SOCl2 OCHCOOH
Y 2) (CH3O) 2POCH(OH)R
CH3 II
I
H 3CO
H 3CO
O
O
PCHOCCHO
R
CH 3
III
R=CH3,CCl3,4-CH3-Ph,4-F-Ph X,Y=2-F-H ,2-Cl-4-F
Acknowledgments
Financial support by National Basic Research Program of China (2003CB114400) and NNSFof
China ( 20372023)
References
[1] He, H.-W.. Chin. Chem. Lett. 9, 415–416(1998).
[2] He, H.-W.. Chin. J. Org. Chem. 23, 155–161 (2003).
[3] Brayer Jean Lowis, Taliani Laurent, Tessier Jean. EP376819, 1990
[4] Bleaker Springs, Paul Healbe. J.Org. Chem.,14(7),1165(1976)
[5] Francoise Fexier-Bullet, Maryvonne Lequitte. Tetrahedron Lett.27(30),3515-3516(1986)
X
Y

P-126
SYNTHESIS, CRYSTAL STRUCTURE AND BIOACTIVITIES OF DIMETHYL[(3,7-
DICHLOROQUINOLIN-8-YL CARBONYLOXY) ALKYL] PHOSPHONATE
Ying Liang Ya-Zhou Wang Hong-Wu He*
Key Laboratory of Pesticide & Chemical Biology of Ministry of Education,Central China Normal University, Wuhan
430079, People’s Republic of China. *E-mail: hel208@mail.ccnu.edu.cn
3,7-dichloroquinolin-8-ylcarbonyloxy alkylphosphonate was synthesized by the reaction of
3,7-dichloroquinoline-8-carbonyl chloride with O,O-Dimethyl-1-hydroxy alkyl phosphonates. The
preparation of title compounds could be completed with good yields of 60-80%, by adding
triethylamine(1.2 equiv) as catalyst and trap of acid. The best reaction time was 2-5 hours and the
temperature was 2-15℃. All 14 compounds were confirmed by 1 HNMR, IR, MS spectra and
element analysis. One of them was examined by the single crystal X-ray diffraction. The results of
preliminary bioassay indicated that the title compounds exhibited a little better fungicidal activities
than the starting compounds.
Cl
COCl
N
Cl
O
HC
(CH3O) 2P
R
OH
359
CHCl 3
Cl
Cl O
N
O H C
R
R=H, alkyl, Ph, substituted Ph, Furyl.
P OMe
O
OMe
Acknowledgments
This work was supported by the National Basic Research Program of China (No: 2003CB114400)
and the National Natural Science Foundation of China (No: 20372023).

P-128
THE INFLUENTIAL FACTOR ON SYNTHESIS OF L-PHE OLIGO-PEPTIDES
MEDIATED BY POCl3
Yingyan Yao 1 , Li Ma 1 , Kui Lu* 1 , Yufen Zhao 2
1.School of Chemistry and Chemical Engineering, Henan University of Technology, Zhengzhou 450052, China;
2.Department of Chemistry, Xiamen University, Xiamen 361005, China
Phosphorus play vital roles in the chemical evolution of life, The recent years, Self-assembly into
peptides for amino acids Mediated by inorganic phosphorus has become a focus of science research
[1,2] In this paper, the reactions of self-assembly into oligo-peptides for L-Phe mediated by
inorganic phosphorus were studied. To find the best experimental condition, the solvent, reaction
time, reaction temperature, the molar ratio of L-Phe and POCl3 were examined. These results were
found: the maximum length of peptides for L-Phe could reach hexapeptide, but time affected little
the reaction of self-assembly into oligo-peptides for L-Phe; The percent conversion of L-Phe in
THF was higher than that in 1,4-dioxane or acetonitrile, so THF was propitious to self-assembly
into peptides for L-Phe; Hoisting temperature could also speed the reaction and facilitate to produce
phosphoryl peptides, but too high(>50 ) would induce many ℃ side reactions; The reaction of
self-assembly into oligo-peptides would be speeded by increasing initial concentration of L-Phe. In
a word, the proper condition of direct synthesis was the molar ratio of L-Phe and POCl3 of 1 to 1,
reaction temperature of 40℃, reaction time of 2h and in THF as solvent. A series of mass peaks
corresponding to oligo-peptides of L-Phe were observed by electrospray ionization mass
spectrometry (ESI-MS).
Acknowledgements: The authors would like to thank the financial supports from the Chinese
National Science Foundation (No.20272055, 20572016), Henan Province Science Foundation for
Prominent Youth (No.0312000900) and Office of Education of Henan Province (No.
2006KYCX017, 200510459015).
360

References:
1 Lu, K.; Liu, Y.; Zhou, N.; Chen, Y.; Feng, Y.-P. ; Guo, X.-F.; Chen, W.; Qu, L.-B.; Zhao, Y.-F. Acta Chim. Sinica
2002, 60 , 372 (in Chinese).
2 Zhou, N.; Lu, K.; Liu, Y.; Chen, Y.; Tang, G.; Cao, S.-X.; Qu, L.-B.; Zhao, Y.-F. Rapid Commun Mass Sp 2002,16
(8) , 790
361

P-131
LONG-PERSISTENT FLUORESCENT FILMS OF EUROPIUM AND DYSPROSIUM
CO-DOPED ALUMINATES
Yuan Ming Huang, Fu-fang Zhou
Department of Applied Physics, Shantou University, Guangdong 515063, China
Flexible and long-persistent fluorescent thin films were obtained by casting polystyrene and
epoxy with fine particles of long persistent phosphorus aluminates, which were prepared by
combustion rare-earth dopants europium and dysprosium with aluminates at 600-800 o C. X-ray
diffraction and photospectrometer were employed to characterize the structures and optical
properties of the phosphorus aluminates in the flexible thin films. The flexibility of the thin films
was tested for the thin films with various compositions of the phosphorus aluminates, and the
effects of the two rare-earth dopants on the optical properties were also investigated. Based on the
excitation and emission spectra of the thin films, the mechanisms of the long-persistent fluorescence
were discussed. Our results have demonstrated that these phosphor-embedded flexible films can be
used as flexible and foldable phosphorus screens.
P-133
AB INITIO STUDY ON THE TOXICITY OF ORGANIC
PHOSPHORUS AGROCHEMICAL
Zhang Yu
College of Chemistry, Baotou Teacher’s College, Inner Mongolia
University of Science and Technology, Baotou 014030, China. E-mail: btzhangyu@yahoo.com.cn
Some organic phosphorus agrochemical have been studied with ab initio method. The bond
length and toxicity of the phosphorus compound present positive related that between the
phosphorus atom and the atom of the main functional group connect with each other. The total
atomic charge of the phosphorus atom and toxicity of the organic phosphorus agrochemical present
negative related.
Refrences
[1] Xu,Y.M.;Zheng,N. The domestic agrochemical application manual, Peking:Chinese agriculture original publisher
1990,4-51
[2] ChemHandbook3.0, Electronics version
362

P-136
PATTERN OF SEDIMENT PHOSPHORUS FRACTIONS IN A SHALLOW
WULIANGSUHAI LAKE, CHINA: EFFECTS OF MACROPHYTES
Zhenying Liu 1 , Zhaohui Jin 1 , Yawei Li 2 , Tielong Li 1 , Jiujun Gu 1 , Si Gao 1 , Xiaoyu Chai 1
1
College of Environmental Science and Engineering, Nankai University, Tianjin 300071, China;
2
Inner Mongolia Environment Protection Bureau, Hohhot 010018, China
Sediment phosphorus fractions and profile distribution at submerged macrophyte growth zone,
emergent macrophyte growth zone and open-water zone were studied in Wuliangsuhai Lake, China,
as well as the correlations among water content, grain size, and organic matter and P fractions.
Among three surveyed zones, the highest concentrations of most P forms occurred in the surface
sediment and the lowest between a depth of 12 and 22 cm, except HCl-P and NaOH-P. Sediment
phosphorus is mainly associated to inorganic forms (> 50%) in three surveyed areas, and the highest
value of IP in the surface sediment was obtained from submerged macrophyte growth zone.
Submerged and emergent macrophytes increased IP content by 107μg/g and 44μg/g in surface
sediment compared with open-water zone, respectively. Vertical profiles of IP in three surveyed
zones showed that the concentrations decreased from surface to12 cm depth and then increased.
There was a similar trend in the sediment profiles of OP and TP, but the highest concentration of
OP and TP in surface sediment was got from emergent macrophyte growth zone. Compared with
open-water zone, emergent macrophyte increased TP content by 455μg/g in surface sediment, while
submerged macrophyte enhanced TP content by 103μg/g in surface sediment. It was observed that
in macrophyte growth zones a strong linear correlation existed between organic matter and OP
(r>0.98), and the maximum concentrations of OP were present in the areas with maximum
concentrations of organic matter. Results show that, although rooted macrophyte could uptake
directly P from sediments, it is responsible for increasing internal P loading especially OP by
reducing current velocities, attenuating wave energy and generating organic residue in
Wuliangsuhai Lake.
Key words: phosphorus fractions, profile distribution, emergent macrophyte, submerged
macrophyte, open-water
363

P-166
NEW FUNCTIONALIZED PHOSPHORYL MEMBRANE CARRIERS OF ORGANIC AND
NONORGANIC SUBSTRATES
Krasnova N.S., Garifzyanov A.R., Cherkasov R.A.
Kazan State University, A.M. Butlerov Chemistry Institute, 420008, Kremlevskaya str. 18, Kazan, Russia
The methods of liquid and membrane extraction play the important role in technological
processes, connected with concentration and selective separating of mineral, organic and biological
substrates.
Functionalized derivatives of four-coordinated phosphorus such as trioctylphosphineoxide,
tributylphosphate and aminophosphoryl compounds were recommended as good membrane carriers.
The purpose of work presented was the study the influence of structure of phosphoryl compounds
on their membrane-transport properties.
With this aim the series of compounds R2P(O)R’, where R=2-EtHexO, R’=NBu2 (I),
R=2-EtHexO, R’=NEt2 (II), R=2-EtHexO, R’=NHBu (III), R=2-EtHexO, R’=NH(CH2)2NEt2 (IV),
R=Oct, R’= NBu2 (V), R=DecO, R’=CH2NBu2 (VI), 2-EtHexO, R’=O(CH2)2NEt2 (VII), 2-EtHexO,
R’=O(CH2)2NBu2 (VIII), have been synthesized. We have taken the sterically hindered substituents
to make sure the high lipophilycity of membrane carriers.
The compounds received differ with the dentaticity of the potential interaction with the substrates
being carried as well as with the basicity of phosphoryl group. Perchloric, tartaric and oxalic acids
have been chosen as substrates in this investigation. They are differ from each other by dissociation
degree and by the number of potential linkage centers. Monoethanolamine also has been chosen as
hidrofilic substrate wich is able to display both basic and proton-donating properties.
It is established that values of streams fall back in ranks VI>V>VII>VIII>IV>III>I≈II (perchloric
acid), VII>VI>V>I≈II>III (tartaric acid), V>VII>II>I≈IV>III>VI (oxalic acil),
VII>V>VI>VIII>II≈I≈III≈IV (monoethanolamine).
We revealed that the efficiency of the membrane transport growth parallel to both the increasing
of the phosphoryl unit bacisity and the participation of the additional coordination center in the
carrier-molecule.
The work was realized under financial support of RFBR (grant № 04-03-32906).
364

P-173
HIGH THROUGHPUT SCREENING UNDER Zinc-DATABASE AND SYNTHESIS A
DIALKYLPHOSPHINIC ACID AS A POTENTIAL KARI INHIBITOR
Liu Xinghai, Chen Peiquan, Guo Wancheng, Wang Suhua, Li Zhengming*
(The Research Institute of Elemento-Organic Chemistry, State-Key Laboratory of Elemento-Organic Chemistry, Nankai
University, Tianjin 300071, P.R. China)
Plants and microorganisms contain numerous enzymes that are potential targets for bioactive
compounds such as herbicides. Ketol-acid reductoisomerase (KARI) is the second key enzymes
involved the biosynthesis of the branched-chain amino acids: leucine, isoleucine and valine [1] . Our
research wants to discover new herbicides. In the past research, we discover a new sulfonylureas
herbicide — monosulfonylureas [2] .
Today, throughput screening HTS is a novel technique system in pesticide innovation with the
virtue of high efficiency, large-scale and automatics. Based on the reported crystal structure of
complexes of the enzyme KARI, 200 molecules were obtained with predicted high affinity for
KARI from ZINC-database(Drug-Like) searching, using program eHiTS [3] . A dialkylphosphinic
acid was docked with KARI and estimated the pKi = -5.235. The interaction pattern between the
titled compound and KARI was described. We synthesized the title compound. The KARI activity
is under testing.
The synthesized route of the title compound and the Docking result is listed in scheme 1 and
figure 2 and 3.
Si Cl NH3 Si Si H2POONH4 ClCH2COOCH3 HP(OSiMe)3
N
N(C
H
2H5) 3
O
O
O
O
O
P
O Si C 2H 5OH O
365
O
Scheme 1. The synthetic route of title compound
Fig. 2 spinage KARI active site with title compound Fig.3 Superimposition of the docked
conformation of title modeled into the binding pocket compound and IpOHA in complex with
spinage KARI
Acknowledgements
O
O
O
P
OH
HO
HO
O
O
O
P
OH

This work was funded by the National Basic Research Program of China (Grant No. 2003
CB114406) and the high performance computing project of Tianjin Ministry of Science and
Technology of China (grant number 043185111-5).
Reference
1. R.G. Duggleby, S.S. Pang, Acetohydroxyacid synthase, J. Biochem. Molec. Biol. 2000,33,1–36.
2. Z.M. Li, G.F. Jia, L.X. Wang, Sulfonylurea compound herbicide, CN1106393, 1995,8,9
3. http://www.simbiosys.ca/ehits/
366

P-181
A STUDY ON THE ORGANIC COMPOUNDS CONTAINING GERMANIUM AND
PHOSPHOURS USING EI MASS SPECTROMETRY
Liu Ruoyu 1 , Ye Yong 1 , Liao Xincheng 1 ,Qu Lingbo 1 , Zhao Yufen 1,2
1.The Key Laboratory of Chemical Biology and Organic Chemistry of Henan Province, Department of Chemistry,
Zhengzhou University, Zhengzhou 450052, China;
2.The Key Laboratory for Bioorganic Phosphorus Chemistry and Chemical Biology, Ministry of Education, Department
of Chemistry School of Life Sciences and Engineering, TsinghuaUniversity, Beijing 100084, China
A series of organic compounds containing germanium and phosphours are studied by EI or
ESI-MS. The positive or negative ions for these compounds are reported . The fragmentation
pathways were investigated in details and its characteristics have been summarized. The
fragmentation ions produced from EI or ESI provide complementary informatiom for the structure
elucidation.
References
[1] Ye Yong: [Master Paper]. Tianjin. Chemistry Department of Nankai University. 1998
[2] Zhu Xiaofei, Ye Yong, Zeng Qiang. Recent Advances of Anticancer Active Organic Compound Containing
Phosphorus and Germanium. Tianjin Chemical Industry, 2002; 3:pp4~6
367

P-189
INVESTIGATION ON A HYDROXYL OXYGEN MIGRATION OF
N-PHOSPHORYL DIPEPTIDES BY ELECTROSPRAY
IONIZATION MASS SPECTROMETRY
Huang Xiantong, Tang Guo, Lin Kan, Chen Yushen, Zhaoyufen *
The Key Laboratory for Chemical Biology of Fujian Province, Department of Chemistry and College of Chemistry and
Chemical Engineering, Xiamen University, Xiamen 361005, P. R. China.
A novel rearrangement reaction with a hydroxyl oxygen migration was observed in the
electrospray ionization tandem mass spectra of N-diisopropyloxyphosphoryl dipeptides . A possible
mechanism was proposed and supported by the MS/MS study. It was found that metal ions could
catalyze the rearrangement through a seven-membered ring intermediate.
All peptides and their derivatives were synthesized in this laboratory by literature methods and
phosphorylated according to our published methods. 1 chemicals for syntheses were purchased from
Sigma (Shanghai, China)
O
O
O
O
O
P
HN
CH
R1 O
HN
P
M+Na
O
O
O
C
HN
Na
OH
R 2
O
368
O O
HN
P
O
R 1
O
O
HN
P
O
R1 ONa
H
O
C
M+Na M+Na
R 1
O
HN H
P C
ONa
C O
R 2
HN
-
R 2
OH
O R 2
ONa
C
N
H
OH
Na
M+Na
Scheme1. proposed rearrangement mechanism for N-diisopropyloxyphosphoryl dipeptides
Acknowledgement: the financial supports from the Ministry of Education Key Project (104201) and
Fujian Key Foundation of Science and Technology (C03100)
References
[1] Ji GJ, Xue CB, Zeng JN, Li LP, Chai WG, Zhao YF, Synthesis 1988; 6: 444.
N
H
O
C
O
H 2 N
R 2
O
R 2
O

P-191
INVESTIGATION ON THE PEPTIDES FORMATION FROM AMINO ACIDS REACTED
WITH TRIMETAPHOSPHATE BY LC-MS
Xiang Gao 1 , Yan Liu 1 , Pengxiang Xu 1 , Guo Tang, Yufen Zhao 1,2 *
1. The Key Laboratory for Chemical Biology of Fujian Province, Department of Chemistry, College of Chemistry and
Chemical Engineering, Xiamen University, Xiamen, 361005, P. R. China
2. The Key Laboratory for Bioorganic Phosphorus Chemistry, Ministry of Education, Department of Chemistry, School
of Life Sciences and Engineering, Tsinghua University, Beijing, 100084, P. R. China
It was suggested that probably inorganic condensed phosphates, such as polyphosphate and
trimetaphosphate, would have been the essential materials for the prebiotic evolution which
preceded the emergence of life on the earth [1, 2]. In recent years, alternative methods for amino
acids and small peptides analysis without derivatization have been proposed. Ion-pair
chromatography and reversed-phase liquid chromatography were widely used to separate amino
acids and small peptides by employing perfluorinated carboxylic acids as ion-pairing reagents on a
silica based column. Furthermore, electrospray tandem mass spectrometry (ESI-MS) was an
effective direct detector for analysis of underivatized amino acids and peptides due to its high
sensitivity and incomparable specificity.
Figure 1. The ESI-MS spectra for each amino acid treated with P3m. (A): Glycine reacted with P3m;
(B): L-Alanine reacted with P3m; (C): β-Alanine reacted with P3m; (C): γ-Aminobutyric acid reacted
with P3m
The condensation reactions of single amino acid or each pair of amino acids such as glycine,
L-alanine, β-alanine and γ-aminobutyric acid with sodium trimetaphosphate (P3m) were
reinvestigated by electrospray ion-trap mass spectrometry (ESI-MS) and high performance liquid
chromatography. It was found when treated by P3m only at the presence of α-amino acid did form
peptide. Without α-amino acid, the β-amino acid or γ-amino acid could not form peptide either by
themselves or with their mixtures under the same conditions. These experimental results might
suggest that phosphate prefers choosing α-amino acids to produce the peptides for the origin of life.
References
[1] J. Rabinowitz, J. Flores, R. Krebsbach, G. Rogers, Nature 1969, 224: 795-796
[2] Y. Yamagata, H. Watanabe, M. Saitoh, T. Namba, Nature 1991, 352: 516-519.
369

Symposium 8
Special Session Dedicated to the Late Professor L. Horner

KL-4
OLEFINATION REACTION IN ORGANIC SULFUR CHEMISTRY AND SYNTHESIS OF
NATURAL PRODUCTS
Marian Mikolajczyk
Center of Molecular and Macromolecular Studies, Polish Academy of Sciences 90-363 Lodz, Sienkiewicza 112, Poland
371

IL-3
2-HYDROXY- AND 2-AMINO-FUNCTIONAL ARYLPHOSPHINES-SYNTHESIS,
REACTIVITY AND USE IN CATALYSIS
J. Heinicke, a W. Wawrzyniak, a N. Peulecke, a B. R. Aluri, a P.G. Jones, b S. Enthaler, c M. Beller c
EMA-University Greifswald a (Germany), Technical University Braunschweig b (Germany),
Leibniz-Institute of Catalysis Rostock c (Germany)
Syntheses of 2-phosphinophenoles [1] and 2-hydroxy-1,1’-biaryl-2-phosphines [2] and separation
of diastereoisomeric (1S)-camphanoates of asymmetric derivatives were studied. The absolute
configuration of two pure enantiomers was determined by crystal structure analysis. Other
camphanoates preferred cocrystallization of different isomers in the asymmetric unit. First catalytic
studies displayed ee’s up to 60%.
P
OSiMe3 R2
R1 nBuLi
SiPPOPhos-tBuMe: R1 =Me, R2 =tBu
SiPPOPhos-tBupTol: R1 =tBu, R2 =p-Tol
SiPPOPhos-tBuMes: R1 =tBu, R2 =Mes
SiPPOPhos-An2: R1 =R2 =o-An
R 1
P
OLi
R2
Cl
O
O
O
R 1
372
P
O
R2
O
CaPPOPhos-tBuMe: R1 =Me, R2 =tBu
CaPPOPhos-tBupTol: R1 =tBu, R2 =p-Tol
CaPPOPhos-tBuMes: R1 =tBu, R2 =Mes
CaPPOPhos-An2: R1 =R2 =o-An
N-Substituted 2-phosphinoanilines, synthesized via anilino- or anilidophosphonates, have been
used in the synthesis of N-alkyl- or N-aryl-1,3-benzazaphospholes. These are particularly stable
annulated heterophospholes [3]. Reaction with t-BuLi allows lithiation in 2-position without attack
at the P=C bond and introduction of various functional groups. However, addition is also possible.
This opens a novel access to heterocyclic ethylene-bis(phosphine) ligands.
Reference
[1] J. Heinicke, N. Peulecke, M. Köhler, M. He, W. Keim, J. Organomet. Chem., 2005, 690, 2449.
[2] P. Wawrzyniak, PhD thesis, Greifswald, 2006.
[3] R. K. Bansal, J. Heinicke, Chem. Rev. 2001, 101, 3549-3578. B.R. Aluri, unpublished.
O
O

IL-4
ENANTIOSELECTIVE SYNTHESIS OF P-CHIROGENIC PHOSPHORUS COMPOUNDS
VIA THE EPHEDRINE-BORANE COMPLEX METHODOLOGY
Sylvain Juge
Inst. Chim. Mol. Université de Bourgogne,UMR CNRS 5620, 9 av. A. Savary,
21078 Dijon, France; Fax 33 3 80 39 60 98 Email: Sylvain.Juge@u-bourgogne.fr
In spite of the pioneering work of Horner 1 and Knowles, 2 phosphines bearing chirality on the
phosphorus atom have not been very used in asymmetric catalysis until now, mainly due to the
difficulty of their stereoselective preparation. Nevertheless, in the recent past, significant progresses
have been realized for the P-chirogenic compounds, likewise owing to the ephedrine-borane
methodology. 3
BH 3
Ph
P
Ph
O Me
N
Me
2
(+)-ephedrine
1
R 1 Li
BH 3
R P
Ph
3
1
N
Me
OH
Me Ph
P R
Ph
1
HX
X
4
tBuLi
The principle of this method is based on two key step:
- the diastereoelective preparation of an oxazaphospholidine borane complex 2 derived from
(+)-ephedrine 1, in one step.
- the regio and stereoselective P-O bond cleavage by reaction with an organolithium reagent to
afford the aminophosphine borane 3.
The acidolysis or the methanolysis of the compound 3 affords then the corresponding
P-chirogenic chlorophosphine boranes 4 (X=Cl) or phosphinite boranes 4 (X=OMe) respectively,
which are used as P-chirogenic electrophilic building blocks. Recently, a new development was
showed, with the preparation of the phosphide boranes 5 by metal-halide exchange starting from the
chlorophosphine boranes 4, affording thus useful P-chirogenic nucleophilic building blocks.
The efficiency of this methodology is demonstrated by the possibility of preparing various
kinds of phosphorus compounds in high e.e. bearing the chirality on phosphorus atom (bulky or
functionnalized phosphines, secondary phosphines, phosphinites, aminophosphines...). Moreover,
as the purification of free phosphorus trivalent compounds is not always possible, the direct use of
their borane complexes for the synthesis or the catalysis, is a useful alternative. Thus, phosphonium
salts, phosphorylated (P=O) or thiophosphorylated (P=S) derivatives, could be stereoselectively
prepared from borane complexes without isolation of the P (III) intermediate. In the same way, the
organophosphorus borane complexes give also the opportunity to use unstable ligands in
coordination chemistry or to generate catalysts.
References
1) L. Horner, H. Siegel, H. Büthe Angew. Chem. Int. Ed. 1968, 942.
373
BH 3
Li
BH 3
P
5
R
Ph
1

2) W.S. Knowles, M.J. Sabacky J.C.S. Chem. Commun. 1968, 1445.
3) a) Moulin, D.; Bago, S.; Bauduin, C.; Darcel, C.; Jugé, S. Tetrahedron: Asymmetry 2000, 11, 3939. b) C. Darcel, El
B. Kaloun, R. Merdès, D. Moulin, N. Riegel, S. Thorimbert, J. P. Genêt, S. Jugé J. Organomet. Chem., 2001, 624, 333.
c) S. Humbel, C. Bertrand, C. Darcel, C. Bauduin, S. Jugé Inorg. Chem. 2003, 42, 420. e) J.M. Camus, J. Andrieu, P.
Richard, R. Poli, C. Darcel, S. Jugé Tetrahedron: Asymmetry 2004, 15, 2061. f) C. Bauduin, D. Moulin, El B. Kaloun,
C. Darcel, S. Jugé J. Org. Chem. 2003, 11, 4293. g) C. Darcel, D. Moulin, J.C. Henry, M. Lagrelette, P. Richard, P.
Harvey, S. Jugé Eur. J. Org. Chem. 2007, in press.
374

IL-5
UMPOLUNG IN HORNER REACTION: PHOSPHORAMIDATES AS A SOURCE OF
P-CHIRAL ORGANOPHOSPHATES
Wojciech Jacek Stec and Janina Baraniak
Department of Bioorganic Chemistry, Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences,
112 Sienkiewicza Str., 90-363 Łódź, Poland
The discovery that organophosphorus ylides and phosphonate anions ract with carbonyl
electrophiles leading to olefins had an enormous impact on the art of organic synthesis. Although
similar reactions of numerous phosphoramidate anions have been also studied, interest in the
synthesis of unsaturated C=N systems has overshadowed interest in the fate of the second product
of the Horner-Wadsworth-Emmons reaction, namely, dialkyl (diaryl) phosphates or
phosphorothioates.
However, the growing interest in the stereospecific synthesis of P-chiral organophosphates and
phosphorothioates, and especially the demonstration of the use of phosphorothioates as tools for
investigating the mode of action of numerous phosphoryl transfer catalyzing enzymes, focused the
attention of several research groups on methods for the stereospecific preparation of P-chiral
phosphates and phosphorothioates. In this laboratory studies were undertaken on the application of
the Horner-Wadsworth-Emmons reaction using covalent diastereomeric phosphoramidates for the
preparation of enantiomeric organophosphates, organophosphorothioates, and organophosphoroselenoates.
Special attention was focused upon the stereochemical consequences of this reaction,
also called by the authors PN→PX conversion (X= S, Se, O) [1]
It turned out that the development of our synthetic approach involving the preparation of P-chiral
phosphoramidates followed by the replacement of an amidate function by oxygen, sulfur, or
selenium, opened the way to the stereospecific preparation of a variety of P-chiral derivatives of
phosphorus acids, including numerous biophosphates and their analogues [2]
Application of title reaction for the preparation of diastereomerically pure P-chiral cyclic
nucleotide analogues (phosphorothioates, phosphoroselenoates, phosphoroselenothioates,
isotopomeric 18O-phosphates), and P-chiral nucleoside monophosphate analogues, as well as
dinucleoside phosphate analogues (phosphorothioates, methanephosphonates and their thio- and
seleno-congeners) will be presented.
Reference
[1].W. J. Stec: Wadsworth-Emmons Reaction Revisited. Acc. Chem. Res., 1983, 16, 411
[2].L. A. Woźniak and A. Okruszek: The stereospecific syntheses of P-chiral biophosphates and their analogs by the
Stec reaction. Chem. Soc. Rev. 2003, 32, 158-169.
375

IL-6
SYNTHESIS AND APPLICATIONS OF PHOSPHONATES PREPARED FROM
ELECTROPHILIC PHOSPHORUS REAGENTS
David F. Wiemer
Department of Chemistry, University of Iowa, Iowa City, IA 52242, USA . E-mail: david-wiemer@uiowa.edu
Classical methods for synthesis of β-keto phosphonates and α-phosphono esters and lactones rely
upon phosphorus nucleophiles for formation of the carbon-phosphorus bonds. To complement these
traditional strategies, and provide access to novel phosphonates not readily available via these
methods, we have explored approaches that employ phosphorus electrophiles and carbon
nucleophiles. For example, P(V) electrophiles react with enolates derived from cyclic ketones to
afford the vinyl phosphates, but in some cases the cyclic vinyl phosphates will rearrange to β-keto
phosphonates upon reaction with excess strong base. Enolates derived from lactones and some
esters undergo parallel reactions. In contrast, P(III) electrophiles can react with enolates directly at
the carbon terminus, and subsequent oxidation will afford the β-keto phosphonate or α-phosphono
esters/lactones. Variations on these strategies have been used to provide a variety of synthetic
intermediates for use in reactions like the Horner-Wadsworth-Emmons condensation, as well as to
prepare phosphonate analogues of natural phosphates. The preparation of specific target compounds
as well as some further applications of these phosphonates will be presented.
376

IL-7
DEVELOPMENT OF NOVEL CHIRAL PHOSPHORUS LIGANDS FOR
ENANTIOSELECTIVE HOMOGENEOUS AND HETEROGENEOUS CATALYSIS
Kuiling Ding
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of
Sciences, 354 Fenglin Road, Shanghai 200032 Fax: +86-21-6416-6128. E-mail: kding@mail.sioc.ac.cn
Development of practical protocols for asymmetric synthesis of optically active compounds
represents a great challenge in the area of chiral chemistry, in which the efficiency and the recycle
of the chiral catalysts are key issues. Two strategies for the development of practical asymmetric
catalysis will be discussed in this presentation. The first part of this presentation will focus on the
design, synthesis and application of chiral catalysts composed of phosphorous ligands for
homogeneous asymmetric reactions. [1]
RO 2C
CO 2R
O
R
N
N
O
O
377
R'
P N
R'
Ar2P PAr2 R
Y O X
DICP DpenPhos
CydamPhos
up to 99% yield and >98.9% ee
for Pd-catalyzed allylic substitution
up to 99% yield and >99% ee
for Rh(I)-catalyzed hydrogenations
up to 99% yield and >99% ee
for Rh(I)-catalyzed hydrogenation
Y
N
N
O
X
O
O
Z
P N
Z
The second part will present a conceptually new strategy, i.e. “self-supporting” approach, for
the immobilization of homogeneous catalysts through self-assembly of chiral multi-topic ligands
and metal ions without using any support. The success of this strategy will be demonstrated in
heterogeneous asymmetric hydrogenation reactions of functionalized olefins and ketones using
self-supported chiral phosphorous ligand/metal catalysts. [2]
+
+ +
multitopic chiral
phosphorous ligands
metallic ion
n
self-supported catalysts
References
[1] (a) Zhao, D.; Ding, K. Org . Lett. 2003, 5, 1349-1351. (b) Zhao, D.; Sun, J.; Ding, K. Chem. Eur. J. 2004, 10,
5952-5963. (c) Zhao, D.; Wang, Z.; Ding, K. Synlett. 2005, 2067-2071. (d) Zhao, B.; Wang, Z.; Ding, K. Adv. Synth. Cat.
2006, 348, 1049-1057. (e) Jing, Q.; Sandoval, C. A.; Wang, Z,; Ding, K. Eur. J. Org. Chem. 2006, 3606-3616. (f) Jing,
n

Q.; Zhang, X.; Sun, J.; Ding, K. Adv. Synth. Cat. 2005, 347, 1193-1197. (g) Liu, Y.; Ding, K. J. Am. Chem. Soc. 2005,
127, 10488-10499. (h) Liu, Y.; Sandoval, C. A.; Yamaguchi, Y.; Zhang, X.; Wang, Z.; Kato, K.; Ding, K. J. Am. Chem.
Soc. 2006, 128, 14212 - 14213.
[2] (a) Wang, X.; Ding, K. J. Am. Chem. Soc. 2004, 126, 10524-10525. (b) Liang, Y.; Jing, Q.; Li, X.; Shi, L.; Ding, K.
J. Am. Chem. Soc. 2005, 127, 127, 7694-7695. (c) Liang, Y.; Wang, Z.; Ding, K. Adv. Synth. Cat. 2006, 348, 1533-1538.
(d) Shi, L.; Wang, X.; Sandoval, C. A.; Li, M.; Qi, Q.; Li, Z.; Ding, K. Angew. Chem. Int. Ed. 2006, 45, 4108-4112. (e)
Ding, K.; Wang, Z.; Wang, X.; Liang, Y.; Wang, X. Chem. Eur. J. 2006, 12, 5188-5197.
Acknowledgement: I am grateful to the National Natural Science Foundation of China, the Major Basic Research
Development Program of China (Grant no. 2006CB806106), and CAS for financial support of this work.
378

O-34
CHIRAL PHOSPHORUS-CONTAINED CALIXARENES
S.O.Cherenok, V.I.Boiko, V.I.Kalchenko
Institute of Organic Chemistry, Natl. Acad. of Sci. of Ukraine, 02660, Kyiv-94, Ukraine. E-mail: vik@bpci.kiev.ua
www.ioch.kiev.ua/calix
Macrocyclic compounds are ubiquitous as synthetic receptors in bio-organic and supramolecular
chemistry. Incorporation of phosphorus-containing binding groups on the macrocyclic platform
enable supramolecular interactions to be defined a priori, having broad ramifications for chemistry,
physics, biology and material science. This paper presents synthesis and functional properties of
phosphorus-containing chiral calixarenes having three-dimensional molecular cavities, within the
context of molecular recognition and bio-activity.
Two types of phosphorus-containing chiral calixarenes are discussed. They are: (i) calixarenes
that have chirality induced by the asymmetric placement of achiral (or chiral) substituents at the
upper or lower rim of the macrocycle [1,2] , and (ii) compounds functionalized by chiral
substituents [3,4] .
Calix[4]arene bis-α-hydroxyphosphonic acids as pure Meso and Racemic forms were synthesized
through the reactions of diformylcalixarenes with thrialkylphosphites or sodium dialkylphosphites [4] .
Chiral calix[4]arene α-aminophosphonic acids were obtained through the diastereoselective
Pudovik-type addition of sodium diethylphosphites to the chiral calixarene imines [4] .
NR
X
Y X Y
RHN
*
R = CH(Ph)CH3 ( -)(S)
R = CH(Ph)CH *
3 (+)(R)
(EtO) 2P(O)H Na
EtO
EtO
R
O
P
H
N
X
Y X Y
N
H
*
*
(SR, RS)
(RS, SR)
R
OEt
P
OEt
O
H 2
Pd(C)
379
EtO
EtO
X = OH, Y= OPr
N
H 2
O
O
P *
NH2 HO
HO
P *
X
Y X Y
*
(R, R)
(S, S)
OEt
P
OEt
O
1. Me3SiBr 2. MeOH
N
H 2
X
Y X Y
A difference in the host-guest complexation parameters of aminoacids or dipeptides with
Racemic and Meso forms of cailxarene bis-hydroxyphosphonic acid is observed [3] . The calixarene
aminophosphonic acids show inhibitory activity toward porcine kidney alkaline phosphatase that
strongly depends on the absolute configuration of the α-carbon atoms [4] .
References
[1] Tairov M.A., Vysotsky M.O., Kalchenko O.I., Pirozhenko V.V., Kalchenko V.I. J. Chem. Soc. Perkin Trans. 1. 2002.
1405-1411.
[2] Boyko V.I., Shivanyuk A., Pyrozhenko V.V., Zubatyk R.I., Shishkin O.V., Kalchenko V.I. Tetrahedron Letters. 2006.
47. 7775-7778.
[3] Zielenkiewicz W., Marcinowicz A., Cherenok S., Kalchenko V., Poznański J.. Supramolecular Chemistry. 2006.
18. 167-176.
[4] Cherenok S., Vovk A., Muravyova I., Shivanyuk A., Kukhar V., Lipkowski J., Kalchenko V. Organic Letters.
2006. 8. 549-5
*
(R, R)
(S, S)
NH 2
OH
P
OH
O

AUTHOR INDEX

A
Abdrakhmanova, L. M. 40
Adachi, Kazutaka 113
Adam, M. S. S. 155
Agou, Tomohiro 24
Ahn Vu, Erika Shaffer 30
Aladzheva, Inga M. 62
Aleksandrova, Anastasia V. 14,111
Aleksanyan, D. V. 87
Alfonsov, Vladimir A. 41, 70, 75,78, 90, 352
Allen, Christopher W. 167
Aluri, B. R. 155, 372
Amerkhanova, N. K. 179
Angermann, J. 282
Antipina, M. Yu. 291
Arduengo, Anthony J. 161
Armentano, Maria Francesca 189
Artemkina, I. M. 165
Artyushin, O. I. 20,291
Asai, Kazuhide 43
Ashkenazi, Nissan 39
Auclair, M. L. 118,119
Ausín, Cristina 190
Au-yeung, Steve C. F. 236
B
Babashkina, Maria G. 149
Badeeva, E. K. 178
Bagautdinova, R. Kh. 6
Baier, I. 47
Bala, Joy Lynn F. 302
Balassa, Annamária 143
Balueva, A. S. 146, 166
Bao, Rui 293, 294,338, 349
Baraniak, Janina 186, 375
Baranov, S. V. 142
Barnett, B. L. 259, 278
Barten, Jan 28
Batra, Vinod K. 222
Batyeva, Elvira S. 178, 352
Bauduin, C. 156
Bayandina, Еvgenia V. 90
Bayardon, J. 228
Beard, William A. 222
Beasley, Duane 276
Beaton, Sarah K. D. 50
Beaucage, Serge L. 190
381
Belaj, Ferdinand 54
Beller, M. 372
Bendikov, Michael 39
Berdnik, I. V. 61
Berdnikov, E. A. 114
Bergsträßer, H. 136
Berlicki, Łukasz 279
Beylis, Irena 67
Bezgubenko, L. V. 83
Bilge, Selen 13
Blackburn, G. Micheal 2
Blann, Kevin 329
Bod, Henriette de 329
Bódis, Ádám 44
Bogdanov, A. V. 22, 49
Boiko, V. I. 379
Bontemps, S. 130
Borisova, Yu. Yu. 179
Bouhadir, G. 130
Bourissou, D. 130
Bozkurt, S. 112
Breuer, Eli 67, 271
Brunet, Ernesto 331
Bruzik, Karol 194
Brzezińska Rodak,
Małgorzata
19, 27
Budnikova, Yu. H. 61, 177, 321
Burck, S. 247
Burel, Laure 274, 292, 301
Burilo, A. R. 18, 47
Burkov, K. A. 244
Burnaeva, L. A. 35
Burnaeva, L. M. 40, 179
Buzykin, B. I. 49
Bykhovskaya, Olga V. 62
C
Cai, Fei 73,171
Cai, Puqin 307, 309
Calichman, Michael 167
Cao, L. H. 273
Cao, Lifeng 298
Cao, Shuxia
68, 102, 207, 229, 347,
351
Cao, Weina 91, 212, 217
Capon, J. F. 148
Caporali, Maria 170
Carlos, Juan 331
Cartier, Dominique 274
Caruthers, Marvin H. 188
Chachkov, D. V. 99, 242

Chai, Xiaoyu 363
Chandra, Richard 327
Chandrasekaran, A. 159
Chattopadhyaya, Jyoti 268
Chen, Caibao 97
Chen, Guanhua 238
Chen, Gui 131
Chen, Li 185
Chen, Peiquan 365
Chen, Ruyu 16, 108, 206, 269, 336
Chen, Weizhu 232, 308
Chen, Xiaobao 353
Chen, Xiaolan
72, 82, 106, 202, 204, 224,
258, 302
Chen, Yan 100
Chen, Yushen 368
Chen, Zhao 338, 349
Cheng, Fang 310
Cheng, Hisn-Mei 245
Cheong, Yuenki 94, 107
Cherenok, S. O. 214, 284, 379
Cherkasov, Rafael A. 35, 60, 114, 115, 140, 142,
149, 254, 295, 364
Cherkin, K. Yu. 21
Chernega, Aleksandr N. 120
Chmutova, G. A. 75
Chu, Sanyan 245
Chuiko, A. L. 76, 290
Clément, Jean Claude 274, 292, 301
Colson, A. 228
Congiardo, Laura K.
Byington
30
Cosgrove, Nichola E. 80
Cristau, Henri Jean 139
Cui, Zhanwei 108, 206, 269
Czernicka, Anna 277
D
Darcel, C. 118, 119, 156, 228
Delépine, Pascal 274, 292, 301
Deme, János 44
Demiriz, Semsay 13
Demkowicz, Sebastian 38
Didkovskii, N. G. 14
Dielmann, F. 173
Dimukhametov, M. N. 40
Ding, Kuiling 377
Ding, Mingwu 283
Ding, Yixiang 153
Dix, I. 117
Dixon, John T. 329
382
Dobrynin, A. B. 49, 243
Dobrynin, Alexey B. 70
Docherty, Gordon 326
Dogadina, Alla V. 14, 111
Dong, Zhenrong 131
Du, Ya 73, 171
Duan, Chunjian 204
Duan, Haifeng 150, 152
Dudás, Eszter 56
Duncanson, Philip 94, 107
Dunford, J. 259, 278
Durova, Oxana 189
E
Ebetino, F. H. 259, 278
Ekici, S. 112
Engelhardt, Johnnie 276
Enthaler, S. 372
Ermolaev, Yevgeniy S. 352
Evdokimov, A. G. 259
F
Fang, Hua 122, 230, 257, 304, 305
Fang, Meijuan 304, 305
Feng, Dexin 16
Feng, Yezhen 216
Férec, Claude 274, 292, 301
Field, Martin J. 235
Floch, P. L. 129
Fogassy, Elemér 44
Forlani, Giuseppe 279
Frant, Julia 67
Freese, Dirk 323
Freund, Amy 167
Freytag, Matthias 84, 145
Friboulet, Alain 189
Fu, Boqiao 196
Fu, Chuan 116
Fu, Hua 157
Fujie, Michio 43
G
Gabibov, Alexander G. 189
Gabrielli, William 329
Gaffney, Barbara L. 266
Ganushevich, Yulia 170
Gao, Feng 92

Gao, Jingxing 131
Gao, Si 363
Gao, Xiang 369
Gao, Yuxing 232, 308
Garifzjanov, Airat R. 35, 295, 364
Gataulina, Alfiya N. 140
Gataulina, I. F. 254
Gates, Derek P. 168
Gavrilova, E. L. 18
Gazizova, A. A. 99, 242
Genkina, G. K. 48
Giamarchi, Philippe 274, 292, 301
Gilheany, D. G. 45
Gledhill, Alexandra C. 176
Gloaguen, F. 148
Gololobov, Gennady 189
Gomès, M. 119, 156
Gonsalvi, Luca 170
Goodman, Myron F. 222
Gorenstein, David G. 276
Goss, Wieslawa 199
Govorun, Vadim 189
Grabowiecka, Agnieszka 279
Grajkowski, Andrzej 190
Graznova, T. V. 321
Gregoriades, L. J. 173
Griffiths, D. Vaughan 77, 94, 107, 280
Groombridge, H. J. 280
Gryaznova, T. V. 177
Gryshkun, E. V. 32
Gu, Jiujun 363
Guan, Jintao 100
Gubaidullin, A. T. 179
Gudat, D. 247
Guillouzic, Anne Françoise 139
Guliaiko, Irina V. 32, 63
Guo, Chun 307
Guo, Haiming 357
Guo, Wancheng 365
Guo, Yanchun 68, 102, 351
Guo, Yingcen 103
Guo, Zhongcheng 180
H
Habicher, W. D. 47
Hajdók, I. 247
Hall, Roger G. 317
Han, Daxiong 341
Han, Jiecai 334
383
Han, Libiao 8, 297
Han, Qianwei 266
Han, Xiao 94
Han, Ying 345
Haritha, Buchammagari 43
Hartsock, Robert 30
Harvey, P. D. 156
Hayakawa, Yoshihiro 265
He, Dacheng 225
He, Hongwu
81, 86, 93, 213, 318,
330, 342, 356, 358, 359
He, Jing 325
He, Liangnian 73, 171
He, Lijun 354
He, Zhengjie 52
Heinicke, J. 117, 155, 372
Hendrix, William H. 320
Henry, J. C. 118, 119, 156
Hettel, Sonja 335
Heydt 136
Hey-Hawkins, E. 10, 36, 146, 166, 174, 243
Higham, L. J. 45
Hilfinger, John M. 303
Hiney, R. M. 45
Hiresova, Renata 201
Hissler, Muriel 162
Hofmann, U. 136
Hogan, J. 259
Hoge, Berthold 335
Hohl, Raymond J. 286
Hohmann, Emília 56
Holland, Eric C 197
Holmes, Robert 159
Höltzl, T. 246
Hor, T. S. Andy 134
Hou, Guohua IV, 55
Hou, Jianbo 253
Hu, Anfu 227
Hu, Jia 233
Hu, Liming 151
Hu, Thomas Q. 327
Hu, Xiaolian 346
Hu, Yanggen 283
Huang, Chaobiao 181
Huang, Jing 196
Huang, Shiwen 187
Huang, Xiantong 123, 368
Huang, You 16, 336
Huang, Yuanming 362
Hulisani Maumela, M 329

I
Ionin, Boris I. 14, 111
Ishmaev, E. A. 99, 242
Ito, Shigekazu 84, 145, 161
Ivkova, Gul’nara A. 35, 179, 295
Izawa, Masatoshi 37
J
Jaffrès, Paul-Alain 148, 274, 292, 301
James, Brian R. 327
Jaspers, D. 112
Ji, Tao 122
Ji, Yubin 288
Ji, Zhiliang 305
Jia, Guochen 135
Jia, Yixia 150, 152
Jiang, Lan 69, 345
Jiang, X. D. 241
Jiang, Yuyang
157, 221, 300, 307, 309, 311,
312
Jin, Linhong 275
Jin, Peiyuan 203
Jin, Weiwei 97
Jin, Xuanye 223
Jin, Zhaohui 363
Johnson, B. P. 173
Jones, P. G. 117, 155, 372
Jones, Roger A. 266
Ju, Yong 101, 203, 223
Ju, Zhiyu 66, 346
Juanes, Olga 331
Jugé, Sylvain 118, 119, 156, 228, 373
Juhlin, Lars 169
K
Kachkovskyi, G. A. 285
Kachkovskyi, G. O. 32
Kaczmarek, Renata 186
Kafarski, Paweł 19, 27, 200, 277, 279, 281
Kakuda, K. I. 241
Kalchenko, V. 214
Kalchenko, V. 214, 284, 379
Kaljurand, Ivari 28
Kang, Suk Jin 17
Kano, Naokazu 57
Kapustin, E. G. 83
Karasik, A. A. 10, 146, 166, 243
Karton, Yishai 39
Kashemirov, Boris A. 70, 90, 222, 259, 278, 302,
384
Kataev, А. V.
303
174
Kataeva, Olga N. 70, 75, 78, 90, 146, 243
Kato, Kiyotoshi 37
Kavanagh, K. 259
Kawashima, Takayuki 5, 24, 57, 85
Kaziev, G. Z. 273
Kee, Terence P. 80, 176
Keglevich, György 44, 56, 143, 252
Kerényi, Andrea 143
Kevill, Dennis N. 17
Khailova, N. A. 6
Khakimov, Maxim V. 295
Khasiyatullina, N. R. 22
Khusainov, M. A. 254
Khusainov, N. G. 114, 254
Kibardina, Ludmila K. 6, 78
Kilic, Zeynel 13
Killian, Esna 329
Klimek-Ochab, Magdalena 19, 27
Kniazeva, I. R. 47
Knight, D. Andrew 30
Kobayashi, Junji 24, 85
Koh, Han Joong 17
Koidan, Georgyi N. 120
Kolodiazhna, A. O. 32, 110
Kolodiazhnyi, Oleg I. 32, 63, 71, 89, 110, 285
Kolomeitsev, Alexander A. 28, 31
Kolotylo, M. V. 46
Kononets, L. 290
Konovalov, A. I. 18, 21, 22, 47, 49
Konovalova, I. V. 40, 179
Koppel, Ilmar A. 28
Koppel, Ivar 28
Koroteev, M. P. 273
Körtvélyesi, Tamás 143, 252
Kostyuk, Aleksandr N. 12
Kotorova, Yu. Yu. 40
Kozlov, A. V. 146, 243
Kozlov, V. A. 20, 87
Krakowiak, Agnieszka 186
Krasil’nikova, E. A. 18
Krasnov, S. A. 177, 321
Krasnova, N. S. 35, 364
Krivolapov, D. B. 22, 49, 243
Kubicky, M. 228
Kukhar, V. P. 110, 214, 284, 285, 290
Kulikov, D. V. 146, 166
Kultyshev, Roman 222
Kuriata, Renata 19
Kursheva, L. I. 178

Kütt, Agnes 28
L
Lach, J. 117
Lagrelette, M. 156
Lamarche, François 292, 301
Lammertsma, Koop 272
Larionova, O. А. 88
Latypov, Sh. K. 146, 243
Lauréano, H. 118
Lawson, M. A. 278
Lee, Philip W. 315
Lehn, Pierre 274, 292, 301
Leito, Ivo 28
Lejczak, Barbara 19, 27
Lescop, Christophe 162
Li, Chao 141
Li, Dongpin 103
Li, Gang 232
Li, Heping 344
Li, Rui 209, 350
Li, Tielong 363
Li, Wenfeng 72
Li, Wenpeng 312
Li, Xiaopeng 151
Li, Xinyong 97
Li, Ya 69, 345
Li, Yan 101
Li, Yanjun 358
Li, Yanmei 215, 233, 267
Li, Yanyun 131
Li, Yawei 363
Li, Zhengming 365
Li, Zhengqiu 356
Liang, Hongze 145
Liang, Ying 359
Liao, Xincheng
66, 68, 102, 207, 229, 258,
298, 346, 347, 351, 367
Lin, Jianyun 341
Lin, Kan 123, 253, 368
Lissner, F. 247
Litvinov, I. A. 22, 179, 243
Liu, Aiping 334
Liu, Chengmei 293, 294, 338, 349
Liu, Chenwei 53
Liu, Cunjiang 298
Liu, Feng 300
Liu, Hongxia 221, 300
Liu, Hui 330
385
Liu, Jihong 207
Liu, Jinming 351
Liu, Kai 203
Liu, Lianna 304
Liu, Mian 221, 300
Liu, Peng 227
Liu, Ruoyu 229, 258, 367
Liu, Shenghua 100
Liu, Tanglin 16
Liu, Wei 313
Liu, Xiangqian 204
Liu, Xiaoxia 230, 231
Liu, Xinghai 365
Liu, Yan 225, 230, 231, 369
Liu, Zhenying 363
Liu, Zhongdong 333
Livantsov, M. V. 26
Livantsova, L. I. 26
Lönnecke 36, 146, 174, 243
Lork, Enno 28
Loutsenko, S. 119
Lozinsky, M. O. 76
Lozynsky, M. 290
Lu, Jiansha 202, 207
Lu, Kui
91, 104, 209, 212, 216, 217,
250, 251, 289, 296, 340, 350
Lü, Liang 325
Lü, Mingxiu 212, 217
Lu, Ping 275
Luiz, T. Arun 138
Luo, Shuna 305
Luo, Zhuanxi 348
Luxon, Bruce A. 276
Lyssenkob, K. A. 291
M
Ma, Li
91, 209, 212, 217, 289, 296,
340, 350
Ma, Xinpeng 95, 96
Ma, Yuan 313
Mäemets, Vahur 28
Magdeev, I. M. 61, 321, 352
Makarova, M. V. 291
Makker, Sudesh P. 189
Manoharan, Muthiah 195
Marchenko, Anatoliy P. 120
Marcinowicz, A. 214
Maron, L. 130
Martiyanov, Yevgeniy M. 140
Mastryukova, Tatyana A. 20, 48, 62, 87
Mathey, Francois 1

Matsukawa 58, 241
Matveeva, E. V. 20
Maumela, Chris 329
Mayer, Beatrix 143
McConnell, Ann E. 329
McKenna, Charles E. 70, 90, 222, 259, 261, 278,
302, 303
Meenen, Ellen Van 15
Meng, Xianggao 100
Merkle, R. 173
Metivier, Pascal 133
Metlushka1, Kirill E. 70
Meunier Prest, R. 228
Mével, Mathieu 274, 292, 301
Miao, C. X. 171
Miao, Zhiwei 108, 206, 269, 336
Midollini, Stefano 170
Midoux, Patrick 274
Milaeva, E. R. 26
Miluykov, V. А. 174
Miqueu, K. 130
Mironov, V. F. 40, 88, 179
Mironov, V. F. 21, 22, 49
Mischenko, I. M. 285
Miszuk, Marta 19
Miyake, Hideaki 57, 84
Miyoshi, Katsuhiko 172
Mlynarz, P. 200
Mo, Wenyan 93
Moiseev, Dmitry 327
Momota, Hiro 197
Montier, Tristan 274, 292, 301
Moonen, Kristof 15
Morata, G. 118, 119
Morgan, David H. 329
Morita, Noboru 37, 113
Morozov, V. I. 88
Morse, Herbert C. III 189
Morvan, D. 148
Mostovaya, O. A. 114, 254
Moszner, N. 282
Moulin, D. 156
Mucsi, Zoltán 252
Murakami, Fumiki 37
Murakami, Midori 37
Muravyova, I. 214, 284, 290
Muslinkin, A. A. 61
Mussai, Naama 67
Muzychka, O. 214, 284
Myund, L. A. 244
386
N
Nabiullin, V. N. 61
Nakafuji, Shinya 85
Nakamura, Satoki 43
Nakazawa, Hiroshi 172
Natsagdorj, Amgalan 13
Naumov, R. N. 166, 243
Naumova , A. A. 18
Nawrot, Barbara 199
Nerio, Edward 197
Nesterenko, Valery P. 328
Nesterov, Vitaly V. 32, 71, 89
Nguyen, M. T. 246
Ni, Feng 116, 255
Niecke, Edgar 112, 127
Nieger, M 112, 163, 247
Nifantyev, E. E. 273
Niimi, Taishi 43
Nikitina, Liliya E. 60, 115
Nishide, Katsunori 145
Niu, Mingyu 157
Nixon, John 7
Nixon, Tracy D. 176
Nizamov, Il’nar D. 140, 352
Nizamov, Il’yas S. 60, 115, 140, 352
Nongodlwana, Palesa 329
Novák, Tibor 44, 252
Novikova, O. P. 26
Novikova, Z. S. 99
Nuti, F. 228
Nyulászi, László 249
O
Odinets, I. L. 20, 87, 291
Onys’ko, Petro P. 33, 42, 46
Orlandini, Annabella 170
Oshikawa, Tatsuo 43
Osipov, S. N. 20
Özbolat, A. Helten 163
P
Padda, Ranbir 326
Pan, Canping 316
Papini, A. M. 228
Pedersen, Lars C. 222
Peng, Aiyun 51
Peng, Hao 342
Perez, J. M. 163

Peruzzini, Maurizio 170
Peterson, Larryn W. 303
Petrovskii, Pavel V. 48, 62, 87
Peulecke, N. 117, 372
Pichon, Chantal 274
Pierluigi, Barbaro 170
Pietrusiewicz, K. Michal 25
Pinchuk, Aleksandr M. 12, 120
Pipko, S. E. 83
Pirat, Jean Luc 139, 287
Pirozhenko, V. V. 46
Platova, E. V. 178
Pokross, M. E. 259
Poliakov, D. V. 23
Ponomarenko, Natalia A. 189
Popovich, Yan Ye. 352
Povolotskii, Mark I. 83, 120
Poznanski, J. 214
Pretorius, Mari 329
Prishchenko, A. A. 26
Pudovik, M. A. 6, 18, 47, 75
Punegova, Lyudmila N. 90
Pustovit, Yurii M. 120
Q
Qiang, Liming 347
Qiao, Renzhong 59, 141, 343
Qiu, Jinjun 293, 294, 338, 349
Qu, Guirong 357
Qu, Lingbo
72, 74, 82, 106, 121, 202,
204, 224, 367
R
Rachon, Janusz 38
Rao, M. N. Sudheendra 138
Rassukana, Yu. V. 33, 42, 46, 244
Re, Lige 196
Réau, Régis 162
Rebowska, Beata 199
Reddy, Maddali
Kasthuraiah
43
Reddy, Valluru Krishna 43
Regitz, M 136
Rehmann, Nina 335
Reich, Reuven 67
Rémond, E. 228
Ren, Haiping 289, 340
Ren, Qingyun 81
Ren, Yong 100
387
Reshetnyak, Andrey V. 189
Reznik, V. S. 352
Richard, P. 118, 119, 156
Rodima, Toomas 28
Rogalyov, A. E. 23
Romanova, I. P. 88
Röschenthaler, Gerd
Volker
20, 23, 28, 31
Roze, C. 259, 278
Rudzińska, E. 248
Rusanov, E. B. 83
Russell, R. Graham G. 259, 278, 302
Rybakov, S. M. 114
Rybalkinab, E.Yu. 291
Rydzewska, A. 200
S
Sadkova, Dilyara N. 70
Sadykova, Yu. M. 47
Safin, Damir A. 149
Salt, Michael C. 77
Sasaki, Kohji 37
Sasaki, Mitsuru 319
Sasaki, Shigeru 37, 113
Scheer, Manfred 173
Schindler, József 44
Schoeller, Wolfgang W. 240
Schollhammer, P. 148
Schroeder, G. 200
Segall, Yoffi 39
Sekiguchi, Satoshi 84
Serebryakova, Marina 189
Sergeenko, Gulnur G. 352
Shao, Shuangxi 69, 345
Sharma, Pradeep K. 34
Sharova, E. V. 20
Shatalova, N. I. 18
Sheiko, S. Yu. 285
Shen, Lili 298
Shen, Weiyi 131
Sheng, Xijun 356
Shevchenko, I. V. 23
Shi, Deqing 339, 353
Shi, Kaiqi 69, 345
Shi, Wenping 64, 205
Shi, Xiaona 202
Shih, Alan H. 197
Shipov, A. E. 48
Shivanyukb, A. 284
Shock, David D. 222

Shumbera, Mark 276
Shyshkov, O. A. 31
Sibgatulin, Dmitrii A. 12
Sidorov, Lu. N. 244
Sinitsa, A. A. 33
Sinitsa, Anatoly D. 42, 46, 83
Sinyashin, Oleg
10, 88, 146, 166, 170, 174,
177, 178, 243, 321, 352
Sipos, Melinda 56, 143
Sliwinska, S. 200
Smetannikov, Y. V. 165
Smith, Martin B. 137
Sofronov, Artiem V. 60, 115
Sokolov, Felix D. 142, 149
Song, Baoan 275
Song, Deyu Hu 275
Song, Yingjun 92
Spiridonova, Yu. S. 166
Stankevič, Marek 25
Stawinski, Jacek 201
Stec, Wojciech Jacek 186, 199, 375
Stegbauer, W. David 30
Stevens, Christian V. 15
Streubel, R. 163
Sugiya, Masashi 29
Sun, Manji 224
Sun, Shuting 116
Sun, Yanting 216
Surya Prakash, G. K. 222
Suyama, Takuya 43
Svyashchenko, Yurii V. 12
Szekrényi, Anna 56
Szymelfejnik, Mateusz 38
T
Takács, Daniella 56
Takahashi, Masaki 43
Takano, Keiko 172
Talan, Alexey S. 35, 295
Talarmin, J. 148
Tanchuk, S. V. 284, 285, 290
Tang, Chuchi 95, 96, 98
Tang, Guo
122, 123, 124, 253, 310,
368, 369
Tang, Li'na 91
Tang, Wei 153
Tao, Qin 124
Tarasova, N. P. 164, 165
Tatarinov, D. A. 21
Taylor, Helen V. 77
Tazeev, D. I. 177
388
Terent’eva, S. A. 6, 75
Tian, J. S. 171
Timofeevac, T. V. 291
Timosheva, Natalya V. 159
Tomilov, A. P. 321
Tong, Huaxiang 286
Totsuka, Hirono 43
Tramontano, Alfonso 189
Triffitt, J. T. 278
Tsai, Ming-Daw 260
Tschirschwitz, S. 36
Tsunashim, Katsuhiko 29
Turigin, V. V. 321
U
Ujj, Viktória 44
Upton, Thomas G. 222
V
Varaksina, E. N. 21
Varghese, Babu 138
Vereshchagina, Ya. A. 99, 242
Veszprémi, T. 246
Vilesov, A. S. 165
Virieux, David 139, 287
Volle, Jean Noël 287
Volochnyuk, Dmitrii M. 12
Vorob’eva, D. V. 20
Voronkov, M. G. 242
Vovk, A. I. 214, 284, 285, 290
W
Wada, Takeshi 263
Wagner, Carston R. 183
Waltho, Jonathan P. 237
Wang, Bin 336
Wang, Bo 51
Wang, Chungui 95, 96, 98
Wang, Dongchao 357
Wang, Fang 151
Wang, Haiyan 341
Wang, Hui 59
Wang, J. Q. 171
Wang, Jianing 225
Wang, Jie 336
Wang, Jinquan 73
Wang, Junli 180

Wang, Meimei 354
Wang, Suhua 365
Wang, T. 273
Wang, Tao 86, 348
Wang, Tingting 92
Wang, Tongjian 253, 310
Wang, Wenhu 92
Wang, Xiaohui 297
Wang, Xiuqiang 357
Wang, Yazhou 359
Wang, Yue 309, 311
Wang, Yulin 325
Wang, Z. 219
Wärme, Rikard 169
Wawrzyniak, W. 372
Webster, Charles E. 239
Wen, Tingbin 135
Werner, M. A. 136
Widera, Kinga 199
Wieczorek, Michał 186
Wiemer, Andrew J. 286
Wiemer, David F. 208, 286, 376
Willemse, Alex 329
Williams, D. Bradley G. 144
Williams, Gareth 299
Wilson, Samuel H. 222
Witt, Dariusz 38
Wojcik, Marzena 199
Wu, Guoqiang 325
Wu, Huaping 334
Wu, Nana 354
Wu, Xianli 68, 102
Wu, Xiuling 354
X
Xia, Aibing 50
Xia, Ran 357
Xia, Z. 259, 278
Xia, Zhidao 302
Xiao, Qiang 223
Xiao, Weihong 223
Xiao, Wenjing 97, 103, 330
Xie, Hongxue 354
Xie, Jianhua IV, 55
Xie, Yali 102, 351
Xie, Zhenhua 300, 311, 312
Xu, Jun 64, 205
Xu, Pengxiang 227, 369
Xu, Ruidong 180
389
Xu, Shengzhen 283
Xu, Xinyuan 95, 96, 98
Xu, Xuemei 151
Xue, Wei 275
Y
Yakhvarov, Dmitry 170
Yamamichi, Hideaki 58, 241
Yamamoto, Yohsuke 58, 241
Yamashita, Mitsuji 43
Yang, Junliang 346
Yang, Song 275
Yang, Xianbin 276
Yang, Xun 51
Yang, Yan 333
Yao, Yingyan VII, 104
Yaouanc, Jean Jacques 148, 274, 292, 301
Yarmieva, Liliya N. 90
Yarullin, R. S. 352
Ye, Qiaoyun 69
Ye, Yong 66, 229, 258, 298, 346, 367
Yin, Zhengming 66
Yorke, Jake 50
Yoshifuji, Masaaki 37, 84, 113, 145, 161
Yu, Eric 327
Yu, Gang 43
Yu, Guang'ao 100
Yu, José S. 208
Yu, Yaqin 16
Yu, Zhenrong 181
Yuan, Chengye 262
Yuan, Jinwei 72, 106, 202
Yusupova, G. G. 88
Z
Zabirov, Nail G. 142, 149
Zade, Sanjio S. 39
Zanobini, Fabrizio 170
Zeng, Zhiping 255, 257
Zeuner, F. 282
Zhang, Baojun 121
Zhang, Bo 52
Zhang, Hongbo 343
Zhang, Hongyu 204
Zhang, Hui 131
Zhang, Jianchen 64, 205, 347
Zhang, Jianfeng 108, 206, 269
Zhang, Lihe 184

Zhang, Linglin 211
Zhang, Liping 74
Zhang, Liuji 121
Zhang, Nan 307, 309, 311, 312
Zhang, Peizhuo 307, 309
Zhang, Peng 300
Zhang, Shufeng 218
Zhang, Sixing 68
Zhang, Ting 224
Zhang, Xueqing 131
Zhang, Xumu 128
Zhang, Yu 362
Zhang, Yujin 288
Zhang, Yuping 275
Zhang, Zhaoying 266
Zhang, Zhiguang 357
Zhao, Canfang 221
Zhao, Dongxin 250, 251
Zhao, Guofeng 95, 96
Zhao, Jianwei 266
Zhao, Junfeng 68
Zhao, Wenjie 250, 251, 296
Zhao, Yufen
68,91, 116, 122, 123, 124,
157, 171, 215, 227, 230,
231, 253, 255, 257, 267,
289, 304, 305, 308, 309,
310, 343, 368, 369
390
Zheltukhin, Viktor F. 70
Zhen, Xi 193
Zheng, Jinyun 218
Zhong, Shangbin 346
Zhou, Fufang 362
Zhou, Libin 181
Zhou, Qilin 55, 125, 150, 152
Zhou, Xiang 196
Zhou, Zhaoliang 325
Zhou, Zhenghong 95, 96, 98
Zhu, Bo 348
Zhu, Jiaqi 334
Zhu, Shoufei IV, 55, 150, 152
Zhuo, Renxi 187
Zielenkiewicz, W. 214
Ziganshin, Rustam 189
Zon, Gerald 192
Zou, Ruyi 66, 207, 298, 346
Zuo, Na 213
Zweni, Pumza 329
Żymańczyk-Duda, Ewa 19, 27