Total Synthesis Highlights

More documents

Recommendations

Info

85. Total Synthesis of Ingenol The total synthesis of the tetracyclic Euphorbia tetraol ingenol 3 reported by Keiji Tanino of Hokkaido University (J. Am. Chem. Soc. 2003, 125, 1498.) illustrates the power of diastereoselective carbocationic rearrangements, as exemplified by the conversion of 1 to 2. The construction of the tricyclic epoxide depended on several highly diastereoselective transformations. The addition of lithio t-butyl acetate to ketone 4 proceeded to give 5 as a single diastereomer, even though the ketone is flanked by a quaternary center. The authors speculate that lithium chelation with the methyl ether directed addition. Even more spectacular was the cyclization of the propargylic acetate 7 to 10. The Co complex activated the acetate for ionization, while at the same time establishing the proper geometric relationship for bond formation. Dissolving metal reduction of the Co complex then gave the alkene. The elegant pinacol rearrangement of 1 to 2, mediated by (ArO) 2 AlCH 3 , exposed a ketone that might usually need to be protected. In this case, however, the ketone is so buried in the inside-outside ingenol skeleton that it is unreactive. After several further manipulations, a spectacular osmylation of the diene 12 led to ingenol 3, in an overall 45-step sequence. The ingenol 3 prepared by this route was racemic. It is interesting to speculate how one might efficiently prepare 4 or its precursors in enantiomerically-pure form.
86. Total Synthesis of the Galbulimima Alkaloid GB 13 Lew Mander of the Australian National University recently reported (J. Am. Chem. Soc. 2003, 125, 2400. ) the total synthesis of the pentacyclic alkaloid GB 13 3, which had been isolated from the bark of the rain forest tree Galbulimima belgraveana. In the course of the synthesis, he took full advantage of benzene precursors, while at the same time carefully establishing each of the eight stereogenic centers of 3. The core tricyclic ketone 1 was assembled by Birch reduction of 2,5-dimethoxybenzoic acid, followed by alkylation with 3-methoxybenzyl bromide, to give 4. Acid-catalyzed electrophilic cyclization of 4 gave the tricyclic ketone 5, which on decarboxylation and protection gave 1. Diazo transfer to 1 followed by irradiation in the presence of bis-(trimethylsilyl)amide led to ring contraction with concomitant carbonyl extrusion, to give 7. Dehydration to the nitrile followed by selenation then set the stage for a highly diastereoselective ytterbium-catalyzed Diels-Alder reaction, to give, after reduction and protection, the pentacyclic intermediate 2. Intermediate 2 appears to have two extraneous carbons, the red nitrile and the blue carbon in the aromatic ring. In fact, the blue carbon was carried all the way through, to appear as the α-methyl group on the piperidine ring. Birch reduction of 2 deleted the now-superfluous nitrile, and reduced the aromatic ring, to give, after hydrolysis, the enone 10. Eschenmoser fragmentation of the intermediate epoxy ketone then gave the keto alkyne 11. The subsequent condensation with hydroxylamine followed by reduction proceeded with spectacular (but anticipated) stereocontrol, to establish the three stereogenic centers of the trisubstituted piperidine ring. Oxidation of 12 then gave the enone 3.
Page 1 and 2:
近年来完成的天然产
Page 3 and 4:
The starting point for the synthesi
Page 5 and 6:
The side chain nitrile was prepared
Page 7 and 8:
Carbonylative coupling of 1 and 2 l
Page 9 and 10:
6. The Overman Synthesis of Briarel
Page 11 and 12:
There were two remaining problems i
Page 13 and 14:
The iodide 19 was enantiomerically
Page 15 and 16:
To complete the synthesis of 3, it
Page 17 and 18:
The assembly of 2 began with the li
Page 19 and 20:
The synthesis of the aromatic porti
Page 21 and 22:
Pseudolaric Acid B (3) would be der
Page 23 and 24:
Reduction of the ketone then set th
Page 25 and 26:
The absolute configuration of 1 was
Page 27 and 28:
The keto phosphonate 16 for the las
Page 29 and 30:
Nakamura reagent delivered the ally
Page 31 and 32:
21. The Overman Syntheses of Nankak
Page 33 and 34:
The benzyloxy aldehyde 1 was prepar
Page 35 and 36:
Debenzylation of 11 followed by ace
Page 37 and 38:
The Hoveyda Synthesis of (-)-Clavir
Page 39 and 40:
eduction of 8 delivered the primary
Page 41 and 42:
The seemingly simple task of conver
Page 43 and 44:
fermentation of halogenated aromati
Page 45 and 46:
The octaene 1 was assembled from fo
Page 47 and 48:
The starting point for the preparat
Page 49 and 50:
Several aspects of this synthesis a
Page 51 and 52:
To achieve the syn relative (and ab
Page 53 and 54:
The diol 6 is C 2 -symmetrical, but
Page 55 and 56:
The last challenge was the establis
Page 57 and 58:
(+)-Discodermolide (3), a potent an
Page 59 and 60:
Evans auxiliary-controlled homologa
Page 61 and 62:
39. The Clark Synthesis of Vigulari
Page 63 and 64:
The preparation of 1 began with the
Page 65 and 66:
The preparation of 2 began with Cu-
Page 67 and 68:
With 3 in hand, what remained was a
Page 69 and 70:
44. The Padwa Synthesis of Asphidop
Page 71 and 72:
The aldehyde 1 was in fact not isol
Page 73 and 74:
47. The Nicolaou Synthesis of Plate
Page 75 and 76:
The enantiomercially-pure cyclopent
Page 77 and 78: Although the tandem ring closing me
Page 79 and 80: procedure, exposure of the diene 12
Page 81 and 82: Two such reagents, easily prepared
Page 83 and 84: The enantiomerically-pure imine 2 w
Page 85 and 86: Addition of 2-propenyl lithium to t
Page 87 and 88: The synthesis of 1 started with two
Page 89 and 90: ing system of vindoline, appropriat
Page 91 and 92: An additional stereogenic center is
Page 93 and 94: 60. Synthesis of the Potent FBBP12
Page 95 and 96: The enantiomerically-pure fragments
Page 97 and 98: Ullman coupling of 3 with the aryl
Page 99 and 100: Sordaricin (2) is the aglycone of s
Page 101 and 102: The alcohol 5 was the common interm
Page 103 and 104: Overall, this elegant synthesis is
Page 105 and 106: 3:1 mixture. That 1 was the major d
Page 107 and 108: The enantiomerically-pure intermedi
Page 109 and 110: Deprotection and acid-catalyzed cyc
Page 111 and 112: 72. Total Synthesis of (±)-Sordari
Page 113 and 114: The ester 2 has a trans 6-5 ring fu
Page 115 and 116: The enantioselective Cu-catalyzed c
Page 117 and 118: 77. Catalytic Asymmetric Synthesis
Page 119 and 120: Three-carbon ring expansion was car
Page 121 and 122: 80. Synthesis of (-)-Strychnine The
Page 123 and 124: The enantiomerically-pure aldehyde
Page 125 and 126: 83. Synthesis of (+)-Phomactin A Th
Page 127: The transient 5-9-5 ketone 8 has tw
show all

Total Synthesis Highlights

Create successful ePaper yourself

Delete template?

Save as template?