Total Synthesis Highlights

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The dihydronaphthalene 1 was prepared by Diels-Alder cycloaddition of the diene 5 to the benzoquinone 6, the preparation of which had been reported by Nicolaou in the course of a previous synthesis of (-)-colombiasin A (4). Silylation of the cycloadduct followed by selective hydrolysis gave the ketone 7. The ketone was converted to the enol triflate 8, which was reduced with triethylsilane to give racemic 1. Exposure of 1 to 2 in the presence of the DOSP Rh catalyst, designed by Davies, delivered the two adducts 8 and 9. These were carried together to the alcohols 10 and 11, which were separated. The overall yield of diasteromerically- and enantiomerically-pure 11 from racemic 1 was 34%. This was 68% of theoretical, since was derived from only one of the two enantiomers of 1. Homologation of 11 to the diene followed by desilylation under oxidative conditions led to the quinone 12. Followed the precedent of Rychnovsky, on heating 12 was converted to the Diels-Alder adduct 13. Demethylation then gave (-)-colombiasin A (4). The tetracyclic triketone (-)-elisapterosin B (14), also a Pseudoterogoria elisabethae diterpene, is the intramolecular [5 + 2] cycloaddition product from 12. Again following a Rychnovsky
procedure, exposure of the diene 12 to BF 3 etherate led directly to 14, accompanied by minor amounts of the methyl ether 13. 51. The Ready <strong>Synthesis</strong> of (-)-Nigellamine A 2 The nigellamine alkaloids, represented by (-)-nigellamine (3), dolabellane diterpenes isolated from black cumin, apparently have lipid metabolism promoting activity. Joseph M. Ready of UT Southwestern Medical Center has described (J. Am. Chem. Soc. 2006, 128, 7428.) the first synthesis of a nigellamine, (-)-nigellamine A 2 (3). Key steps in the synthesis include an enantioselective cyclization to prepare 1, and the Cr-mediated cyclization of the aldehyde 2. (-)-Nigellamine A 2 (3) has an angularly substituted trans ring fusion. The key to the synthesis was the preparation of the angularly-substituted cis-fused lactone 1. The absolute configuration of 1 was set by the Pd-mediated S N 2' cyclization of the malonate 6, which proceeded in 95% ee. Equally important was the seemingly mundane iodine-mediated cyclization of 7 to 8. This one transformation differentiated the two esters of 6, secured the relative configuration of one of the two secondary alcohols of 3, and established the requisite cis ring fusion of the lactone 1. Nucleophilic displacement of the iodide 8 failed, but two-carbon homologation to the alkyne could be accomplished by the free radical Fuchs procedure. There were intial difficulties with the Negishi methylation/iodination of the terminal alkyne, as the Cp 2 ZrCl 2 reacted preferentially with the lactol. Remarkably, repeating the reaction in the presence
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近年来完成的天然产
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The starting point for the synthesi
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The side chain nitrile was prepared
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Carbonylative coupling of 1 and 2 l
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6. The Overman Synthesis of Briarel
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There were two remaining problems i
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The iodide 19 was enantiomerically
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To complete the synthesis of 3, it
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The assembly of 2 began with the li
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The synthesis of the aromatic porti
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Pseudolaric Acid B (3) would be der
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Reduction of the ketone then set th
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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: Although the tandem ring closing me
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 and 128: The transient 5-9-5 ketone 8 has tw
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86. Total Synthesis of the Galbulim
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Total Synthesis Highlights

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