Total Synthesis Highlights

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A variety of dolabellanes, some of which show substantial physiological activity, have been isolated from natural sources. E. J. Corey of Harvard University has introduced (J. Am. Chem. Soc. 2005, 127, 13813. ) a unfied approach to the dolabellanes, represented by isoedunol (3), based on the designed rearrangement of the mesylate 1 to 2. The key to this approach was the stereocontrolled construction of the cyclobutane 1. The starting material was the racemic iodo acetonide 4 derived from farnesol. Alkylation of 5 using the Seebach protocol followed by hydrolysis led the methylthiomethyl ether 7. The ester was converted to the hydroxy cyclopropane 8 by the Kulinkovic procedure. On activation with Me 3 Al, 8 was smoothly carried on to the enantiomerically-pure cyclobutanone 9. The ring expansion must not be proceeding by full ionization, as carbocation formation would have led to the racemic product. The aldehyde derived from 9 was cyclized with SmI 2 to the trans diol 10. In medium ring derivatives such as 10, one substituent on a ring carbon will be inside, and the other will be outside. The conformation of 10 is such that formation of the mesylate from the secondary alcohol led to migration of the more substituted cyclobutane bond, delivering 11. It follows that the conformation of the diol 12 will be flipped, to keep the OH outside the ring. Formation of the mesylate from the secondary alcohol of 12 led cleanly to migration of the less substituted cyclobutane bond, to give the desired cyclopentanone 2.
Addition of 2-propenyl lithium to the cyclopentanone 2 gave the dolebellane isoedunol (3). Deoxygenation converted 3 to the β-araneosene ( dolabellane13). This strategy for the construction of the dolabellanes may open a route for the preparation of the cytotoxic dolabellanes clavulactone (14) and clavirolide (15). 55. Adventures in Complex Indole <strong>Synthesis</strong>: (-)-Fischerindole I, (+)-Fischerindole G and (+)-Weltwitindolinone A Phil S. Baran of Scripps La Jolla has described (J. Am. Chem. Soc. 2005, 127, 15394.) an elegant entry to the complex indole-derived natural products (-)-fischerindole G (1), (+)-fischerindole I (2) and (+)-weltwitindolinone A (3). The starting point for the preparation of 1 and 2 was the epoxide 4 of R-carvone. Enolization followed by opening with vinyl magnesium bromide 5 delivered the alcohol 6. The yield of this reaction was modest, but it directly provided 6, with all of the non-indole carbon skeleton of 1, suitably oxidized, in enantiomerically-pure form.
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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
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The keto phosphonate 16 for the las
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Nakamura reagent delivered the ally
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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: The enantiomerically-pure imine 2 w
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
Page 129: 86. Total Synthesis of the Galbulim
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Total Synthesis Highlights

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