Total Synthesis Highlights

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Controlled desilylation of 11 followed by selective oxidation delivered the seco acid 12. It had previously been shown by others that some cyclic protecting groups facilitate macrolactone formation, while others do not. Fortunately, the two cyclic protecting groups of 12 served well, and the macrolactonization proceeded efficiently. Protecting group removal and reductive unmasking of the hydroxy ketone then delivered erythronolide A (4). Overall, this elegant synthesis is a showcase for the iterative use of the 1,3-dipolar cycloaddition of enantiomercially-pure allylic alcohols for the preparation of extended arrays of acyclic stereogenic centers. 57. The Boger Route to (-)-Vindoline The Vinca-derived vinblastine (2a) and vincristine (2b) are still mainstays of cancer chemotherapy. The more complex half of these dimeric alkaloids, vindoline (1), has in the past presented a formidable challenge for total synthesis. Dale L. Boger of Scripps, La Jolla has developed (Org. Lett. 2005, 7, 4539.) a strikingly simple solution to this problem, based on sequential cycloaddition. The starting point for the synthesis was N-methyl 6-methoxytryptamine (3), an improved preparation of which is described by the authors. This was extended to 4, which was then cyclized to 5, and acylated with 6 to give 7. On heating, 7 cyclized to 8, which lost N 2 to give the zwitterion 9. Addition of the intermediate 9 to the indole then gave 10. In one reaction, the entire
ing system of vindoline, appropriately oxygenated, was assembled! The precursor 7 was flat, so it offered no opportunity for chiral synthesis. Fortunately, 10 and ent-10 proved to be very easy to resolve by chiral chromatography. To complete the synthesis, the δ-lactam 11 was oxygenated to 12. Conditions for desulfurization of the derived thiolactam also effected debenzylation, to give, after acetylation, the ether 13. Pt-mediated hydrogenolysis gave 14, which was dehydrated to vindoline (1). A complementary synthetic route, based on the E isomer of 6, and so leading through the ether 15, is also described. Although slightly longer, this approach was about as efficient as the route via 11.
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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
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The benzyloxy aldehyde 1 was prepar
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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: The synthesis of 1 started with two
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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