Total Synthesis Highlights

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Under anhydrous conditions, the oxide derived from the allylic selenide 12 did not rearrange. On the addition of water, the rearrangement proceeded smoothly. Protection and hydroboration converted 13 into 14. The bulk of the folded molecule protected the exo methylene of 14, so hydrogenation followed by protection and oxidation delivered 15. Conjugate addition of indole to 15 set the stage for oxidation and bis-methylenation to give 17. Selective Ru-mediated cross coupling with 18 followed by deprotection then completed the synthesis of (-)-Anominine (4), which proved to be the enantiomer of the natural product. D. F. Taber, Org. Chem. Highlights 2011, March 7. URL: http://www.organic-chemistry.org/Highlights/2011/07March.shtm 2. The Boger Synthesis of (-)-Vindoline The periwinkle-derived alkaloids vinblastine (2a) and vincristine (2b) are still mainstays of cancer chemotherapy. The more complex half of these dimeric alkaloids, vindoline (1), presents a formidable challenge for total synthesis. Building on his previous work (Org. Lett. 2005, 7, 4539.), Dale L. Boger of Scripps, La Jolla devised (J. Am. Chem. Soc. 2010, 132, 3685.) a strikingly simple solution to this problem, based on sequential cycloaddition.
The starting point for the synthesis was the ester 3, derived from D-asparagine. This was extended to 4, condensation of which with 5 gave the enol ether 6. 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 ring system of vindoline, appropriately oxygenated, was assembled, with the original stereogenic center from D-asparagine directing the relative and absolute configuration of the final product. To complete the synthesis, the pendant carbon on 11 had to be incorporated into the pentacyclic skeleton. After adjusting the relative configuration of the secondary alcohol, the N was rendered nucleophilic by reduction of the amide to the amine. Oxidation delivered 14, that on activation as the tosylate smoothly rearranged to the ketone 15. Reduction and regioselective dehydration then completed the synthesis of vindoline (1).
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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
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The diol 6 is C 2 -symmetrical, but
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The last challenge was the establis
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(+)-Discodermolide (3), a potent an
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Evans auxiliary-controlled homologa
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39. The Clark Synthesis of Vigulari
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The preparation of 1 began with the
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The preparation of 2 began with Cu-
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With 3 in hand, what remained was a
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44. The Padwa Synthesis of Asphidop
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The aldehyde 1 was in fact not isol
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47. The Nicolaou Synthesis of Plate
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The enantiomercially-pure cyclopent
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Although the tandem ring closing me
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procedure, exposure of the diene 12
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Two such reagents, easily prepared
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The enantiomerically-pure imine 2 w
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Addition of 2-propenyl lithium to t
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The synthesis of 1 started with two
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ing system of vindoline, appropriat
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An additional stereogenic center is
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60. Synthesis of the Potent FBBP12
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The enantiomerically-pure fragments
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Ullman coupling of 3 with the aryl
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Sordaricin (2) is the aglycone of s
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The alcohol 5 was the common interm
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Overall, this elegant synthesis is
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3:1 mixture. That 1 was the major d
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The enantiomerically-pure intermedi
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Deprotection and acid-catalyzed cyc
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72. Total Synthesis of (±)-Sordari
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The ester 2 has a trans 6-5 ring fu
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The enantioselective Cu-catalyzed c
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77. Catalytic Asymmetric Synthesis
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Three-carbon ring expansion was car
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80. Synthesis of (-)-Strychnine The
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The enantiomerically-pure aldehyde
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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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