Total Synthesis Highlights

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Conjugate addition to 1 proceeded across the open face of the bicyclic system to give an enolate, condensation of which with the enantiomerically-pure aldehyde 8 gave the enone 9. Conjugate reduction of the enone also removed the benzyl ether, to give the alcohol. Conversion of the alcohol to the azide gave 10. Ozonolysis followed by selective reduction then gave 2. The acid-mediated intramolecular addition of the azide to the ketone proceeds by way of addition followed by a pinacol-type rearrangement, to give the amide 12. The regioselectivity of the bond migration is remarkable. Reduction of the amide then gave 3. 75. Enantioselective <strong>Synthesis</strong> of (+)-Tricycloclavulone Triclavulone 3, recently isolated from Clavularia vulgaris, is one of the most complex of the family of about forty structurally-related fatty acid-derived marine prostanoids described from this species. Hisanaka Ito and Kazuo Iguchi of the Tokyo University of Pharmacy and Life Science recently reported (J. Am. Chem. Soc. 2004, 126, 4520. ) the total synthesis of 3, starting with the preparation of the enantiomerically-enriched bicyclic ketone 1.
The enantioselective Cu-catalyzed cycloaddition of the reactive enone 4 to the alkyne 5 proceeded efficiently, but with only modest enantiomeric excess. This was improved at a later point in the synthesis, by recrystallization of 2. The folded geometry of 1 directed the Grignard addition, to give, after protection, the ester 7. Homologation to the allylic alcohol 8 set the stage for Grubbs ring closure, to give, after oxidation, the tricyclic sulfone 9, having the skeleton of triclavulone 3. There were two more stereocenters to set. It was expected that cuprates would add to the open face of the strained cyclobutene. The control of the other stereocenter was more problematic. One solution was to prepare an α-sulfonyl lactone. To this end, the ketone was converted to the secondary carbonate. As hoped, conjugate addition was followed by intramolecular acylation, but the reaction continued to full acyl transfer, to give 10. Fortunately, desilylation of 10 proceeded with concomitant lactonization. Desulfonylation then gave 2, which could be brought to high ee by recrystallization. With 2 in hand, the rest of the synthesis proceeded smoothly. Reprotection followed by reduction and oxidation gave the keto aldehyde 11. Condensation of the keto phosphonate 12 with 11 gave the enone 13. Enantioselective transfer hydrogenation of 13 gave the allylic alcohol 14 with 11:1 diastereoselectivity. Protecting group interchange then gave triclavulone 3, identical in every respect with natural material.
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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
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The Hoveyda Synthesis of (-)-Clavir
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eduction of 8 delivered the primary
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The seemingly simple task of conver
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fermentation of halogenated aromati
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The octaene 1 was assembled from fo
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The starting point for the preparat
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Several aspects of this synthesis a
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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
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: The ester 2 has a trans 6-5 ring fu
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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