Total Synthesis Highlights

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The elegantly concise strategy displayed here for the enantioselective and diastereoselective construction of the tricyclic enone 3, by two-directional tandem methathesis of the Diels-Alder derived diketone 1, should have some generality 67. Enantioselective <strong>Synthesis</strong> of (-)-Epoxomycin For many classes of physiologically-important natural products, total synthesis requires the construction of an extended array of acyclic stereogenic centers, with control of relative and absolute configuration. In the course of a synthesis (J. Am. Chem. Soc. 2004, 126, 15348.) of the proteasome inhibitor (-)-epoxomycin (3), Lawrence J. Williams of Rutgers University has developed an elegant and potentially powerful solution to this problem. It was apparent that the preparation of 3 reduced to the stereocontrolled synthesis of 2, since the balance of the natural product is made up of readily-available amino acids. The oxygenated quaternary center of 2 appeared to be a particular challenge. The key insight of the synthesis was that both centers could be established in a single step by selective nucelophilic opening of the enantiomerically-enriched spiro bis epoxide 1. The left hand fragment of epoxymycin 3 was assembled from the previously-described amino acid derivatives 4, 5, and 7, using standard coupling techniques. The preparation of the allene bis-epoxide 1 started with isovaleraldehyde 9. Addition of the protected propargyl alcohol 10 under the Carreira conditions led to 11 in > 95% ee. Mesylation followed by displacement with methyl cuprate provided the allene without loss of enantiomeric excess. Oxidation of the allene 12 with dimethyldioxirane could have led to any of the four diastereomers of the spiro bis epoxide. In the event, only two diastereomers were observed, as a
3:1 mixture. That 1 was the major diastereomer followed from its conversion to 3. The configuration of the minor diastereromer was not noted. Exposure of 1 to nucleophilic azide then gave the easily-purified 2. The spirodiepoxide 1 is an intriguing new approach to relative and absolute stereocontrol. It will be interesting to see what other nucleophiles can be used in the opening. It is possible that a chiral oxygen transfer reagent, such as the dioxirane prepared by the Shi protocol, would convert 12 to 1 with improved diastereoselectivity (double diastereoselection) 68. Enantioselective <strong>Synthesis</strong> of the Polyene Antiobiotic Aglycone Rimocidinolide Methyl Ester The complex polyene macrolide antibiotics are clinically effective as antifungal agents. Scott Rychnovsky of the University of California at Irvine has reported (Angew. Chem. Int. Ed. 2004, 43, 2822. ) the first synthesis of rimocidinolide methyl ester (4), the aglycone of rimocidin (1). The key step in the synthesis is the condensation of the aldehyde 2 with the phosphonate 3, leading to 4. Preparation of the Aldehyde 2: The absolute configuration of the triene aldehyde 2 was set by Noyori hydrogenation of ethyl butyrylacetate 5. Silylation and Dibal reduction then gave the aldehyde 6. Reduction of the homologated ester gave the alcohol, which was oxidized to the
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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
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 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: Overall, this elegant synthesis is
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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