Total Synthesis Highlights

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Although one might think of medium rings such as that of 2 as being floppy, in fact 2 has a single preferred conformation, and diastereocontrol for the rest of the synthesis took advantage of that preferred conformation. The diene 11 derived from 2 has one open face. Addition of methyl vinyl ketone to that outside face gave a 1 : 2 mixture of the diastereomeric endo and exo cycloadducts. The mixture was equilibrated to the more stable exo adduct 12. A four-step sequence then converted 12 into 13. The completion of the synthesis again depended on the inside-outside bias of the medium ring. Addition of methyl magnesium chloride to the outside face of the ketone derived from 13 delivered 14 with high diastereocontrol. Epoxidation of 14, again from the outside face, led directly to vigulariol 3. The intermediate in the MCPBA reaction is the protonated epoxide, and it may be that the tertiary alcohol poised directly on the opposite face of the alkene opened that activated intermediate directly. This synthesis of vigulariol (3) is remarkably concise, with four rings and eight stereogenic centers being assembled in just twenty steps. All of the stereogenic centers are derived from the secondary alcohol 6. Use of the known enantiomerically-pure 6 would have delivered vigulariol (3) in enantiomerically-pure form. This synthesis design once again illustrates the power of conformational analysis of medium rings. 40. The Trost <strong>Synthesis</strong> of (-)-Terpestacin (-)-Terpestacin (3), isolated from Arthrinium sp. FA1744, inhibits the formation of syncytia by HIV-infected T cells. A key step in the total synthesis of 3 reported (J. Am. Chem. Soc. 2007, 129, 4540. ) by Barry M. Trost of Stanford University was the Ru-catalyzed cyclization of 1 to 2. This synthesis of (-)-terpestacin (3) elegantly illustrates the power of the Trost enantioselective Pd catalysts.
The preparation of 1 began with the commercially-available diketone 4. With the enol as the nucleophile, opening of racemic isoprene monoepoxide 5 using the Trost chiral Pd catalyst led to the ether 6 in high ee. It is impressive that even though it was directed by a quaternary stereogenic center, the subsequent Claisen rearrangement to 7 proceeded with complete facial selectivity. Oxidation to the nonenolizable α-diketone 8 then set the stage for the conjugate addition. Again, even though the directing stereogenic center was quaternary, the addition proceeded with substantial diastereocontrol. Further study of the elements that govern the facial selectivity of the Lewis acid-mediated (Sakurai) addition of allyl silanes to enones would certainly be warranted. The sulfone 11 was prepared in four steps from commericially-available geranyl bromide, with the absolute configuration being set by Sharpless asymmetric epoxidation. Subsequent to the alkylation of 11 with the bromide 10, the now-surplus sulfone was removed reductively with Pd(OAc) 2 and NaBH 4 . It is noteworthy that the enone of 1 was stable to those conditions. The cyclization of 1 with the second-generation Grubbs catalyst delivered the desired E alkene 2 in 43% yield. As had been observed before by others, the free allylic alcohol was the preferred substrate for the Ru metathesis catalyst. No cyclization was observed with tetraenes that had the alcohol protected. With 2 in hand, it remained to install the side chain. The relative configuration of the pentenyl side chain of 14 was set by again using chiral Pd catalysis. The Claisen rearrangement proceeded smoothly, to give, after protection, the ether 15.
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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
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
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: 39. The Clark Synthesis of Vigulari
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
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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
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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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