Total Synthesis Highlights

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The cyclization of 2 to 11 proceeded smoothly, as did the alkylation of 11 to 12. The diastereoselectivity of the alkylation followed from the conformational bias of the ring system. The conversion of the terminal alkene to the acid 13 initially was troublesome, but a solution was found in metathesis with vinyl boronate followed by oxidation. Coupling with 11 followed by deprotection then gave 3. The absolute configuration of the tricyclic core of 3 was set in the intramolecular ene cyclization of 6 to 7. There is the possibility that with an enantiomerically-pure catalyst, the product 7 and so 3 could be prepared in high enantiomeric excess. <strong>Total</strong> syntheses of platensimycin 3 are underway in several other research groups. The diversity of the approaches being explored will enrich organic synthesis. 48. The Sorensen <strong>Synthesis</strong> of (-)-Guanacastepene E The guanacastepenes, of which guanacastepene E (3) is representative, initially elicited excitement because of their activity against drug resistant bacterial strains. Although the systemic toxicity of the guanacastepenes has cooled that enthusiasm, the guanacastepenes remain as architectural challenges. In particular, a convergent synthesis plan requires the development of a strategy for constructing the central 7-membered ring with control of relative and absolute configuration, particularly of the two angularly methylated quaternary centers. Erik J. Sorensen of Princeton University (J. Am. Chem. Soc. 2006, 128, 7025.) solved this problem by the intramolecular photochemical dimerization of 1, which delivered 2 with high diastereocontrol. Directed ring fragmentation then led to 3.
The enantiomercially-pure cyclopentenone of 1 was prepared from the chiral pool starting material dihydrocarvone (4). Methylation followed by ozonolytic cleavage gave the aldehyde acid 5, which was converted into the cyanohydrin lactone 6. Intramolecular acylation of the derived nitrile anion proceeded smoothly, to give, after fragmentation, the 1,2-diketone 7. Stannylation of the nonaflate led to 8, which was coupled with enantiomerically-pure 9 to give 1. Construction of the cyclohexene 9 began with the Diels-Alder cycloaddition of the alkyne 11 to the diene 10, followed by Baeyer-Villiger cleavage to give 13. This established the quaternary center, and at the same time set the relative configuration of the secondary alcohol of 9, and thus of 3. The alcohol 15 so prepared was racemic. Screening of esters led to the mandelate acetate 9, the diastereomers of which could be separated by open column chromatography. The mandelate ester also proved to be an effective leaving group for the Pd-mediated coupling of 8 and 9 to give 1. As anticipated, the intramolecular 2+2 photocyclization was directed by the adjacent isopropyl group, to give 2 with high diastereocontrol. While opening of carbonyl-activated fused cyclopropanes is amply precedented, far less was known about the opening of carbonyl-activated fused cyclobutanes. Happily, double one-electron reduction with excess SmI 2 opened the desired bond, to give, after selenation and oxidation, the dienenone 16. The acetoxy group adjacent to the ketone was introduced by Rubottom oxidation. On deprotection of 17, the released primary alcohol spontaneously added to the enone, to give (-)-guanacastepene E (3) .
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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
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 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: 47. The Nicolaou Synthesis of Plate
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 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
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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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