A Practical Entry to the Crambescidin Family of Guanidine Alkaloids. Enantioselective Total Syntheses of Ptilomycalin A, Crambescidin 657 and Its Methyl Ester (Neofolitispates 2), and Crambescidin 800

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• 作者：D. Scott Coffey ; Andrew I. McDonald ; Larry E. Overman ; Michael H. Rabinowitz ; and Paul A. Renhowe
• 刊名：Journal of the American Chemical Society
• 出版年：2000
• 出版时间：May 24, 2000
• 年：2000
• 卷：122
• 期：20
• 页码：4893 - 4903
• 全文大小：503K
• 年卷期：v.122,no.20(May 24, 2000)
• ISSN：1520-5126

文摘

Among the most structurally remarkable guanidine natural products are the crambescidin/ptilomycalinA family of marine alkaloids. The evolution of a practical strategy for preparing pharmacologically significantcrambescidin/ptilomycalin A alkaloids that lack oxidation at C13 is described. The first total syntheses ofcrambescidin 800 (2), crambescidin 657 (6), and neofolitispate 2 (7) are reported in full detail. The centralstrategic step in these convergent total syntheses is tethered Biginelli condensation of -keto ester 24 withureido aminal 61 to combine all carbons of the guanidine nucleus and set the pivotal C10-C13 stereorelationship.The total synthesis of crambescidin 800 (2) was accomplished in 3% overall yield from commercially available3-butyn-1-ol by way of 16 isolated and purified intermediates. Full details of our earlier total synthesis ofptilomycalin A (1) are also presented. The total syntheses described in this disclosure confirm the stereochemicalassignments of 1, 2, 6, and 7 and rigorously establish that the absolute configuration of the hydroxyspermidineside chain of crambescidin 800 (2) is S.