Relative Stereochemical Determination and Synthesis of the C17鈥揅25 未-Lactone Fragment of Hemicalide

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• 作者：Etienne Fleury ; Geoffroy Sorin ; Elise Prost ; Ange Pancrazi ; Fran莽ois Sautel ; Georges Massiot ; Marie-Isabelle Lannou ; Janick Ardisson
• 刊名：The Journal of Organic Chemistry
• 出版年：2013
• 出版时间：February 1, 2013
• 年：2013
• 卷：78
• 期：3
• 页码：855-864
• 全文大小：533K
• 年卷期：v.78,no.3(February 1, 2013)
• ISSN：1520-6904

文摘

Hemicalide is a novel marine metabolite polyketide distinguished by a unique mechanism of action. Because of insufficient quantities of purified material, this natural product has evaded complete stereochemical assignments. Recently, we have determined the relative stereochemistry of the C8鈥揅13 hexad by synthesizing the C1鈥揅13 fragment. Presently, we report the assignment of the C17鈥揅25 未-lactone fragment. NMR analysis of authentic hemicalide along with a computational conformation study allowed us to reduce the number of putative relative isomers from 16 to 4. Concise syntheses of the four candidate diastereomers were achieved using a common strategy based on a Dias aldehyde allylation reaction, an intramolecular Horner鈥揥adsworth鈥揈mmons olefination, and a dihydroxylation reaction. Finally, thorough NMR comparisons enabled us to deduce the relative stereochemistry of the C1鈥揅17 fragment with high certainty.