Catharanthine C16 substituent effects on the biomimetic coupling with vindoline: Preparation and evaluation of a key series of vinblastine analogues

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• 作者：Annie Tam ; Hiroaki Gotoh ; William M. Robertson ; Dale L. Boger
• 关键词：Vinblastine ; Catharanthine ; Vindoline
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2010
• 出版时间：15 November 2010
• 年：2010
• 卷：20
• 期：22
• 页码：6408-6410
• 全文大小：336 K

文摘

The examination of the catharanthine C16 substituent effects on the Fe(III)-promoted biomimetic coupling reaction with vindoline is detailed, confirming the importance of the presence of a C16 electron-withdrawing substituent, and establishing an unanticipated unique role (>10-fold) that the C16 methyl ester plays in the expression of the natural product properties. Thus, replacement of the vinblastine C16′ methyl ester with an ethyl ester (10-fold), a cyano group (100-fold), an aldehyde (100-fold), a hydroxymethyl group (1000-fold) or a primary carboxamide (>1000-fold) led to surprisingly large reductions in cytotoxic activity.