Total Synthesis of Hypermodified Epothilone Analogs with Potent in Vitro Antitumor Activity

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• 作者：Christian N. Kuzniewski ; J&uuml ; rg Gertsch ; Markus Wartmann ; Karl-Heinz Altmann
• 刊名：Organic Letters
• 出版年：2008
• 出版时间：March 20, 2008
• 年：2008
• 卷：10
• 期：6
• 页码：1183 - 1186
• 全文大小：105K
• 年卷期：v.10,no.6(March 20, 2008)
• ISSN：1523-7052

文摘

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The convergent total synthesis of hypermodified epothilone analogs 1 and 2 has been achieved with the stereoselective cyclopropanation ofallylic alcohol 17 and ring-closing olefin metathesis with diene 22 as the key steps. In spite of significant structural differences between theseanalogs and the natural epothilone scaffold, 1 and 2 are potent inducers of tubulin polymerization and inhibit the growth of human cancercells in vitro with sub-nM IC₅₀ values.