A Second-Generation Synthesis of the C1-C28 Portion of the Altohyrtins (Spongistatins)

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• 作者：Jed L. Hubbs and Clayton H. Heathcock
• 刊名：Journal of the American Chemical Society
• 出版年：2003
• 出版时间：October 22, 2003
• 年：2003
• 卷：125
• 期：42
• 页码：12836 - 12843
• 全文大小：174K
• 年卷期：v.125,no.42(October 22, 2003)
• ISSN：1520-5126

文摘

A practical second-generation synthesis of an advanced intermediate in our total synthesis ofaltohyrtin C (spongistatin 2) has been developed. A new approach to the C1-C15 (AB) portion features avinyllithium addition to an aldehyde followed by a palladium-catalyzed allylic reduction to install thetroublesome C13-C15 segment. Our general approach to the C16-C28 (CD) spiroketal has been retained,but some improvements have been made. Most notably, the kinetically controlled CD-spiroketalizationreaction now proceeds in high yield with excellent diastereoselection. This new strategy uses the anti-aldol coupling used in our first-generation synthesis to join AB and CD fragments. A total of 9.6 g ofintermediate 57 has been produced using this improved route.