A second-generation synthesis of the C1-C28 portion of the altohyrtins (spongistatins)

被引：57

作者：

Hubbs, JL ^{[1
]}

Heathcock, CH ^{[1
]}

机构：

[1] Univ Calif Berkeley, Ctr New Direct Organ Synth, Dept Chem, Berkeley, CA 94720 USA

来源：

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY | 2003年 / 125卷 / 42期

关键词：

D O I：

10.1021/ja030316h

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

A practical second-generation synthesis of an advanced intermediate in our total synthesis of altohyrtin C (spongistatin 2) has been developed. A new approach to the C1 -C15 (AB) portion features a vinyllithium addition to an aldehyde followed by a palladium-catalyzed allylic reduction to install the troublesome 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-spiroketalization reaction 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 of intermediate 57 has been produced using this improved route.

引用

页码：12836 / 12843

页数：8

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