海绵抑素（altohyrtins）C1 - C28部分的第二代合成。

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

作者信息

Hubbs Jed L, Heathcock Clayton H

机构信息

Center for New Directions in Organic Synthesis, Department of Chemistry, University of California, Berkeley, California 94720, USA.

出版信息

J Am Chem Soc. 2003 Oct 22;125(42):12836-43. doi: 10.1021/ja030316h.

DOI:10.1021/ja030316h

PMID:14558832

Abstract

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.

摘要

已开发出一种实用的第二代合成方法，用于我们全合成阿托海汀C（海绵他汀2）中的一种高级中间体。一种合成C1-C15（AB）部分的新方法的特点是，向醛中加入乙烯基锂，然后进行钯催化的烯丙基还原，以安装棘手的C13-C15片段。我们合成C16-C28（CD）螺缩酮的一般方法得以保留，但也进行了一些改进。最显著的是，动力学控制的CD-螺缩酮化反应现在以高收率和优异的非对映选择性进行。这种新策略使用了我们第一代合成中使用的反羟醛缩合反应来连接AB和CD片段。使用这种改进的路线总共制备了9.6 g中间体57。