The Knight route to cyclopiazonic acid: enantioselective synthesis of a key intermediate

被引：11

作者：

Beyer, Christian ^{[1
]}

Scherkenbeck, Juergen ^{[1
]}

Sondermann, Frank ^{[1
]}

Figge, Axel ^{[1
]}

机构：

[1] Berg Univ Wuppertal, Fachgrp Chem, D-42119 Wuppertal, Germany

来源：

TETRAHEDRON | 2010年 / 66卷 / 35期

关键词：

Indole alkaloid; Cylopiazonic acid; SERCA; Key-intermediate; Enantioselective synthesis; Evans auxiliary; AZIRIDINATION; CA2+-ATPASE; CHEMISTRY;

D O I：

10.1016/j.tet.2010.06.092

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

The indole alkaloid alpha-cyclopiazonic acid (CPA) is one of the few known inhibitors of sarco(endo) plasmic reticulum Ca(2+)-ATPase (SERCA) besides thapsigargin and artemisinin. Inhibitors of SERCA hold promise as novel anticancer and antimalarial drugs. Since its structure elucidation three racemic syntheses of alpha-cyclopiazonic acid have been published. We report now the first enantioselective and high yielding synthesis of a key-intermediate of the Knight synthesis, currently the most efficient route to CPA. Our synthesis is based on a diastereoselective 1,4-cuprate addition followed by an enolate azidation of an indolylacrylic acid modified with the Evans auxiliary. (C) 2010 Elsevier Ltd. All rights reserved.

引用

页码：7119 / 7123

页数：5

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