Novel syntheses of cis and trans isomers of combretastatin A-4

被引：167

作者：

Gaukroger, K

Hadfield, JA ^{[1
]}

Hepworth, LA

Lawrence, NJ

McGown, AT

机构：

[1] Christie Hosp NHS Trust, Paterson Inst Canc Res, CRC, Drug Dev Grp, Manchester M20 4BX, Lancs, England

[2] Christie Hosp NHS Trust, Paterson Inst Canc Res, CRC, Radiochem Targeting & Imaging Grp, Manchester M20 4BX, Lancs, England

[3] UMIST, Dept Chem, Manchester M60 1QD, Lancs, England

[4] Cardiff Univ, Dept Chem, Cardiff CF10 3TB, S Glam, Wales

[5] Univ Salford, Dept Chem, Ctr Mol Drug Design, Salford M5 4WT, Lancs, England

来源：

JOURNAL OF ORGANIC CHEMISTRY | 2001年 / 66卷 / 24期

关键词：

D O I：

10.1021/jo015959z

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

A high-yielding, two-step stereoselective synthesis of the anticancer drug (Z)-combretastatin A-4 (1) has been devised. The method uses the Perkin condensation of 3,4,5-trimethoxyphenylacetic acid and 3-hydroxy-4-methoxybenzaldehyde followed by decarboxylation of the cinnamic acid intermediate using copper and quinoline. The iodine-catalyzed isomerization of the Z isomer 1 results in complete conversion to the E isomer. The Suzuki cross-coupling of an aryl boronic acid and vinyl bromide has also been successfully employed to produce both Z and E isomers of combretastatin A-4 stereoselectively. Both methods are far superior to the current five-step Wittig synthesis in which both isomers are produced nonstereoselectively.

引用

页码：8135 / 8138

页数：4

共 37 条

[1] THE PALLADIUM-CATALYZED CROSS-COUPLING REACTION OF ENOL ACETATES OF ALPHA-BROMO KETONES WITH 1-ALKENYLBORON, ARYLBORON, OR ALKYLBORON COMPOUNDS - A FACILE SYNTHESIS OF KETONES AND THEIR ENOL ACETATES [J].