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

Gaukroger, K; Hadfield, JA; Hepworth, LA; Lawrence, NJ; McGown, AT

Abstract

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.

Citation

Gaukroger, K., Hadfield, J., Hepworth, L., Lawrence, N., & McGown, A. (2001). Novel syntheses of cis and trans isomers of combretastatin A-4. Journal of Organic Chemistry, 66(24), 8135-8138. https://doi.org/10.1021/jo015959z

• Journal Article Type: Article
• Publication Date: Nov 2, 2001
• Deposit Date: Aug 7, 2007
• Journal: Journal of Organic Chemistry
• Print ISSN: 0022-3263
• Publisher: American Chemical Society
• Peer Reviewed: Peer Reviewed
• Volume: 66
• Issue: 24
• Pages: 8135-8138
• DOI: https://doi.org/10.1021/jo015959z
• Publisher URL: http://dx.doi.org/10.1021/jo015959z