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Synthesis 2011(2): 217-222  
DOI: 10.1055/s-0030-1258358
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

Practical and Green Synthesis of Combretastatin A-4 and Its Prodrug CA4P Using Renewable Biomass-Based Starting Materials

Yu Chena,b, Yong Zou*a, Hong-Yi Suna,b, Xian-Ke Liua,b, Chun-Fen Xiaoa,b, Jie Suna,b, Shu-Jie Hea, Jun Li*c
a Guangzhou Institute of Chemistry, Chinese Academy of Sciences, Guangzhou 510650, P. R. of China
Fax: +86(21)85231119; e-Mail: zou_jinan@163.com;
b Graduate School of Chinese Academy of Sciences, Beijing 100039, P. R. of China
c Second Affiliated Hospital, College of Medicine, Zhejiang University, Zhejiang 310009, P. R. of China
Further Information

Publication History

Received 13 September 2010
Publication Date:
08 December 2010 (online)

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Abstract

A practical and green protocol for the synthesis of vascular disrupting agent combretastatin A-4 (CA4) and its water soluble prodrug CA4P is described. Starting from the biomass-based compound anethole, which is abundantly and sustainably available from Chinese star anise (Illicium verum Hook. f.), the key intermediate 3-hydroxy-4-methoxyphenylacetic acid can be obtained within five steps. Perkin condensation between this acid and another naturally derived compound 3,4,5-trimethoxybenzaldehyde, followed by decarboxylation gives combretastatin A-4 in good overall yield. The phosphate produrg CA4P can be prepared under simple and mild conditions in a sequential one-pot two-step reaction.

Key words

combretastatin A-4 - combretastatin A-4 phosphate - renewable sources - green synthesis - Perkin reaction

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The crystallographic data (excluding structure factors) for (NH4)2SO4˙MnSO4˙6H2O have been deposited at FIZ Karlsruhe as supplementary publication number CSD: 422123. Copies of the data can be obtained free of charge on application to FIZ Karlsruhe, Hermann-von-Helmholtz-Platz 1, 76344 Eggenstein-Leopoldshafen, Germany [fax: +49(7247)808259; e-mail: crysdata@fiz-karlsruhe.de].