抗癌药物Combretastatin A-4及其水溶性衍生物的合成

Synthesis of combretastatin A-4 and its water-soluble analogues

目的:合成抗癌药物Combretastatin A-4及其水溶性衍生物。方法:以三甲氧基苯乙酸与异香兰素为原料,经缩合或进一步连接侧链、脱羧等反应合成Combretastatin A-4及其水溶性衍生物。结果:目标化合物经核磁共振氢谱、碳谱、质谱、熔点等确证其化学结构,总收率均达到40%左右。结论:该路线反应条件简便,步骤较短,对顺式产物选择性高,适合工业化生产。

Objective： To synthesize the anticancer agent combretastatin A-4 and its water-soluble analogues. Methods： 3,4,5-Trimethoxyphenylacetic acid and isovanilline were used as starting materials to prepare combretastatin A-4 and its water-soluble analogues via condensation, modification with mPEG side chain, and decarboxylation reactions. Results： The structures of target compounds were confirmed by ^1H NMR,^13C NMR, MS and melting point; the overall yields were about 40%. Conclusion： The synthetic routes developed herein require simple reaction conditions and few steps, and yield high stereoselectivity of cis conformation, which are suitable for large-scale manufacturing.