血管阻断剂活性化合物AVE-8063的合成

A Simple and Efficient Method for the Synthesis of Vascular Disrupting Agent AVE-8063

对血管阻断剂活性分子(Z)-3'-氨基-3,4,4',5-四甲氧基二苯乙烯(AVE-8063)的合成进行了研究。以对甲氧基苯乙酸(Ⅰ)为原料,经溴代及Perkin反应得到(E)-2-(3-溴-4-甲氧基苯基)-3-(3,4,5-三甲氧基苯基)丙烯酸(Ⅲ),再经芳环上溴的氨基取代得到(E)-2-(3-氨基-4-甲氧基苯基)-3-(3,4,5-三甲氧基苯基)丙烯酸(Ⅳ),最后在Cu/1,10-Phen/PEG-400体系微波辅助下反应6 min即脱羧得到目标化合物(Ⅴ),总收率为60.1%。产物结构经IR、MS和1HNMR确证。

A new synthetic protocol leading to the vascular disrupting agent （Z）-3＇-amino-3,4,4＇, 5- tetramethoxylstilbene （ AVE - 8063 ） was successfully devised. Starting from 4-methoxyphenylacetic acid, （E） -2- （ 3-bromo-4-methoxyphenyl ） -3- （ 3,4,5-trimethoxyphenyl ） acrylic acid （ m ） could readily be obtained through bromination and Perkin condensation. Amination of ]U afforded （E）-2-（ 3-animo- 4-methoxyphcnyl）-3-（ 3, 4, 5-trimethoxyphenyl ）acrylic acid （IV）, which was subsequently decarboxylated in Cu/1,10-Phen/PEG-400 system under microwave conditions for 6 rain to give the target product （ V ） with a total yield of 60. 1%. The structure of the product was verified by IR, MS and 1HNMR.