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

摘要:

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分钟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1H NMR确证。

Abstract:

A new synthetic protocol leading to 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 (Ⅲ) could readily be obtained through bromination and Perkin condensation. Amination of (Ⅲ) afforded (E)-2-(3-animo-4-methoxyphenyl)-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 min to give the target product (Ⅴ) with 60.1% total yield. The structure of the product was verified by IR, MS and 1H NMR.