7-氧杂双环[2.2.1]庚-2,3-二甲酸衍生物的合成及其抗HIV活性

Synthesis of 7-Oxabicyclo[2.2.1]heptane-2,3-dicarboxylic Acid Derivatives and Their anti-HIV Activity

以呋喃和顺丁烯二酸酐为原料,经环化反应制得7-氧杂双环[2.2.1]庚-5-烯-2,3-二甲酸酐(3);打开3的酸酐五元环,选择性地进行单酯化反应,合成了一系列7-氧杂双环[2.2.1]庚-3-烷氧羰基-2-甲酸(4a～4d),其结构经1H NMR和MS表征。初步探讨了4的抗HIV构效关系,其中4a的治疗指数与其先导化合物去甲基斑蝥素相当,毒性较之降低。

A series of 7-oxabicyclo [ 2.2. 1 ] heptane-3-alkoxyl-carbonyl-2-dicarboxylic acids （ 4a - 4d） were synthesized by selective single esterification from 7-oxabicyclo[2.2.1] heptane-5-ene-2,3- dicarboxylic acid which was prepared by eyclization from furan and maleic anhydride. The structures were characterized by ^1H NMR and MS. anti-HIV-1 activity of 4 and norcantharidin（the parent compound of 4） are evaluated and the structure activity relationship of 4 is discussed. The results show that the therapeutic index of 4a is the same as that of norcantharidin, and the toxity of 4a is lower than that of norcantharidin.