10-酯基高喜树碱的全合成及抗肿瘤活性研究  

Synthesis and Antitumor Activity of 10-Ester Derivatives of Homocamptothecin

作　　者：缪震元[1] 张万年[1] 姚建忠[1] 盛春泉[1] 徐辉[1] 张珉[1] 张晶[1] 游亮[1] 车晓颖[1] 

机构地区：[1]中国人民解放军第二军医大学药学院,上海200433

出　　处：《有机化学》2006年第9期1221-1224,共4页Chinese Journal of Organic Chemistry

基　　金：国家自然科学基金(No.30371689)资助项目.

摘　　要：以2,8-二氧-3-乙基-6,6-亚乙二氧基-2,3,5,6,7,8-六氢-3-羟基吡喃(5,4-c)中氮茚为起始原料,经五步反应得到高喜树碱,羟甲基化后与一系列酸成酯合成了6个10-酯基高喜树碱,并利用1HNMR,MS及元素分析对其结构进行了表征.采用经典的噻唑兰(Thiazoly blue tetrazolium bromide,MTT)法测定了其体外抗肿瘤活性,活性测试结果表明3个化合物具有比阳性对照药拓扑替康增强的活性.Homocamptothecin was prepared by a novel total synthetic method in five steps from the tricyclic starting material 2,8-dioxo-3-ethyl-6,6-ethylenedioxy-2,3,5,6,7,8-hexahydro-3-hydroxypyrano（5,4- c）indolizine. Hydrogen peroxide oxidized homocamptothecin with methanol to form 10-hydroxymethyl- homocamptothecin, which then reacted with a series of acids to afford six 10-ester derivatives of homocamptothecin. Their structures were characterized by ^1H NMR, MS spectra and elemental analysis. Antitumor activity tests in vitro by MTT method indicated that three compounds possessed higher inhibiting activity against A-549, LOVO and MCF-7 cell lines than topotecan.

关 键 词：10-酯基高喜树碱 全合成 抗肿瘤活性 

分 类 号：R914[医药卫生—药物化学] R73-3[医药卫生—药学]