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有机化学
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有机化学 ›› 2006, Vol. 26 ›› Issue (9): 1221-1224. 上一篇    下一篇

研究论文

10-酯基高喜树碱的全合成及抗肿瘤活性研究

缪震元，张万年*，姚建忠，盛春泉，徐辉
张珉，张晶，游亮，车晓颖   

  1. (中国人民解放军第二军医大学药学院 上海 200433)
  • 收稿日期:2005-12-06 修回日期:1900-01-01 发布日期:2006-09-11
  • 通讯作者: 张万年

Synthesis and Antitumor Activity of 10-Ester Derivatives of Homocamptothecin

MIAO Zhen-Yuan,ZHANG Wan-Nian*,YAO Jian-Zhong,SHENG Chun-Quan
XU Hui,ZHANG Min,ZHANG Jing,YOU Liang,CHE Xiao-Ying   

  1. (School of Pharmacy, Second Military Medical University of the People’s Liberation Army of China, Shanghai 200433)
  • Received:2005-12-06 Revised:1900-01-01 Published:2006-09-11
  • Contact: ZHANG Wan-Nian

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1015

被引次数

5

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1H NMR, 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.

关键词: 10-酯基高喜树碱, 全合成, 抗肿瘤活性

omocamptothecin 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.

Key words: total synthesis, antitumor activity, 10-ester-homocamptothecin