8-烯丙基山竹醇的合成及其抗癌活性研究
收稿日期: 2017-01-09
修回日期: 2017-03-25
网络出版日期: 2017-04-10
基金资助
国家自然科学基金（Nos.21272029，81272982）资助项目.
Synthesis and Anticancer Activity of 8-Allyl Garcinol
Received date: 2017-01-09
Revised date: 2017-03-25
Online published: 2017-04-10
Supported by
Project supported by the National Natural Science Foundation of China (Nos. 21272029, 81272982).
山竹醇来源于印度藤黄，具有抗癌和抗炎活性.用烯丙基取代山竹醇结构中C（8）位置上的过大支链5-甲基-2-（1-甲基乙烯基）-4-己烯基，因为这个过大支链可能会影响山竹醇的生物活性和吸收度.以1，3-环己二酮为起始原料，经过Effenburger环化等一系列步骤得到关键桥环中间体（±）-1-羟基-5，5-二甲基-4，6-双（3-甲基-丁-2-烯基）-二环[3.3.1]壬-2-烯-3，9-二酮（8），随后通过五步反应得到8-烯丙基山竹醇，并用噻唑蓝（MTT）法对其进行生物活性测试.研究结果表明，8-烯丙基garcinol对口腔鳞癌细胞具有显著的抑制增殖作用.
关键词： 山竹醇; Effenburger环化; 合成; 结构改造
曹菁 , 韩超明 , 张桂莲 , 周新莹 , 李舒雯 , 杜银端 , 赵帅 , 张辛燕 , 陈新 . 8-烯丙基山竹醇的合成及其抗癌活性研究[J]. 有机化学, 2017 , 37(8) : 2086 -2093 . DOI: 10.6023/cjoc201701017
Garcinol, isolated from the fruit rind of Garcinia indica, shows anti-carcinogenic and anti-inflammatory activities. However, the C(8) side chain of garcinol is so large that it may influence the bioactivity of the compound. 8-Allyl garcinol, in which the bulky side chain at C(8) position of garcinol is replaced with much smaller allyl group, was synthesized through a 12-step procedure. Starting from 1,3-cyclohexandione, the key intermediate (±)-1-hydroxy-5,5-dimethyl-4,6-bis(3-methylbut-2-en-1-yl)bicyclo[3.3.1]non-2-ene-3,9-dione (8) was obtained via Effenburger cyclization. Through additional 5-steps, 8-allyl garcinol was prepared. The thiazolyl blue tetrazolium bromide (MTT) results indicated that 8-allyl garcinol shows strong inhibitory activity on cell proliferation of oral cancer cell lines.
Key words： garcinol; Effenburger cyclization; synthesis; structural modification
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