有机化学 ›› 2017, Vol. 37 ›› Issue (8): 2086-2093.DOI: 10.6023/cjoc201701017 上一篇    下一篇

研究论文

8-烯丙基山竹醇的合成及其抗癌活性研究

曹菁a, 韩超明a, 张桂莲b, 周新莹b, 李舒雯a, 杜银端a, 赵帅a, 张辛燕b, 陈新a   

  1. a 常州大学制药与生命科学学院 常州 213164;
    b 首都医科大学附属北京口腔医院 口腔医学研究所 北京 100050
  • 收稿日期:2017-01-09 修回日期:2017-03-25 出版日期:2017-08-25 发布日期:2017-04-10
  • 通讯作者: 张辛燕, 陈新 E-mail:xinyanzhangzh@126.com;xinchen@cczu.edu.cn
  • 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

Cao Jinga, Han Chaominga, Zhang Guilianb, Zhou Xinyingb, Li Shuwena, Du Yinduana, Zhao Shuaia, Zhang Xinyanb, Chen Xina   

  1. a School of Pharmaceutical Engineering and Life Science, Changzhou University, Changzhou 213164;
    b Beijing Institute of Dental Research, Beijing Stomatological Hospital, Capital Medical University, Beijing 100050
  • Received:2017-01-09 Revised:2017-03-25 Online:2017-08-25 Published:2017-04-10
  • Contact: 10.6023/cjoc201701017 E-mail:xinyanzhangzh@126.com;xinchen@cczu.edu.cn
  • 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

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