有机化学 ›› 2017, Vol. 37 ›› Issue (1): 133-140.DOI: 10.6023/cjoc201608002 上一篇    下一篇

研究论文

新型槲皮素缀合物的合成与降糖活性研究

潘国军a, 肖娜b, 沈棣a, 陈明朗a, 李屹b, 芦逵a, 杨杨a, 孟欣a, 郁彭a   

  1. a 天津科技大学生物工程学院 天津 300457;
    b 中国药科大学中药学院 南京 210000
  • 收稿日期:2016-08-02 修回日期:2016-09-05 出版日期:2017-01-25 发布日期:2016-09-12
  • 通讯作者: 孟欣, 郁彭 E-mail:mengxin@tust.edu.cn;yupeng@tust.edu.cn
  • 基金资助:

    国家自然科学基金(Nos. 21502139,21402140)及天津市科技特派员(No. 15JCTPJC56200)资助项目.

Synthesis and Hypoglycemic Activity of Novel Quercetin Conjugates

Pan Guojuna, Xiao Nab, Shen Dia, Chen Minglanga, Li Yib, Lu Kuia, Yang Yanga, Meng Xina, Yu Penga   

  1. a College of Technology, Tianjin University of Science and Technology, Tianjin 300457;
    b College of Traditional Chinese Medicine, China Pharmaceutical University, Nanjing 210000
  • Received:2016-08-02 Revised:2016-09-05 Online:2017-01-25 Published:2016-09-12
  • Supported by:

    Project supported by the National Natural Science Foundation of China(Nos. 21502139, 21402140) and the Science and Technology Commissioner Foundation of Tianjin(No. 15JCTPJC56200).

经过五步反应以15%~46%的总收率成功合成了8个新型的槲皮素缀合物20~27.以芦丁为起始原料,经O-苄基化、酸催化糖苷水解、烷基化等步骤,获得重要中间体5,7,3',4'-四苄氧基-3-O-炔丙基槲皮素;再经过Click反应,得到槲皮素缀合物中间体12~19,最后经催化氢化得到系列糖基、聚乙二醇(PEG)或寡聚乙二醇(OEG)与槲皮素偶联的新型缀合物.经体外3T3-L1脂肪细胞水平降糖活性测试,结果显示缀合物24,2627具有较好的降糖活性.

关键词: 槲皮素缀合物, Click反应, 合成, 降糖活性, 脂肪细胞

Eight novel quercetin conjugates 20~27 were successfully synthesized through a concise procedure with 15%~46% overall yields by using Rutin as the starting material.After O-benzylation,glycoside hydrolysis and O-propargylation,rutin was converted to the key intermediate 5,7,3',4'-tetrabenzyloxy-3-O-propargylquercetin,which subsequently ‘clicked’ with azido containing glycosides,poly(ethylene glycol)(PEG) or oligo(ethylene glycol)(OEG) to provide the fully protected quercetin conjugates 12~19.After global deprotection,the resulting quercetin conjugates were evaluated on hypoglycemic activities at 3T3-L1 adipocyte level.The results showed that conjugates 24,26 and 27 exhibited good hypoglycemic effects.

Key words: quercetin conjugate, click reaction, synthesis, hypoglycemic activity, adipocyte