Chinese Journal of Organic Chemistry ›› 2021, Vol. 41 ›› Issue (9): 3643-3651.DOI: 10.6023/cjoc202105003 Previous Articles     Next Articles



李丰兴, 卢昕, 刘旭, 苏路路, 李小六, 陈华*   

  1. 河北大学化学与环境科学学院 河北省化学生物学重点实验室 河北保定 071002
  • 收稿日期:2021-05-02 修回日期:2021-05-31 发布日期:2021-06-22
  • 通讯作者: 陈华
  • 基金资助:
    国家自然科学基金(21772031); 河北省自然科学基金(B2019201398)

Structural Modification of Benzimidazole-Iminosugars and Their Inhibitory Activities against β-Glycosidases

Fengxing Li, Xin Lu, Xu Liu, Lulu Su, Xiaoliu Li, Hua Chen   

  1. Key Laboratory of Chemical Biology of Hebei Province, College of Chemistry and Environmental Science, Hebei University, Baoding, Hebei 071002
  • Received:2021-05-02 Revised:2021-05-31 Published:2021-06-22
  • Contact: Hua Chen
  • Supported by:
    National Natural Science Foundation of China(21772031); Natural Science Foundation of Hebei Province(B2019201398)

The benzimidazole-fused tricyclic iminosugars 1 and 2 derived from D-ribose inhibited β-glucosidase significantly. On the basis of the structural modification on the phenyl ring of 1 and 2, thirty novel tricyclic iminosugars 11a~11g, 12a~12g, 13a~13h and 14a~14h bearing mono-substituent on the different positions on phenyl ring were synthesized through Mitsunobu reaction. The inhibitory activities of newly synthesized compounds were tested against β-glucosidase (almonds). The results showed that compound 13e and the mixture of 13f and 14f exhibited significantly β-glucosidase inhibitory activities with IC50 values of 0.49 and 0.25 μmol/L, respectively, higher than that of the positive control, miglitol. The analysis of structure activity relationship (SAR) suggested that six-membered iminosugar ring in such fused tricyclic iminosugars was on the benefit of the compounds against β-glucosidase. The electron donor group on the 3' or 4' positions on the phenyl ring, such as methyl or methoxyl, would greatly promote the β-glucosidase inhibitory activities of the inhibitors.

Key words: fused tricyclic iminosugar, Mitsunobu reaction, β-glucosidase inhibitors, benzimidazole