Chinese Journal of Organic Chemistry ›› 2021, Vol. 41 ›› Issue (7): 2861-2874.DOI: 10.6023/cjoc202101055 Previous Articles     Next Articles



刘旭, 苏路路, 周昭希, 牛丽萍, 高利刚, 琚欢欢, 李丰兴, 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:2021-01-30 修回日期:2021-02-18 发布日期:2021-03-25
  • 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)

Design and Synthesis of Benzimidazole-Iminosugars and Their Inhibitory Activities against Glycosidases

Xu Liu, Lulu Su, Zhaoxi Zhou, Liping Niu, Ligang Gao, Huanhuan Ju, Fengxing Li, 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:2021-01-30 Revised:2021-02-18 Published:2021-03-25
  • Contact: Hua Chen
  • Supported by:
    National Natural Science Foundation of China(21772031); Natural Science Foundation of Hebei Province(B2019201398)

Based on our previous studies that benzimidazole-fused tricyclic iminosugars 1 and 2derived fromD-ribose inhibitedβ-glucosidase significantly, a series of novel tricyclic iminosugars 6a~6c and 7a~7c derived fromL -ribose and 2-deoxy-D-ribose, respectively, were designed and synthesized through the key Mitsunobu reaction. Additionally, based on the drug design method of isosterism, a series of tricyclic iminosugars derivitives 13a,13b and 17a~17e containing amino group on C-2 position, and 28a and 28b with alkoxyl group on C-4 position on sugar ring were designed. Compounds 13a and 13b were synthesized through substitution reaction of benzylamine and methylsulfonide hydroxy (OMs), while compounds 17a~17e were prepared through ring opened reaction of amine and the three-membered epoxy intermediate 15, compounds 28a and 28b were synthesized through nucleophilic substitution reaction of 4-OH and halohydrocarbon. The inhibitory activities of compounds 6a~6c,7a~7c,13a,13b,15,17a~17e,19,28a and 28bagainstα-glucosidase (Aspergillus niger),β-glucosidase (almonds) andα-galatosidase (coffee beans) were tested. The results showed that the tested compounds exhibited no or weakα-glucosidase andα-galatosidase inhibitory activities at 10 μmol/L. Some compounds exhibited good inhibitory activities againstβ-glucosidase. Among them, the epoxy intermediate 15 and compound 17a(2-amino) were the best ones with IC50values of 10.5 and 11.7 μmol/L, respectively, but lower than that of the positive control 1. The results further suggested that such fused tricyclic iminosugars were the excellent and specific inhibitors againstβ-glucosidase.

Key words: fused tricyclic iminosugar, Mitsunobu reaction, glycosidase inhibitors, benzimidazole, epoxy intermediate