高等学校化学学报

高等学校化学学报

• 研究论文 • 上一篇    下一篇

高化学和立体选择性合成泽兰素衍生S-糖苷及α-葡萄糖苷酶抑制活性评价

赵宇,付子帅,张颖,李林轩,刘朝霞,姚辉,黄年玉,王能中   

  1. 三峡大学生物与制药学院, 天然产物研究与利用湖北省重点实验室
  • 收稿日期:2025-12-22 修回日期:2026-01-15 网络首发:2026-01-17 发布日期:2026-01-17
  • 通讯作者: 李林轩 E-mail:lilinxuan@ctgu.edu.cn
  • 基金资助:
    国家自然科学基金(批准号: 22207063, 22501156)、湖北省中央引导地方科技发展资金(批准号: 2024BSB016, 2025CSA093)、湖北省自然科学基金(批准号: 2025AFD262, 2025AFB213)、高等学校学科创新引智计划(批准号: D20015)和天然产物研究与利用湖北省重点实验室(三峡大学)开放基金(批准号: 2024NPRD03~2024NPRD05, 2025NPRD01)资助

Highly Chemo- and Stereoselective Synthesis of S-Glycosides from Euparin: Evaluation of Their α-Glucosidase Inhibitory Activity

YU Zhao, FU Zishuai, Zhang Ying, LI Linxuan*, LIU Zhaoxia*, YAO Hui, HUANG Nianyu, WANG Nengzhong*   

  1. College of Biological and Pharmaceutical Sciences, Hubei Key Laboratory of Natural Products Research and Development, China Three Gorges University
  • Received:2025-12-22 Revised:2026-01-15 Online First:2026-01-17 Published:2026-01-17
  • Contact: Lin-Xuan LI E-mail:lilinxuan@ctgu.edu.cn
  • Supported by:
    Supported by the National Natural Science Foundation of China(Nos. 22207063, 22501156), the Hubei Provincial Central Government Guided Local Science and Technology Development Project(Nos. 2024BSB016, 2025CSA093), the Hubei Provincial Natural Science Foundation of China(Nos. 2025AFD262, 2025AFB213), the 111 Project(D20015), and the Opening Funding of Hubei Key Laboratory of Natural Products Research and Development(China Three Gorges University, Nos. 2024NPRD03~2024NPRD05, 2025NPRD01)

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摘要： 以泽兰素为苷元设计合成新型S-糖苷衍生物, 采用钯催化策略, 在温和反应条件下实现了22个S-糖苷化合物的高化学选择性、高立体选择性合成. 体外α-葡萄糖苷酶抑制活性评价结果显示, 化合物5a、5d和7表现出强效抑制活性, IC??值分别为2.7 μmol/L、5.7 μmol/L和12.1 μmol/L. 分子对接研究表明, 这些活性化合物通过与α-葡萄糖苷酶活性位点的ASP382、HIS326残基形成氢键, 及与PHE144残基发生π-π堆积作用, 稳定结合于靶酶活性口袋, 结合能达-32.409 kJ/mol. 本研究建立了温和高效的泽兰素S-糖苷合成方法, 为新型抗糖尿病药物研发提供了具有潜力的先导化合物, 也为天然产物的结构修饰提供了新思路.

关键词: 糖尿病, 泽兰素, α-葡萄糖苷酶, S-糖苷, 钯催化

Abstract: Herein, a novel S-glycoside derivatives were designed and synthesized using euparin as the aglycone. Employing a palladium-catalyzed strategy, 22 S-glycosides were efficiently synthesized under mild conditions with high chemoselectivity and stereoselectivity. Evaluation of the in vitro α-glucosidase inhibitory activities of these compounds showed that compounds 5a, 5d, and 7 exhibited potent inhibitory activity, with IC?? values of 2.7 μmol/L, 5.7 μmol/L, and 12.1 μmol/L, respectively. Molecular docking studies revealed that these active compounds bind to the active site of α-glucosidase through hydrogen bonds(with ASP382 and HIS326 residues) and π-π stacking interactions(with PHE144 residue), contributing to high binding affinity(docking score: -32.409 kJ/mol). This study provides a mild and efficient synthetic method for euparin-derived S-glycosides and identifies promising lead compounds for the development of novel anti-diabetic drugs.

Key words: Diabetes mellitus, Euparin, α-Glucosidase, S-Glycoside; Palladium catalysis

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