大学化学 >> 2024, Vol. 39 >> Issue (6): 342-349.doi: 10.3866/PKU.DXHX202311070

所属专题： 第4届全国大学生化学实验创新设计大赛

化学实验 上一篇    下一篇

绿色化学导向的一步法贝诺酯合成工艺研究及其体内动态评价

李炳良1, 韩玉莹1, 李典阳1, 刘丹丹1,2, 尚文斌1,2   

  1. 1 昆明医科大学药学院暨云南省天然药物药理重点实验室, 昆明 650500;
    2 昆明医科大学现代生物医药产业学院, 昆明 650500
  • 收稿日期:2023-11-21 修回日期:2024-01-05 发布日期:2024-06-07
  • 通讯作者: 刘丹丹, 尚文斌 E-mail:liudandan@kmmu.edu.cn;shangwenbin@kmmu.edu.cn
  • 基金资助:
    国家自然科学基金地区基金(22367018)；云南省科技厅-昆明医科大学应用基础研究联合专项面上基金资助项目(202201AY070001–005)；云南省科技厅基础研究专项青年项目(202201AU070135)

One-Step Synthesis of Benorilate Guided by Green Chemistry Principles and in vivo Dynamic Evaluation

Bingliang Li1, Yuying Han1, Dianyang Li1, Dandan Liu1,2, Wenbin Shang1,2   

  1. 1 School of Pharmaceutical Sciences and Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming 650500, China;
    2 College of Modern Biomedical Industry, Kunming Medical University, Kunming 650500, China
  • Received:2023-11-21 Revised:2024-01-05 Published:2024-06-07
  • Contact: Dandan Liu, Wenbin Shang E-mail:liudandan@kmmu.edu.cn;shangwenbin@kmmu.edu.cn

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摘要： 现行教材中贝诺酯的合成基于Schotten-Baumann酯化反应，实验试剂SOCl2会转化生成HCl和SO2，环境友好性低，且实验步骤多。本改进实验利用碳二酰亚胺/4-DMAP缩合酯化反应一步合成贝诺酯，通过熔点测定、NMR、HPLC-MS等对产品进行结构表征与纯度测定，并进行基于大鼠血浆和胆汁的体内动态分析。同时验证了药物设计拼合原理，改进后的方法绿色高效，安全性明显提高。

关键词: 贝诺酯, 一步合成, 碳二酰亚胺, 体内分析, 拼合原理

Abstract: The current synthesis of benorilate typically involves the Schotten-Baumann esterification, which generates harmful gases HCl and SO2 from the reagent SOCl2, posing environmental concerns. Moreover, the process entails multiple steps. In this study, we have optimized a one-step method using EDCI/4-DMAP esterification for the synthesis of benorilate. The product’s structure and purity were characterized through melting point determination, NMR, and HPLC-MS analysis, followed by in vivo dynamic evaluation in rats based on plasma and bile samples. This evaluation confirmed the principles of drug design. The improved method not only enhances efficiency but also significantly improves experimental safety.

Key words: Benorilate, One-step synthesis, EDCI, In vivo analysis, Combination principles