水溶性汉防己甲素衍生物的合成  

Synthesis of hydrophilic tetrandrine derivatives

作　　者：谢广通 蒋太白 焦子伟 朱月 李金玉 潘卫东 XIE Guang-tong;JIANG Tai-bai;JIAO Zi-wei;ZHU Yue;LI Jin-yu;PAN Wei-dong(College of Pharmacy,Guizhou University of Traditional Chinese Medicine,Guiyang 550025;Natural Products Research Center of Guizhou Province,Guiyang 550014;Guiyang Healthcare Vocational University,Guiyang 550081;Zunyi Medical University,Zunyi Guizhou 563006;College of Pharmacy,Guizhou University,Guiyang 550025)

机构地区：[1]贵州中医药大学药学院,贵阳550025 [2]贵州省天然产物研究中心,贵阳550014 [3]贵阳康养职业大学,贵阳550081 [4]遵义医科大学,贵州遵义563006 [5]贵州大学药学院,贵阳550025

出　　处：《中南药学》2024年第4期884-891,共8页Central South Pharmacy

基　　金：国家自然科学基金项目(No.81960635);贵州省科学技术基金项目(黔科合基础-ZK[2021]一般558)。

摘　　要：目的 研究改善汉防己甲素水溶性和生物利用度。方法 设计汉防己甲素衍生物合成路线:以汉防己甲素为起始原料,经过硝化反应、还原反应、酰胺缩合反应、点击化学和消去反应得到目标衍生物。所有衍生物均通过ESI-MS、^(1)H NMR、^(13)C NMR进行结构表征,并对选定的化合物进行水溶性评价。结果 首次合成10个汉防己甲素糖苷衍生物和1个汉防己甲素C-14酰胺衍生物。结论 汉防己甲素糖苷衍生物水溶性显著提升,其中1b汉防己甲素麦芽糖衍生物水溶性最好,具有进一步研究价值。Objective To improve the poor water solubility and low bioavailability of tetrandrine and its clinical applications.Methods The synthetic routes of tetrandrine derivatives were designed.The target derivatives were obtained by nitration reactions,reduction reactions,amide condensation reactions,click chemistry,and elimination reactions with tetrandrin as the starting point.All the derivatives were elucidated by ESI-MS,^(1)H NMR,and ^(13)C NMR spectra.The aqueous solubility of selected compounds were evaluated.Results Totally 10 glycoside tetrandrine derivatives and one C-14 amide tetrandrin derivatives were first synthesized.Conclusion The water solubility of the glycoside tetrandrine derivatives is greatly improved,and compound 1b,the tetrandrin maltose derivative,exhibits notable water solubility for further research.

关 键 词：汉防己甲素 糖苷衍生物 点击化学 水溶性 

分 类 号：R284.1[医药卫生—中药学]