水溶性汉防己甲素衍生物的合成

Synthesis of hydrophilic tetrandrine derivatives

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.