熊果酸环磷酸酯衍生物的设计与合成

Design and Synthesis of 1,3-Cyclic Propanyl Phosphate Ester of Ursolic Acid

为降低熊果酸的体内代谢速度和延长体内保留时间,设计并合成了一类熊果酸环磷酸酯衍生物。以不同取代基取代的苯乙酮为起始原料,经酮酯缩合、还原、硅醚化、缩酮化及手性拆分、酸水解、磷酯化、酯交换等7步反应,得到了6个立体专一的熊果酸环磷酸酯衍生物。所合成化合物结构均经核磁共振波谱、高分辨质谱和旋光分析验证。

In order to avoid the quick metabolism of ursolic acid （UA）, a new class of potential prodrugs, 1, 3-cyclic propanyl phosphate esters of UA, was designed and synthesized. Six stereospecific derivatives of UA were synthesized using substituted acetophenone as starting material via condensation, reduction, trimethyl silylation, ketalization, chiral separation, hydrolysis, esterification and transesterification. All synthesized compounds were confirmed by NMR, HRMS and polarimetry techniques.