含L-酪氨酸结构的五环三萜衍生物的合成及糖原磷酸化酶抑制活性研究

Synthesis of Pentacyclic Triterpenes Bearing L-tyrosine and Their Inhibitory Activity against Glycogen Phosphorylase

目的提高五环三萜化合物的活性,改善其水溶性。方法以五环三萜化合物积雪草酸、甘草次酸为原料,分别经过烷基化、水解等反应,在其羧基位引入L-酪氨酸结构片段。结果合成了4个含L-酪氨酸结构的五环三萜衍生物,并对所有目标化合物进行了糖原磷酸化酶抑制活性测试。结论甘草次酸的衍生物表现出了一定的糖原磷酸化酶抑制活性,其中化合物7(IC50=8.38μmol/L)抑制活性优异,超过其先导化合物甘草次酸(IC50=66μmol/L)。

Objective To enhance the activity and improve the water solubility of pentacyclic triterpenes. Methods The novel derivatives were synthesized by alkylation and hydrolysis reactions from asiatic acid and glycyrrhetic acid at whose carboxyl group the L-tyrosine fragment was introduced. Results Four novel derivatives bearing L-tyrosine fragment were synthesized and their inhibitory activities against glycogen phosphorylase （GP） were detected. Conclusion The derivatives of glycyrrhetic acid exhibited particular inhibitory activities against glycogen phosphorylase. Among them, compound 7 showed excellent inhibitive activity with IC50 of 8.38 μmol/L, which exceeded the IC50 of glycyrrhetic acid of 66 μmol/L.