齐墩果酸的结构修饰和α-葡萄糖苷酶抑制活性

以天然五环三萜类化合物齐墩果酸为原料, 通过氧化、酯化、环合和曼尼希等反应, 对A环2, 3位和28位进行结构修饰, 设计合成了16个衍生物; 通过理化性质、质谱和核磁数据确定了化合物结构. 对合成的衍生物进行了体外α-葡萄糖苷酶抑制活性筛选, 结果表明, 受试化合物在200 μg/mL浓度下显示出不同程度的酶抑制活性. 初步构效关系分析表明, 28位游离羧基是活性必需基团, 3位羟基或相应的氢键供体取代基有利于提高活性.

Synthesis and α-Glucosidase Inhibitory Activity of Oleanolic Acid Derivatives

The natural pentacyclic triterpene compound,oleanolic acid,has a series of biological activities,such as antitumor,anti-HIV,hypoglycemic and liver protective activities,but its relatively weak activities and low bioavailability limit its clinical applications.In order to investigate the hypoglycemic activity of oleanolic acid derivatives,sixteen derivatives were synthesized by modification of oleanolic acid at C2,C3 and C28 positions via oxidation,esterification,cyclization,Mannich reaction and so on.Their structures were determined by physicochemical properties,MS and NMR data.Their in vitro inhibitory activities against α-glucosidase were tested.The results show that all the tested compounds exhibit α-glucosidase inhibitory activities in various degrees at the concentration of 200 μg/mL.Among them,3-oxo and 28-ester derivatives(2,5—7) show lower inhibitory activity than oleanolic acid.The preliminary analysis of structure-activity relationship revealed that the free carboxyl group at C28 was indispensable and hydroxyl or other hydrogen-bond donor groups at C3 contributed to increase inhibitory activity.