Synthesis and α-Glucosidase Inhibitory Activity of Oleanolic Acid Derivatives

doi:10.3969/j.issn.0251-0790.2012.04.018

Abstract

Abstract: 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.

Key words: Oleanolic acid, Structure modification, Mannich reaction, α-Glucosidase

CLC Number:

O629.6+1

TrendMD:

SONG Zhi-Cheng, WANG Shi-Sheng, SONG Qi-Ling, SHU Tao, ZHAO Wei-Jie. Synthesis and α-Glucosidase Inhibitory Activity of Oleanolic Acid Derivatives[J]. Chem. J. Chinese Universities, 2012, 33(04): 744.

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