Glycosylation Of Dihydroxylpentacyclic Triterpene Carboxylic Acids As Inhibitors Of ?-glucosidase

Based on the dihydroxylpentacyclic triterpene carboxylic acids(maslinic acid and corosolic acid) with hypoglycemic activity isolated from Cyclocarya paliurus(Batal.) Iljinskaja, the paper design synthetic routes to prepare maslinic acid(MA) and corosolic acid(CA) with oleanic acid(OA) and ursolic acid(UA) and to synthesize trichloroacetimidate of monosaccharides and disaccharides with xylose, glucose, arabinose, ribose, lactose, maltose. Then, a series of compounds were synthesized by glycosylation of MA and CA, and the structures of the derivatives were elucidated by standard spectroscopic methods including 1H NMR, 13 C NMR and HRMS. The ?-glucosidase inhibitory activities of all the novel compounds were evaluated in vitro. The solubility and inhibitory activity of ?-glucosidase assays showed that the bis-disaccharide glycosides of triterpene acids possessed higher water solubility and ?-glucosidase inhibitory activities than the bis-monosaccharide glycosides. Among these compounds, maslinic acid bis-lactoside(3-29, IC50 = 684 ?M) and corosolic acid bis-lactoside(3-35, IC50 = 428 ?M) had the best water solubility, and 3-35 exhibited a better inhibitory activity than acarbose(IC50 = 478 ?M). However, most of glycosylated derivatives possessed lower inhibitory activities than the parent compounds, although their water solubility was enhanced obviously. Moreover, the kinetic inhibition studies indicated that 3-35 was a non-competitive inhibitor, and structure–activity relationships of the derivatives are also discussed.