Synthesis and Evaluation of a Series of Oleanolic Acid Saponins as -Glucosidase and -Amylase Inhibitors

Sixteen naturally occurring oleanolic acid saponins and their derivatives were synthesized in an efficient and practical strategy, and their inhibitory activities against -glucosidase and -amylase were evaluated in vitro. Among all the compounds, 28-O-monoglucoside 8 exhibited remarkably potent inhibitory activity against -glucosidase with an IC50 value of 87.3 mu M, which was fivefold stronger than that of the antidiabetic acarbose. Based on the preliminary structure-activity relationships, for 28-O-monoglucosides, the presence of a terminal -l-rhamnopyranosyl residue enhanced the -glucosidase and -amylase inhibitory activities. Furthermore, for 3,28-O-bidesmosides, sugar-substituted moieties attached to the C-3 and C-28 positions of the oleanolic acid scaffold are helpful to increase the inhibitory activities against -amylase and -glucosidase.