Synthesis and Biological Evaluation of Arjunolic Acid, Bayogenin, Hederagonic Acid and 4-Epi-hederagonic Acid as Glycogen Phosphorylase Inhibitors

AimTo study glycogen phosphorylase inhibitory activity of natural pentacyclic triterpenes bearing 23-hydroxy or 24-hydroxy.MethodsArjunolic acid, bayogenin, hederagonic acid and 4-epi-hederagonic acid were synthesized from oleanolic acid as the starting material and biologically evaluated as glycogen phosphorylase inhibitors.ResultsArjunolic acid, bayogenin, hederagonic acid and 4-epi-hederagonic acid were successfully semi-synthesized by multiple steps. The synthesis of arjunolic acid was via 11 steps in about 10% overall yield, and bayogenin via 14 steps in about 12% overall yield. Biological evaluation indicated that arjunolic acid, bayogenin, hederagonic acid and 4-epi-hederagonic acid showed moderate potency of glycogen phosphorylase inhibition with IC50 of 53-103 μmol·L−1.ConclusionArjunolic acid, bayogenin, hederagonic acid and 4-epi-hederagonic acid are glycogen phosphorylase inhibitors with moderate potency. Insert of 23-hydroxy or 24-hydroxy to oleanane skeleton has a tendency to be unfavorable to GP inhibition.