Abstract: In this study,oleanolic acid derivatives were designed and synthesized from oleanolic acid,which is a natural pancreatic lipase inhibitor. The structures of synthesized derivatives was characterized by ¹H NMR, ¹³C NMR and MS. Their inhibitory effects on pancreatic lipase were tested and their interaction mechanisms were analyzed. Results showed that two new oleanolic acid derivatives:oleanane-28-β-lactone (IC₅₀:16.4 μmol/L) and oleanane-28-α,β-unsaturated ester (18.5 μmol/L), had higher inhibitory effects than oleanolic acid (IC₅₀:87.7 μmol/L),and reached to 5.35 and 4.74 times to that of oleanolic acid,respectively. Oleanolic acid and oleanane-28-α,β-unsaturated ester belonged to mixed type inhibition. However,oleanane-28-β-lactone changed to competitive inhibition. Their inhibitory activities on pancreatic lipase were related to hydrogen bonds and hydrophobicity.

Key words: pancreatic lipase, oleanolic acid derivatives, inhibition of enzyme activity, inhibition type