Synthesis And Activity Of Oleanolic Acid Derivatives

Saponins are largely distributed in nature with significant pharmacological activities. They are the major biologically active ingredients in many Chinese traditional herbs. Oleanolic acids are triterpenoid compounds, which are widespread ubiquitous natural, and have been associated with a wide variety biological activities. Twenty-four sugar-substituted oleanolic acid derivatives (1a-1f,2a-2j, and3a-3h) were synthesized in a concise and efficient strategy and their effects on the inhibition of protein tyrosine phosphatase1B (PTPIB) and insulin-sensitizing response were evaluated in vitro. Several derivatives showed moderate to good inhibitory activities against PTPIB, and especially compounds2f,2h,3d and3e exhibited the most potent inhibitory activities with the IC50values of1.91,12.2,9.21and0.56μM against PTP1B, respectively. Furthermore, compounds2g-2h and3b-3e displayed good insulin-sensitizing activities with the response values ranging from21.52%to59.58%. Structure-activity relationship study of these sugar-substituted oleanolic acid derivatives demonstrated that PTP1B inhibitory activity and insulin-sensitizing response were strongly influenced by both the carbohydrate moiety at the C-3position and the long acidic chain at C-28position of oleanolic acid.