Synthesis of 3-Deoxypentacyclic Triterpene Derivatives as Inhibitors of Glycogen Phosphorylase

The 3-deoxy-2-keto derivatives 5 and 7 of oleanolic acid (1) and ursolic acid (2), respectively, served as precursors to the synthesis of 35 3-deoxy derivatives of pentacyclic triterpenes. The synthesized compounds were biologically assayed for their inhibitory activity against rabbit muscle glycogen phosphorylase a (GPa). Among this series of compounds, 2(2 alpha-hydroxyurs-12-en-28-oic acid (18) (IC50 = 1.2 mu M) exhibited the most potent activity. Preliminary structure-activity relationship analysis for the 3-deoxy triterpene derivatives as GP inhibitors is also discussed.