Practical Synthesis of Bredemolic Acid, a Natural Inhibitor of Glycogen Phosphorylase

Bredemolic acid (3) is a naturally occurring 2 beta,3 alpha-isomer of maslinic acid (1) that is an allosteric site inhibitor of glycogen phosphorylase (GP). A practical synthesis of 3 was accomplished (18% yield) in five steps starting from the readily available 2 beta,3 beta-diol 6a. In a similar fashion, 2 beta,3 alpha-dihydroxyurs-12-en-28-oic acid (4) was synthesized as a natural 2 beta,3 alpha-isomer of corosolic acid (2). Compounds 3 and 4 exhibited significant inhibitory activity against rabbit muscle GPa with IC50 values of 6.25 and 1.1 mu M, respectively.