Practical synthesis of bredemolic acid, a natural inhibitor of glycogen phosphorylase.
Bredemolic acid (3) is a naturally occurring 2β,3α-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 2β,3β-diol 6a. In a similar fashion, 2β,3α-dihydroxyurs-12-en-28-oic acid (4) was synthesized as a natural 2β,3α-isomer of corosolic acid (2). Compounds 3 and 4 exhibited significant inhibitory activity against rabbit muscle GPa with IC(50) values of 6.25 and 1.1 μM, respectively.
Center for Drug Discovery, College of Pharmacy, China Pharmaceutical University, 24 Tongjia Xiang, Nanjing 210009, People's Republic of China.
Keguang
K
Cheng
Pu
P
Zhang
Jun
J
Liu
Juan
J
Xie
Hongbin
H
Sun
D000818:Animals; D024981:Glycogen Phosphorylase / Q000037:antagonists & inhibitors*; D009132:Muscles / Q000201:enzymology; D009828:Oleanolic Acid / Q000138:chemical synthesis / Q000494:pharmacology / Q000031:analogs & derivatives; D011817:Rabbits; D013237:Stereoisomerism; D014315:Triterpenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
D014315:Triterpenes; D009828:Oleanolic Acid; C113861:corosolic acid; C412811:maslinic acid; D024981:Glycogen Phosphorylase