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.
Cheng
Keguang
K
Center for Drug Discovery, College of Pharmacy, China Pharmaceutical University, 24 Tongjia Xiang, Nanjing 210009, People's Republic of China.
Zhang
Pu
P
Liu
Jun
J
Xie
Juan
J
Sun
Hongbin
H
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