Efficient lipase-catalyzed preparation of long-chain fatty acid esters of bile acids: biological activity and synthetic application of the products.
A highly regioselective (3-position) and efficient (quantitative yield) acylation of bile acids catalyzed by immobilized Candida antarctica lipase was established. Methyl cholate derivatives acylated with long-chain fatty acids (C12-C16) showed an inhibitory effect on the growth of some strains of Gram-positive and -negative bacteria (27-400 micrograms/ml). The anti-bacterial activity was slightly weaker than has been observed for methyl cholate, while the increased lipophilicity and lower melting points of the present derivatives are well suited for a potential germicide which would be safe and be topically applied. This enzyme-catalyzed transesterification is also demonstrated as an expeditious route to ursodeoxycholic acid, in respect of the regioselective introduction of acyl protecting groups on the hydroxyl groups of the intermediates. 7-Ketolithocholic acid, a known direct precursor of ursodeoxycholic acid, was obtained from cholic acid via chenodeoxycholic acid in a 46% yield and 9 steps.
Sugai
T
T
Department of Chemistry, Keio University, Yokohama, Japan.
Takizawa
M
M
Bakke
M
M
Ohtsuka
Y
Y
Ohta
H
H
D000215:Acylation; D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects; D001647:Bile Acids and Salts / Q000138:chemical synthesis* / Q000494:pharmacology; D002175:Candida / Q000201:enzymology; D005227:Fatty Acids / Q000138:chemical synthesis* / Q000494:pharmacology; D008049:Lipase / Q000737:chemistry*; D008826:Microbial Sensitivity Tests
D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D001647:Bile Acids and Salts; D005227:Fatty Acids; D008049:Lipase