Efficient Lipase-catalyzed Preparation of Long-chain Fatty Acid Esters of Bile Acids: Biological Activity and Synthetic Application of the products

Abstract

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 μg/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 460% yield and 9 steps.