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 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.

[Retracted] A Network Pharmacology to Explore the Mechanism of Calculus Bovis in the Treatment of Ischemic Stroke

“…Methyl cholate is the methyl ester form of cholic acid, inhibiting the synthesis of cholesterol [35]. It has been reported that methyl cholate suppresses the growth of certain Grampositive and Gram-negative bacteria [36] and has a good anti-inflammatory effect [37]. Biliverdin is a type of bile pigment, an oxidized product of heme.…”

The use of polymer-supported Candida antarctica lipase B to achieve the entropically-driven ring-opening polymerization of macrocyclic bile acid derivatives via transesterification: selectivity of the reactions and the structures of the polymers produced

“…22 Interestingly, CO 2 CH 3 groups at the 24-position, which are present in many of the substrates studied, are not reported to react. 21,22 They do, however, react under more vigorous conditions since when cholic acid ( 21) is treated with a relatively large amount of CALB in tetrahydrofuran at 50 C for 7 days oligomerization occurs, i.e. the 3a-hydroxyl groups and 24CO 2 H groups of different molecules react together.…”

“…In previously published work with bile acid derivatives it has been shown that 3a-hydroxyl groups are acetylated efficiently when treated with CALB and vinyl acetate in tetrahydrofuran. 21,22 No reaction occurs with 7a-, 7b-and 12a-hydroxyl groups: see formula 1 for the numbering of bile acid derivatives. [21][22][23] The 3a-hydroxyl group of methyl cholate (20) is also selectively acylated when treated with various methyl or vinyl alkanoates and CALB.…”

“…21,22 No reaction occurs with 7a-, 7b-and 12a-hydroxyl groups: see formula 1 for the numbering of bile acid derivatives. [21][22][23] The 3a-hydroxyl group of methyl cholate (20) is also selectively acylated when treated with various methyl or vinyl alkanoates and CALB. 22 Interestingly, CO 2 CH 3 groups at the 24-position, which are present in many of the substrates studied, are not reported to react.…”

“…[21][22][23] The 3a-hydroxyl group of methyl cholate (20) is also selectively acylated when treated with various methyl or vinyl alkanoates and CALB. 22 Interestingly, CO 2 CH 3 groups at the 24-position, which are present in many of the substrates studied, are not reported to react. 21,22 They do, however, react under more vigorous conditions since when cholic acid ( 21) is treated with a relatively large amount of CALB in tetrahydrofuran at 50 C for 7 days oligomerization occurs, i.e.…”