Lipase-catalyzed acetylation and esterification of bile acids

Abstract

In this chapter we describe the application of lipases as catalysts in reactions on a relevant family of steroids: the bile acids. Twenty three monoacetyl, diacetyl, and ester derivatives of deoxycholic, chenodeoxycholic, lithocholic, and cholic acids, 15 of them new compounds, were obtained through lipase-catalyzed acetylation, esterification, and alcoholysis reactions in very good to excellent yield and a highly regioselective way. Among them, acetylated ester products, in which the lipase catalyzed both reactions in one pot, were obtained. The influence of various reaction parameters in the enzymatic reactions, such as enzyme source, nucleophile/substrate ratio, enzyme/substrate ratio, solvent, and temperature, was studied. Some of the reported products are novel, and it is not possible to obtain them satisfactorily by following traditional synthetic procedures. Due to its singular structure containing three hydroxyl groups, cholic acid showed a different behavior in the enzymatic reactions, from that observed for the other three bile acids studied. In order to shed light to different behaviors of bile acids in the enzymatic reactions, molecular modeling was applied to substrates and some derivatives.