Different behavior of bile acids in the enzymatic synthesis of esters and acyl derivatives

ALICIA BALDESSARI; M. ANTONELA ZÍGOLO; GUADALUPE GARCÍA LIÑARES

Trivandrum

Congreso; New Horizons in Biotechnology 2015; 2015

The Biotech Research Society

Bile acids are widely distributed in nature as oxygenated metabolites of steroids. The most common bile acids are: chenodeoxycholic (CDCA), deoxycholic (DCA) lithocholic (LCA) and cholic(CA) acids.Enzyme catalysis was applied to synthesize derivatives of these four bile acids.Twenty threemono-, diacetyl and ester derivatives of cholic, deoxycholic, chenodeoxycholicand lithocholic acid, fifteen 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 also obtained. Every product was completely identified and the influence of various reaction parameters in the enzymatic reactions was studied. A remarkable difference in the behavior of bile acids towards the enzymatic reactions was observed. For instance it was not possible to obtain acetylation products from CA by any of the tested lipases while CDCA and DCA afforded the 3-monoacetyl derivative using activated acetates as acetylating agents and the ethyl ester 3-AcO of LA was obtained in the presence of ethyl acetate. Regarding the esters, Candida antarcticalipaseB was the enzyme of choice for CDCA, DCA and LA while Rhizomucormiehei lipase was the best biocatalyst in the case of CA. In order to shed light to bile acids behavior in the enzymatic reactions, molecular modeling was applied to some derivatives. The determination of the binding energy and the distance between serine in the lipase catalytic site and reactive groups of the bile acids was useful to explain the variation in bile acids reactivity.