Enantioselective esterification of racemic ibuprofen with ethanol as reactant and solvent catalyzed by immobilized lipase: experimental and molecular modeling aspects

Abstract

In the last years enantioselective esterification of racemic ibuprofen performed in organic solvent media and catalyzed by lipases has been proposed as an effective way to increase the concentration of unesterified S-ibuprofen in the racemic mixture. In this contribution, a system free of organic solvent is proposed as a novel eco-friendly medium to perform the enantioselective enzymatic esterification of (R,S)-ibuprofen. Results showed that the reaction in excess of the esterifying alcohol in a system free of organic solvent is possible if the proper conditions are set. The effects of the amount of water present in the reaction medium, the volume of the alcohol used as acyl acceptor, the enzyme loading, and the reaction temperature, were alternatively analyzed in terms of the (conversion of ibuprofen towards the ester) reaction yield and enantiomeric excess achieved. Alcohol concentration showed to be determinant for both biocatalyst activity and enantioselectivity. The initial water content of reaction medium also showed to be a key parameter in a compromise between biocatalyst hydration and ester hydrolysis. By using 1 ml of ethanol as esterifying reagent, with an initial optimal water content of 4.8% v/v, at 45 °C, and with 160 mg of Novozym a total conversion of 62% and an enantiomeric excess of substrate of 54% were obtained in 72 hours of reaction.