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

MARÍA L. FORESTI; MARIANELA GALLE; MARÍA L. FERREIRA; LAURA E. BRIAND

JOURNAL OF CHEMICAL TECHNOLOGY AND BIOTECHNOLOGY

JOHN WILEY & SONS LTD

Año: 2009 vol. 84 p. 1461 - 1473

0268-2575

BACKGROUND: In recent years enantioselective esterification of racemic ibuprofen performed in organic co-solvent media such as isooctane and cyclohexane and catalyzed by lipases, has been proposed as an effective way to increase the concentration of S-ibuprofen in the racemic mixture. In this contribution, the enantioselective enzymatic esterification of (R,S)-ibuprofen with ethanol catalyzed by commercial Novozym 435 without the addition of a co-solvent is thoroughly investigated. Experimental data are further analyzed considering the results of extensive molecularmodeling calculations. RESULTS: The conversion of ibuprofen towards the ethyl esters and the enantiomeric excess towards S-ibuprofen are greatly affected by the ethanol and water contents of the reaction media. The optimum conditions for the esterification of racemic ibuprofen in a batch-type reactorwere as follows:molar ratio of ethanol to ibuprofen=7, 4.8% v/v ofwater, 160 mgof Novozym 435, 45 ◦C and 200 rpm. Under these conditions an enantiomeric excess of 54% and 63% of ibuprofen conversionwere reached. CONCLUSIONS: Results showed that the reaction in excess of the esterifying alcohol in a system free of additional organic solvents is possible if the proper conditions are set. Molecular modeling calculations demonstrated that the formation of dead-end compounds between the enzyme and ethanol/watermay account for lipase inhibition at high concentrations of those compounds.