LIPASE-CATALYZED ENANTIOSELECTIVE ESTERIFICATION OF IBUPROFEN IN ORGANIC-SOLVENTS UNDER CONTROLLED WATER ACTIVITY

The enantioselective esterification or ibuprofen (2-(4-iso-butylphenyl )propionic acid), catalyzed by Candida. antarctica lipase (type B), wa s performed in various organic solvents. The reactions were conducted in controlled water activity atmospheres, thereby permitting the influ ence of the solvents to be separated from their ability to strip water from the solid enzymes. Even in these constant water activity conditi ons, hydrophobic solvents allow higher enzyme activity than hydrophili c ones, indicating that hydrophilic solvents impede enzyme activity in essence and not because they strip water from the enzyme. The highest enantioselectivity was obtained in solvents leading to low reaction r ates. Different properties were used to describe the solvents, namely the hydrophobicity, quantified by log P; epsilon, the dielectric const ant: and E-T(N), a normalized electron acceptance index. None gave a c lear and predictive portrait of the influence of the solvent, however, the hydrophobicity was the most satisfactory. This could be linked to the solubility of ibuprofen, which varies linearly with the value of log P. The highest enantioselectivity was observed at low water activi ties. This is caused by different effects of water activity on the rea ction rates with the two isomers. The activity toward the less favored one decreased after reaching a maximum while the rate with the other isomer continued to rise when a(W) decreased. (C) 1998 Elsevier Scienc e Inc.