HIGH ENANTIOSELECTIVE ESTERIFICATION OF 2-ARYLPROPIONIC ACIDS CATALYZED BY IMMOBILIZED LIPASE FROM CANDIDA-ANTARCTICA - A MECHANISTIC APPROACH

In order to study the mechanism of the enantioselective esterification of 2-arylpropionic acids catalyzed by lipases, a systematic study of the enzymatic activity of immobilized lipase from Candida antarctica (SP435A) in this reaction has been carried out. The main variables that have a positive effect on the reaction rate are temperature, amount of catalyst, reaction time, and an acid/alcohol molar ration of 1:1. The enzyme is enantioselective in the esterification of R(-) acid. Therefore the S(+) form, with pharmacological activity, can be prepared by enantioselective esterification of the racemate at temperatures below 24 degrees C and at conversions greater than 50%. The racemic temperature in the esterification of (+/-)-ibuprofen is 65.4 degrees C. In the esterification of (+/-)-2-phenylpropionic acid, isooctane is the best solvent. The reactivity observed is (+/-) ketoprofen > (+/-)-2-phenylpropionic acid > (+/-)-ibuprofen > (+/-)-naproxen = (+/-)-flurbiprofen in isobutyl methyl ketone saturated with water, a solvent in which all these antiinflammatory drugs are soluble and the enzymatic derivative is active. A qualitative model of the active site of this immobilized enzyme is described.