Enzyme-catalyzed reactions in organic media of rac-ketoprofen esters w
ith different nucleophiles such as alcohols, amines, and water have be
en studied. Among the parameters optimized are the enzyme, the activat
ed substrate, and the solvent. With the enzymes used in this study the
preferred substrate was the trifluoroethyl ester of rac-ketoprofen (r
ac-2), whose (R)-enantiomer reacted preferentially. The enzyme of choi
ce was the lipase M-AP-10 from Mucor miehei and best results were obta
ined with diisopropyl ether as solvent. Three different methods have b
een scaled-up for the resolution of 75-150 g of substrate: transesteri
fication with 1-butanol (90% yield of (S)-ketoprofen, 88% ee), transes
terification with 2-(2-pyridyl)ethanol (94% yield, 92% ee), and hydrol
ysis in wet organic solvent (93% yield, 97% ee). Despite the comparabl
e chemical and optical yields obtained with these three methods, the u
se of 2-(2-pyridyl)ethanol and the hydrolysis allowed a much easier wo
rk-up and isolation of the desired (+)-(S)-ketoprofen. (C) 1993 Wiley-
Liss, Inc.