Enantioselective hydrolysis of racemic naproxen methyl ester by two-step acetone-treated Candida rugosa lipase

An optically pure (S)-naproxen was produced by two-step acetone-treated Can dida rugosa lipase (CRL) through enantioselective hydrolysis of racemic nap roxen methyl ester, The two-step acetone-treated CRL was much more enantios elective than the crude CRL towards the hydrolysis of (R,S)-naproxen methyl ester, yielding an enantiomeric excess (ee(p)) of >98% and an enantiomeric ratio (E) of >100. In terms of hydrolysis reaction rate and enantio select ivity, the optimal reaction conditions were found to be 37 degreesC and pH 6.0. The scaled-up production of (S)-naproxen was performed in a batch reac tor containing 200 ml of substrate solution (50 mM MES buffer containing 20 0 mM (R,S)-naproxen methyl ester). After 156 h of reaction, 38.4% of the in itial (R,S)-naproxen methyl ester was hydrolyzed, yielding an enantiomeric excess of 98% and an enantiomeric ratio of >100. Finally, (S)-naproxen was recovered from the reaction mixture with an optical purity of 98% and a rec overy yield of 95%. (C) 2001 Elsevier Science Ltd. All rights reserved.