Optimization of Reaction Conditions on Kinetic Resolution of (R,S)-Naproxen 2,2,2- Trifluoroethyl Thioester by Using Lipase

摘要

In this study, the effect of organic solvents such as isooctane, octane, hexane, dodecane and heptane on kinetic resolution of racemic naproxen 2,2,2-trifluoroethyl thioester by using lipase was investigated. The isooctane showed the highest (S)-naproxen concentration (0.21 mM) in hydrolytic reaction. Conversion (47%) and reaction rate (199.0 mM -1 ·h) were the highest in dodecane. However, enantiomeric excess for (S)-naproxen (eep) in dodecane (86.9%) was lower than that of isooctane (99.8%). Therefore, among organic solvents used, isooctane was the most efficient for lipase-catalyzed resolution of (R,S)-naproxen 2,2,2-trifluoroethyl thioester. Also, the reaction conditions such as temperature, concentration of substrate and enzyme, and agitation speed were optimized by using response surface methodology (RSM). Based on statistical analysis, optimal conditions were determined to be 42.5 , 3.28 mM, 32.95 mg/mL and 164 ?? Rpm, respectively. Under optimal reaction conditions, the concentration of (S)-naproxen produced by the hydrolytic reaction of (R,S)-naproxen 2,2,2-trifluoroethyl thioester was 0.260 mM, similar to that of (S)-naproxen (0.266 mM) predicted by the model.