Study On Enzymatic Synthesis Of Paroxetine Chiral Intermediate In Organic Solvents

In this paper, lipase-catalyzed resolution of racemic paroxetine intermediate by asymmetric transesterification in organic solvents was studied. HPLC analysis of paroxetine intermediate was established, which work curve was Y=52894.7X-26242.1and with R2=0.99987. Chiral analysis method of paroxetine intermediate was established by chiral HPLC.To establish a fluorescent-based high throughput model for screening lipase production microorganisms which taking paroxetine intermediate as substrate and taking vinyl acetate as acyl donor, respectively. In the experiment, fluorescent excitation wavelengths is485nm and fluorescent emission wavelengths is538nm. the work curve of screening model is Y=10685X+176.15, with the correlation coefficient of0.9972. The screening result being combined with chiral HPLC analysis, we made the conclusion that Novozym435represents high eserification activity and stereoselectivity.The optimization of Novozym35catalyzed resolution of paroxetine intermediate was also studied. The optiomal enzymatic catalyzed condition was obtained and listed as following, which acyl donor, organic solvent, reaction temperature, reaction time, substrate concentration, rotation rate and molar ratio of substrate to acyl donor were vinyl acetate, dichloromethane,30℃,12h,200mM,200r/min and1:1, respectively. On this condition, the conversion rate was54%with e.e.s96.3%and E value40. When Novozym435was reused8times, enzymatic activity and stereoselectivity was almost kept the same. The study of Novozym435catalyzed resolution reaction laid a good basis for enzymatic synthesis of paroxetine chiral intermediate in industry scale application.