Study On The Chemical Modification Of Lipase And Applied In Chiral Resolution Of Racemic Paroxol

Lipase is an important and widely used industrial enzyme. It is widely used inpharmaceutical, chemical, food, feed and energy industries because it has someimportant features, such as high selectivity, high stability, mild reaction conditions,without coenzyme. At the present’s time, paroxetine is one of eight kinds ofantidepressants on the market’s best-selling, Currently, Paroxol was obtained bychemical method. The main contents of this work were as follows:(1) Lipase from Candida rugosa at the highest conversion was screened for thechiral resolution of racemic paroxol. Effect of different operating conditions, such asmolar ratios of substrate, enzyme concentration, reaction temperature, mass transfer,and reaction time was studied. Under the optimum conditions of10g/l of enzymeconcentration,100r/min of stirring rate, substrate molar ratios of5:1at35°C for18h,a satisfactory conversion (46.95%) was obtained.(2)This lipase was modified with different anhydrides, such as phthalicanhydride (PA), succinic anhydride (MA). The optional temperature, thermal stability,the resistance to organic solvents the stability in organic solvents for the native andmodified lipase were compared. The thermal stability for the modified lipase wasobviously improved. The resistance to organic solvents and stability in organicsolvents were improved, too. The UV spectra showed that the modification lead to thechange of the structure of the enzyme. Compared with nature enzyme, the conversionrate for modified lipase of esterification tocopherol succinate was improved whencompared with native lipase.(3) Lipase-mediated chiral resolution of racemic paroxol was optimized by centralcomposite design under response surface methodology. Optimal conditions were:temperature35°C, substrate molar ratio7.81:1, stirring rate160r/min, and reactiontime0.5d. Obviously, central composite design under response surface methodologyto be useful for synthesis of vitamin C palmitate by lipase and statistical analysis wasproved to be a useful and powerful tool in developing optimal synthesis conditions.