Enzymatic Kinetic Separation Of Enantiomers Of Aromatic Acids

In this paper,the study used commercial lipases as a catalyst.An efficient reactive system was constructed for enzymatic kinetic resolution of(+,-)-2,3-diphenylpropionic acid methyl ester((+,-)-2,3-2-PPAME),carprofen methyl ester((R,S)-CPME)and(+,-)-2-(4-methylphenyl)propionic acid methyl ester(2-(4-MP)PPAME)in an aqueous medium,and enhanced resolution performance by adding ?-cyclodextrin derivatives.The effects of temperature,pH,concentration of enzyme,concentration of ?-cyclodextrin,amount of substrate and reaction time on the conversion of substrate and the optical purity of product were investigated.The enzyme-catalyzed kinetic resolution system was optimized by RSM and other method.1.The enantioselective catalytic hydrolysis of(+,-)-2,3-2-PPAME by different lipases was studied.Candida antarctica lipase A(CALA)is the best catalyst.Hydroxypropyl-?-cyclodextrin(HP-?-CD)was added to the reaction system to increase the solubility of 2,3-2-PPAME,which resulted in an increase of 35.56%in substrate conversion remaining the high enantiomeric excess obtained.The influence of a series of important parameters on the conversion of substrate and the optical purity of product was also investigated.The reaction conditions were optimized and the optimal reaction conditions were obtained,including temperature 60 ?,pH 5.50,30 mg/mL CALA,25 mmol/L HP-?-CD,0.12 mmol substrate and 40 h for reaction time.Under these conditions,the substrate conversion was up to 44.07%and the optical purity of product was up to 98.20%.2.For the enantioselective catalytic hydrolysis of(R,S)-CPME reaction system,the CALA as the best catalyst.Hydroxyethyl-?-cyclodextrin(HE-p-CD)was added into the reaction system to increase the solubility of(R,S)-CPME in the reaction system,which significantly enhanced the substrate conversion from 11.12%to 30.84%,and also increased the optical purity of the product.The response surface methodology(RSM)was used to optimize the process parameters and to obtain the optimum process conditions,including reaction temperature 76 ?,pH 6.0,40 mg/mL CALA,0.05 mmol substrate,40 mmol/L HE-?-CD and 30 h for reaction time,under which,the reaction yielded(S)-CP with 96.24%enantiomeric excess and 46.07%overall conversion.3.An efficient reactive system was construct for enantioselective hydrolysis of(+,-)-2-(4-methylphenyl)propionic methyl ester(2-(4-MP)PPAME),selection of Candida rugosa lipase(CRL)as the best catalyst.HP-?-CD was added to the aqueous system,which resulted in an increase of 45.28%in substrate conversion remaining the high enantiomeric excess obtained.Response surface methodology and experiment design were employed to model and optimize the reaction system.The optimal conditions for this reaction was obtained,including temperature at 39 ?,pH of 6.60,12.5 mg/mL CRL,35 mmol/L HP-?-CD,0.06 mmol substrate and 40 h for reaction time.Under these optimal conditions,the substrate conversion was up to 41.32%and the optical purity of the product was up to 95.22%.