Enzymatic Resolution Of Racemic Ibuprofen

In order to resolute racemic ibuprofen enantioselectively in organic solvent, a series of researches were canied out:Firstly, the conditions of the HPLC analysis were optimized, and a strain of Penicillium expansum TS414 was screened, which could secrete a lipase with perfect enantioselectivity.Secendly, the main variables affecting the resolution reaction by the lipase were optimized, including water concentration, temperature, the organic solvent, enzyme concentration, the structure and the concentration of alcohol. Under optimum conditions (6.46 mmol/L ibuprofen, 53.3 g/L lipase, 40 mmol/L 1-propanol, 15 mL isooctane, 0.5%(v/v) water, 60℃for 50 h), the total conversion rate and the enantiomeric ratio could reach 42% and 429.63, respectively.Thirdly, the immobilization conditions of Penicillium expansum TS414 lipase were optimized, and macroporous adsorptive resion AB-8 was proved to be a suitable carrier for immobilization of Penicillium expansum TS414 lipase. The optimized conditions were as follows: lipase: resion= 6:1, pH 9.0, adsorbing 6 h, lyophilizing 2 h. By further studying, it may be proved that the effect of the resolution of the (R,S)-ibuprofen was perfect when the reaction temperature and rotation speed was 40℃and 200 rpm, respectively. Then the optimum concentrations of the ibuprofen, n-propanol and immobilized lipase were determined by the uniform design. Under the optimum condition of 15 mL isooctane, 20.84 mg ibuprofen, 42.26μL n-propanol and 0.6 g immobilized lipase, the determine value of the ee_s is 81.12%.In the end, a kinetic study of esterification reaction for resolution of (R,S)-ibuprofen by the immobilized Penicillium expansum TS414 lipase was researched. Then, the experimental data was analysis by the origin 7.5, and the parameters in the kinectic equation were determined by non-linear regression: V_max=1.11173 mmol/h.L, K_A=4.64111 mmol/L, K_B=0.25143 mmol/L, K_iB=182.31537 mmol/L.