Enzymatic Kinetic Resolution Of Transesterification Of 1-(4-Chloro-2-methoxy-3-menthyl-phenyl)-propan-2-ol In Organic Media

The enzymatic resolution of 1-(4-Chloro-2-methoxy-3-menthyl-phenyl)-propan-2-ol, a useful intermediate in the synthesis of Fufenozid, was investigated.Through screening, the preferable system for the asymmetric reaction were:Novozym 435, hexane and vinyl acetate. Effects of various parameters were studied to get preferable results. The optimize condition was as following: when the concentration of 1-(4-Chloro-2-methoxy-3-menthyl-phenyl)-propan-2-ol and vinyl acetate were all 93.16 mmol/1, the concentration of enzyme was 2 mg/ml, 40 °C and 230 rpm were a good choice. In this condition, the conversion, ee_s and ee_p reached 50.34% , 97.33% and 95.99% after 14 hour. Enzyme activity began to be stable after some runs of utilization.The deaction of the lipase in hexane was investigated, the deaction equation is expressed as follow: C_Em = C_E0×e^-0.00057t (t/h), k_1/2= 1216(h).The reaction mechanism was hypothesized to be a ping-pong ter-ter reaction with inhibition by vinyl acetate. The initial rate equation for the asymmetric transesterification is: The parameters of the equation were calculated: V_m=112.06 mmoll^-1h^-1, K_mA=42.72 mmoll^-1, K_mBR=135.38 mmoll^-1, K_iA=1076.24 mmoll^-1.