Lipase-catalyzed remote kinetic resolution of citalopram intermediate by asymmetric alcoholysis and thermodynamic analysis.
Lipase-catalyzed remote resolution of the tertiary alcohol, citalopram intermediate (diol acetate), has been achieved. The chiral discrimination was obtained by the Novozym435-catalyzed alcoholysis of the primary hydroxyl ester which was four bonds away from the center. The influence of acyl acceptor structure and the organic solvents on the reaction rate and enantioselectivity were investigated. Based on the thermodynamic analysis, the difference of activation free energy between the two enantiomers which dominated the enantioselectivity was significantly affected by the organic solvents, while the acyl acceptor showed less effect. In addition, the enantiomer discrimination was driven by both the difference of activation enthalpy and activation entropy. The thermodynamic analysis provides further insights into the prediction and optimization of enantioselectivity and reaction rate in remote resolution.
Institute of Bioengineering, Department of Chemical and Biochemical Engineering, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, 361005, China. szwang@xmu.edu.cn
Shi-Zhen
SZ
Wang
Jian-Ping
JP
Wu
Gang
G
Xu
Li-Rong
LR
Yang
D015283:Citalopram / Q000737:chemistry*; D004800:Enzymes, Immobilized; D005656:Fungal Proteins; D007700:Kinetics; D008049:Lipase / Q000737:chemistry*; D008956:Models, Chemical; D013816:Thermodynamics
D004800:Enzymes, Immobilized; D005656:Fungal Proteins; D015283:Citalopram; C093667:Novozyme 435; D008049:Lipase