title: Chiral resolution of racemic p-methylsulfonylphenyl serine ethyl ester with lipases: the mechanism of side reaction and its suppression.
abstract: The D-threo form of p-methylsulfonylphenyl serine ethyl ester (MPSE) is a key intermediate for the synthesis of florfenicol. In this study, chiral resolution of DL-threo-p-MPSE with lipases was investigated. Among a series of lipases, Novzyme 435 was the best to resolve DL-threo-p-MPSE with the conversion rate of 36.83% and ee value of 35.13%. To improve the conversion rate and ee value, a number of byproducts were identified and characterized using reverse-phase HPLC, normal-phase HPLC, (1)H NMR, and LC-MS when threo-p-MPSE was hydrolyzed by lipases in organic medium. Mechanisms of generating main byproducts are proposed, and a suppressing method is provided. The results showed that byproduct p-methylsulfonyl benzaldehyde serves as the key intermediate during the whole side reaction process. It was also observed that threo-p-MPSE with a proper hydrolytic velocity served as a driving force to generate p-methylsulfonyl benzaldehyde and accelerated the side reactions. Finally, a feasible approach to suppress side reactions in enzymatic catalysis is offered. The conversion rate and ee value were greatly improved by 69.29 and 46.26%, respectively, using Zn(2+) compared to those without Zn(2+).
authors.affiliation: Institute of Fermentation Engineering, College of Biological and Environmental Engineering, Zhejiang University of Technology, Hangzhou 310014, People's Republic of China.
authors.forename: Rui
authors.initials: R
authors.lastname: Guo
authors.forename: Yong-Xian
authors.initials: YX
authors.lastname: Fan
authors.forename: Xiao-Long
authors.initials: XL
authors.lastname: Chen
authors.forename: Yin-Chu
authors.initials: YC
authors.lastname: Shen
mesh_terms: D002851:Chromatography, High Pressure Liquid; D002853:Chromatography, Liquid; D004952:Esters; D006863:Hydrogen-Ion Concentration; D008049:Lipase / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D013237:Stereoisomerism; D013450:Sulfones / Q000737:chemistry*; D013696:Temperature
chemical_list: D004952:Esters; D013450:Sulfones; D008049:Lipase