Chemoenzymatic deracemization of chiral secondary alcohols: Process optimization for production of (R)-1-indanol and (R)-1-phenylethanol

摘要

A process for preparing chiral secondary alcohols by chemoenzymatic deracemization was optimized. First, the transesterification process of 1-indanol and 1-phenylethanol with vinyl acetate as the acyl donor was optimized using lipase Novozym 435 as biocatalyst. The effects of acyl donors, substrate concentration, solvent type, and enzyme amount on activity and enantiosellectivity of the said transesterification were investigated. Second,on the basis of the optimized conditions, an efficient biocatalytic resolution system was established with high selectivity, where volumetric productivity of the reaction against (R)-1-indanol and (R)-1-phenylethanol reached 529 and 198 g L-1 d(-1), respectively, during reuse of the enzyme in repeated-batch transesterification reactions. After 10 batches of the reaction, the enzyme still remained stable. Finally, (R)-1-indanol and (R)-1-phenylethanol were obtained in 95 % and 97 % ee and in 67 % and 71 % isolated yields from the corresponding resolution mixture, through an in situ Mitsunobu inversion of the unreacted alcohols followed by chemical hydrolysis of (R)-acetates.