Efficient Synthesis Of New Fluorinated Beta-Amino Acid Enantiomers Through Lipase-Catalyzed Hydrolysis

An efficient and novel enzymatic method has been developed for the synthesis of beta-fluorophenyl-substituted beta-amino acid enantiomers through lipase PSIM (Burkholderia cepasia) catalyzed hydrolysis of racemic beta-amino carboxylic ester hydrochloride salts 3a-e in iPr(2)O at 45 degrees C in the presence of Et3N and H2O. Adequate analytical methods were developed for the enantio-separation of racemic beta-amino carboxylic ester hydrochlorides 3a-e and beta-amino acids 2a-e. Preparative-scale resolutions furnished unreacted amino esters (R)-4a-e and product amino acids (S)-5a-e with excellent ee values (>= 99%) and good chemical yields (>48%).