Use of Aspergillus oryzae protease for the resolution of -hydroxy acids by enantioselective ester hydrolysis

The enzymatic hydrolysis of esters of -hydroxy acids as non-amino acid substrates for microbial proteases was investigated. The methyl esters of 3-phenyllactic acid and its ring-substituted derivative were hydrolyzed with excellent enantioselectivities (E>110) using Aspergillus oryzae protease to give the (S)-acids. By contrast, only low enantioselectivities (E∼1) were obtained with the esters of mandelic acid. A gram-scale resolution of 3-phenyllactic acid was achieved by adopting this procedure, to afford the (S)-acid with 96% e.e. in 67% yield after recrystallization.