Highly enantioselective synthesis of arylaliphatic tertiary alcohols using mutants of an esterase from Bacillus subtilis

The kinetic resolution of a series of acetates of arylaliphatic tertiary alcohols was studied using recombinant esterase variants from Bacillus subtilis (BS2) expressed in E. coli. Highest enantioselectivities (E > 100) were achieved in the synthesis of 1,1,1-trifluoro-2-phenylbut-3-yn-2-ol and three para-substituted analogues using BS2 mutant G105A. With mutant E188D only two compounds were converted with E > 100. For a thiophene analogue or compounds with small variations in the aliphatic chain substantially lower conversions and/or enantioselectivity were observed, which also varied with the BS2 variant used. Thus, small changes in the substrate structure and point mutations in the esterase had a remarkable influence on both activity and enantioselectivity.