Chemoenzymatic approach to optically active phenylglycidates: resolution of bromo- and iodohydrins

Abstract

Enantiomerically enriched phenylglycidates, precursors of the taxol C-13 phenylisoserine side chain and diltiazem, were prepared by kinetic resolution of anti-2-bromo-3-hydroxy- and anti-3-hydroxy-2-iodophenylpropanoates to provide enantioriched (2 R,3 R)- and (2 S,3 S)-halohydrins. The bulkiness and inflexibility of bromo and iodo groups in halohydrins have made them inaccessible to the active site of most of the lipases utilized for the hydrolysis of their acyloxy derivatives. In a set of 22 hydrolases screened herein, including native as well as commercial enzymes, only Aspergillus niger (Lipase AS, AMANO) could catalyze the hydrolysis with high enantioselectivity ( E = 176). The resolved halohydrins easily underwent transformation to the corresponding (2 S,3 R)- and (2 R,3 S)-phenylglycidates.