Simultaneous enantioseparation of flobufen and its diastereomeric metabolites on ULMO, a Pirkle type chiral stationary phase.

Abstract

Using normal-phase HPLC, the enantiomers of 4-(2',4'-difluorobiphenyl-4-yl)-4-oxo-2-methylbutanoic acid (flobufen) could be separated on Whelk-O1 (alpha = 1.34), ULMO (alpha = 1.08) and Chiralcel ODH (alpha = 1.33) chiral stationary phases. (R,R/S,S)- and (R,S/S,R)-5-(2',4'-difluorobiphenyl-4-yl)-3-methylfuran-2-one, the lactone of the 4-hydroxy metabolite could be completely separated on ULMO only. On the same CSP this 4-(2',4'-difluorobiphenyl-4-yl)-4-hydroxy-2-methylbutanoic acid could be separated in part (alpha = 1.06 and 1.12). Absolute configuration of the metabolites was established by NOE experiments.