RESOLUTION OF ENANTIOMERS OF A NOVEL THROMBOXANE SYNTHETASE INHIBITOR BY HPLC ON A CHIRAL STATIONARY-PHASE

DP-1904, a novel thromboxane synthetase inhibitor, has an assymmetric center in its molecule, and is used clinically as a racemate. An HPLC method is described for separating the enantiomers of DP-1904 and its methyl ester using a cellulose-based chiral stationary phase (Chiralcel OD). Resolution of the DP-1904 enantiomers was achieved using hexane-ethanol-formic acid (70:30:0.5) as a mobile phase, where, however, tailing of peaks of the enantiomers was observed. The base-line separation with sharp, well-defined peaks of the enantiomers of DP-1904 methyl ester was attained using ethanol-hexane (1 : 1) as a mobile phase. The optical purity of the analytical reference compounds, R-(+)- and S-(-) -DP-1904, which were prepared by fractional recrystallization of a synthetic intermediate, were determined after their conversion to the corresponding methyl esters. The enantiometric excesses of R-(+)- and S-(-) -DP-1904 were 98.5% and 97.1%, respectively.