ASSIGNMENT OF ABSOLUTE-CONFIGURATION AND OPTICAL PURITY DETERMINATIONOF (R)-ECONAZOLE AND (S)-ECONAZOLE NITRATE BY ENANTIOSELECTIVE HPLC -METHOD DEVELOPMENT AND APPLICATION

A method is described for the synthesis and optical purity determinati on of (-)-(R)- and (+)-(S)-econazole via the optically pure intermedia tes, (R)- and (S)-imidazolylethanol, which are available by chromatogr aphic resolution or by fractional crystallization of diastereomeric O, O'-disubstituted (R;R*)- or (S*;S*)-tartaric acid monoesters of the p arent imidazolylethanol racemate. Furthermore, this method allows the chromatographic assignment of the absolute configuration of the chiral center of the imidazolylethanol enantiomers and consequently of econa zole enantiomers. In addition, a direct liquid chromategraphic enantio separation method for the determination of the optical purity of (R)- and (S)-econazole and other chiral imidazoles on a protein type CSP (O VM) is described and applied to confirm chromatographically the absolu te configuration evaluations. (C) 1994 Wiley-Liss, Inc.