Liquid chromatographic resolution of 2-hydroxycarboxylic acids on a new chiral stationary phase derived from (S)-leucine

Enantiomers of racemic 2-hydroxycarboxylic acids have been resolved as their O-ethoxycarbonyl pi-basic anilide derivatives on a new chiral stationary phase (CSP) derived from N-(3,5-dinitrobenzoyl)leucine N-phenyl N-alkylamide and the resolution results have been compared with those on various commercial pi-acidic CSPs. The resolution results demonstrate that the new CSP derived from N-(3,5-dinitrobenzoyl)leucine N-phenyl N-alkylamide is most effective among the five CSPs tested for the resolution of 2-hydroxycarboxylic acid derivatives. In order to elucidate the chiral recognition mechanism exerted by the new CSP, the resolution of slightly differently modified derivatives of 2-hydroxycarboxylic acids on the new CSP has been investigated. Based on the resolution results, a chiral recognition mechanism utilizing three simultaneous interactions such as the face to face pi-pi interaction and the two hydrogen bonding interactions between the CSP and the more retained enantiomer of the analyte has been proposed.