Conformational and temperature effects on separation of stereoisomers of aC3,C4-substituted beta-lactamic cholesterol absorption inhibitor on amylose-based chiral stationary phases

A direct liquid chromatography method was developed for the diastereo- and enantiosetective analysis of a C3, C4-substituted beta -lactamic hypolipode mic agent (SCH 48461) and its stereoisomers on two commercially available a mylose-based chiral stationary phases (CSPs), namely, Chiralpak AS and Chir alpak AD. The mobile phase composition (type and content of alcoholic modif ier) was considered to achieve baseline resolutions in a single chromatogra phic run. In order to investigate the influence of molecular flexibility on chiral recognition process. P-lactams were ring-opened and converted into beta -amino esters derivatives. Thermodynamic parameters associated with ad sorption equilibria between acyclic and cyclic stereoisomers and CSPs were calculated from chromatographic runs at various temperatures. (C) 2001 Else vier Science B.V. All rights reserved.