Epimeric N-substituted l-proline derivatives as chiral selectors for ligand-exchange chromatography

Abstract

Mainly N-alkyl derivatives of l-proline have proved useful as chiral selectors, particularly in the field of chiral ligand-exchange chromatography (CLEC). This paper describes the synthesis of new N-alkyl derivatives of l-proline, containing a second centre of chirality, and their immobilization on silica gel. The applicability of these chiral stationary phases in CLEC with either copper(II) or nickel(II) as complexing ion was investigated. Particular attention was paid to the effects of the organic modifier, buffer concentration and pH on stereoselectivity and retention. The aim of this study was also to elucidate the influence of the second centre of chirality, which contains a π-basic, space-filling phenyl group and a polar amide function, on enantioseparation and elution order. Based on simple molecular modelling studies, recognition mechanisms and the possibility of the amide oxygen coordinating with either copper(II) or nickel (II) are discussed. Both epimeric chiral selectors (either R, S- or S, S-configuration) resolved the enantiomers of various amino acids and derivatives thereof.