Development of novel chiral stationary phases derived from 18C6H<SUB>4</SUB> and a mobile-phase additive used in Crownpak CR(+)for the enantiomer separation of hydrophobic amino compounds

Abstract

Enantiomers often differ in pharmacological activity. Usually, only one of the various isomers fully contributes to therapeutic action, and the others do not. The separation of enantiomers is a subject of great interest because the antipode of a chiral drug is regarded as being an impurity from the view-point of quality control. Recently, chromatographic techniques, especially high-performance liquid chromatography with chiral stationary phases(CSPs), have been extensively used to achieve direct enantiomer separation. Various kinds of CSPs are commercially available. In this study, (1)the author designed and prepared novel CSPs(CSP-18C6I, II, III) which immobilized chiral crown ether ((+)-18-crown-6 tetracarboxylic acid). Then, the CSPs(18C6 series) were applied to the enantiomeric separation of amino acids, aminoalcohols and some hydrophobic amino compounds, which were them enantioseparated successfully. (2)Studies of the chiral-recognition mechanism of 18C6H4 using NMR and crystalline X-rays were performed and explained. (3)A modification(the addition of metal cations or cyclodextrin) of the mobile phase used in Crownpak CR(+), where hydrophobic chiral crown ether was dynamically coated on an ODS column, was investigated. A fast analysis of hydrophobic amino compounds was accomplished using this method.