Enantioselectivity of Hydrogen-Bond Association in Liquid-Solid Chromatography

Abstract

Liquid chromatographic resolutions of enantiomers induced by molecular associations whose main driving force is the action of weak hydrogen bonds are described. The hydrogen-bond association potential was first demonstrated through the optical resolution of racemic N-acylated amino acid esters using a chiral stationary phase (CSP) (N-acyl-L-valylamino)propyl silica gel. Following this preliminary study, application was made of the chiral mobile phase additive (CMPA) on which the fundamental structure of the chiral graft of CSP is reproduced, to the resolution of the above solute enantiomers in liquid-solid chromatography. The addition of N-acetyl-L-valine tert-butylamide to the nonaqueous mobile phase solvent of a silica gel column successfully brought about this optical resolution; by this method, a novel and more effective chiral resolving agent was found. Two types of chiral additives derived from a chiral skeleton (R,R)-tartaric acid were found capable of resolving various kinds of enantiomers, such as dialkyl tartrate and dialkyl tartramide. Of these two, the latter in particular, having an isopropyl substituent, led to a wide range of resolution of enantiomers of the following categories: α- and β-hydroxycarboxylic acid, β-hydroxy ketone, β-amino alcohol, α-amino acid, α-hydroxy ketoxime derivatives, and bi-β-naphthol. This occurred when the enantiomers, except β-hydroxy ketones, α-hydroxy ketoximes, 1,2-diols and bi-β-naphthol, were derivatized so as to respond to the hydrogen bonding sites of the additive molecules.