Design and synthesis of naphthalene-based chiral strong cation exchangers and their application for chiral separation of basic drugs

Abstract

In continuation of our efforts to synthesize a highly dedicated strong cation exchanger, we introduce four chiral stationary phases based on a laterally substituted naphthalene core featuring chiral 2-aminocyclohexansulfonic acid as the chiral cation-exchange site. The selectors were modified with two different terminal units, which enabled immobilization to the silica support by thiol-ene radical reaction or azide-yne click chemistry. The chromatographic parameters of these chiral stationary phases were determined using a set of chiral amines, mainly from the family of β-blocker pharmaceuticals. The chiral stationary phases immobilized by means of click chemistry were found to be superior to those possessing the sulfide linker to the silica support. The chromatographic results and visualization of density functional theory-calculated conformations of the selectors hint at a combination of a steric and electronic effect of the triazole ring in the course of chiral resolution of the target analytes.

Keywords: basic pharmaceuticals; chiral cation exchanger; chiral separation; chiral stationary phase; liquid chromatography.