Evaluation of Pirkle-type chiral stationary phases by liquid and supercritical fluid chromatography: Influence of the spacer length and the steric hindrance in the vicinity of the stereogenic centre

Abstract

The scope of applications of novel chiral stationary phases (CSPs) derived from ( S)-phenylalanine or ( R)-phenylglycine and bearing a long spacer in normal-phase liquid chromatography is reviewed with regard to the similar corresponding commercially available brush-type CSPs. The parameters studied were the spacer length and the steric hindrance in the vicinity of the stereogenic centre. The direct separation of β-blockers in supercritical fluid chromatography (SFC) was also carried out in order to elucidate the influence of the steric decompression. The chromatographic properties of one of the novel CSPs and the commercially available CSP ChyRoSine-A, exhibiting both a long spacer and a weak steric hindrance in the vicinity of the stereogenic centre, were compared. The design and synthesis of three novel CSPs derived from phenylalanine or phenylglycine and starting from the concept of ChyRoSine-A allowed an optimized CSP to be proposed. This CSP possesses both reduced steric hindrance in the vicinity of the stereogenic centre and a long spacer. Its main advantage is that it combines the fields of application of various CSPs (DNBPG, ChiraChrom A1, ChyRoSine-A). In addition, this CSP allows the resolution of β-blockers, where both DNBPG and ChiraChrom A1 fail.