Multi-interaction (substituted-phenylcarbamate)-hydroxypropyl-β-cyclodextrin chiral stationary phases for liquid chromatography

Background

(Substituted-phenylcarbamate)-β-cyclodextrin (β-CD) chiral stationary phases (CSPs) showed high enantioselectivity and complementary capabilities compared to polysaccharide-based CSPs in liquid chromatography. Most of the previous works were about preparation and application of (substituted-phenylcarbamate)-β-CD, while very limited works was available reporting modified hydroxypropyl-β-CD (HP-β-CD) used for CSP. As matter of fact, HP-β-CD was more frequently used than native β-CD as chiral selector in many chiral separation techniques. Therefore, it was great of significance to investigate preparation of multi-interaction (substituted-phenylcarbamate)-HP-β-CD CSPs and its application in chiral separation.

Results

Three new multi-interaction (substituted-phenylcarbamate)-HP-β-CD CSPs were prepared and investigated, including (3-chloro-4-methylphenylcarbamate)-HP-β-CD CSP, (4-chloro-3-methylphenylcarbamate)-HP-β-CD CSP and (5-chloro-2-methylphenylcarbamate)-HP-β-CD CSP. The structure and morphology of the three chiral selectors as well as their stationary phase were characterized by ¹H NMR spectra, elemental analysis, infrared spectroscopy, scanning electron microscopy and thermogravimetric analysis. Degree of substitution, stability, repeatability and reproducibility of the (substituted-phenylcarbamate)-HP-β-CD CSPs were investigated. A total of 56 racemic compounds were examined on the three (substituted-phenylcarbamate)-HP-β-CD CSPs using reversed-phase elution mode. It was found that enantioselective recognition capability of the three (substituted-phenylcarbamate)-HP-β-CD CSPs was greatly improved compared with that of traditional HP-β-CD CSPs, which was demonstrated by the number of successful enantioseparated racemates and increased enantioseparation efficiency. Applications of the three CSPs in high performance liquid chromatographic enantioseparations indicated that each of them showed different enantiorecognition ability toward different type of racemic structures, which showed high complementary enantiorecognition ability with traditional β-CD-based CSPs.

Significance

An efficient one-pot reaction strategy for synthesis of (substituted-phenylcarbamate)-HP-β-CD CSPs was developed. It was found that enantiorecognition and peak resolutions (Rs) were greatly improved compared with traditional HP-β-CD CSP and β-CD CSP. The improved chiral separation performance of multi-interaction HP-β-CD CSPs was demonstrated, providing valuable insights for the development of efficient chiral separation methods while expanding the potential applications of HP-β-CD in chiral liquid chromatography.