Synthesis and application of chitosan thiourea derivatives as chiral stationary phases in HPLC

Abstract

Chitosan 2-thiourea derivatives with various substituents, including 3-(methylthio)propyl, phenyl, octyl and ethoxycarbonyl, at the 2-position of the glucosamine skeleton were prepared via isothiocyanates with the above substituents. The obtained chitosan 2-thiourea derivatives without ethoxycarbonyl were then esterified to develop a new series of chitosan 2-thiourea-3,6-diphenylcarbamate derivatives. The enantioseparation properties of the obtained chitosan derivatives were examined by high-performance liquid chromatography (HPLC). These results demonstrated that these chitosan 2-[3-(methylthio)propylthiourea]-3,6-diphenylcarbamate derivatives showed attractive chiral recognition abilities, especially for dihydropyridine calcium antagonist racemates. This result was probably attributed to the fact that the 2-thiourea substituents of this series of chitosan derivatives, as well as the 3,6-phenylcarbamate substituents, provided more favorable sites, which evidently enhanced the interactions between the enantiomers and the chitosan derivatives. The mechanism involved in the enantioseparation of the chitosan 2-[3-(methylthio)propylthiourea]-3,6-diphenylcarbamate derivatives was further discussed by molecular docking simulation.