Studies On The Preparation And Chiral Recognition Of Novel Chitosan-based Chiral Stationary Phases

High-performance liquid chromatography with chiral stationary phases(HPLC-CSPs)has become the most efficient and popular technique for chiral separation and analysis.The preparation of CSPs with a high chiral recognition ability is the key of this technique,and till now,more than 200 CSPs have been commercialized.Among the CSPs developed by far,polysaccharide-based CSPs,especially those utilizing phenylcarbamate derivatives of cellulose and amylose,are well-known to exhibit high chiral recognition to more than 90%of racemic compounds.On the other hand,chitosan has the similar structure to those of chitin and cellulose,except for the 2-position of glutamine unit.Preparation of chitosan-based CSPs with quite different chiral recognition ability from that of cellulose derivatives may be possible due to this structural difference.However,the study on the synthesis of chitosan derivatives have been very limited so far,and the systematical investigation on the structure and chiral recognition ability of chitosan derivatives is still not reported yet.Based on this fact,the synthesis and chiral recognition ability of novel chitosan derivatives bearing different groups were performed in this study,and their chiral recognition mechanism on the molecular level is further explored.Firstly,N-deacetylation of the chitosan was carried on,several series of chitosan derivatives bearing different groups(including phenyl ureas and phenylcarbamates)were then synthesized by“one pot”procedure,and their structures and properties were characterized by ~1H NMR,IR spectroscopy and elemental analysis.Then,the coated-type CSPs based on the obtained chitosan derivatives were prepared by coating on the surface of aminopropyl silica gel through coating method,and,and the coating efficiency of CSPs was analyzed by thermogravimetry analysis(TGA).Finally,the chiral recognition abilities of the chitosan derivatives were evaluated through enantioseparation of ten racemates based on the novel CSPs by HPLC.The effect of nature,number and position of substituents on the secondary structure and chiral recognition ability of chitosan derivatives was systematically investigated,and the chiral recognition mechanism from the molecular level was further exploredIt indicated that chitoan derivatives bearing 3,5-dimethyl or 3,5-dichlorophenylcarbamte substituents exhibited higher chiral recognition ability,and the chiral recognition ability of novel chitosan derivatives can be significantly influenced by substituents at three positions of the glutamine unit.The introduction of both electron-withdrawing or electron-donating groups can enhance the chiral recognition of chitosan derivatives.The better stereoregularity,the higher chiral recognition ability.the former exhibited higher chiral recognition ability to some racemates than some commercial chiral columns.Moreover,the coated-type chitosan-based CSPs can apply some polar solvents as eluents for HPLC,which exhibit prominent advantage in the resolution of some chiral compounds with poor solubility.