A high-performance chiral selector derived from chitosan (p-methylbenzylurea) for efficient enantiomer separation.

N-Methoxycarbonyl chitosan was prepared by selectively modifying the amino group at the 2-position of chitosan with methyl chloroformate, which was further functionalized with p-methylbenzylamine to produce chitosan (p-methylbenzylurea). Then, the hydroxyl groups at the 3- and 6-positions of the glucose skeleton were modified with various phenyl isocyanates, affording a series of chitosan 3,6-bis(arylcarbamate)-2-(p-methylbenzylurea)s, which were characterized and proposed as chiral selectors for enantiomer separation. Nineteen racemates, most of which are drugs or intermediates for drugs, were selected as the model analytes to evaluate the enantioseparation performance. The structure-performance relationship of the chiral selectors was investigated in detail. It was found that the methyl-substituted chiral selectors possessed more preferable enantioseparation performance compared with the chloro-substituted ones, and the chiral selectors containing a methyl substituent at the 4-position of the benzene ring showed the best chiral recognition and separation ability with 17 racemates being recognized and 13 racemates being baseline separated. The prepared chiral separation materials derived from these chiral selectors exhibited favorable solvent tolerance towards ethyl acetate, acetone, chloroform and a low proportion of tetrahydrofuran in normal phase. To sum up, this work provided a useful reference for the design and preparation of high-performance chiral separation materials for efficient enantiomer separation.

Structural dependence on the property of chiral stationary phases derived from chitosan bis(arylcarbamate)-(amide)s.

The goal of present study was to investigate the structural dependence of chitosan derivatives on enantioseparation and mobile phase tolerance of the corresponding chiral packing materials for liquid chromatography. Hence, a series of chitosan bis(arylcarbamate)-(n-pentyl amide)s and the related chiral stationary phases (CSPs) were prepared from chitosans with different molecular weights. Because of the H-bond formed via CH3-π interaction, the CSP bearing methyl substituent exhibited high tolerance than the ones bearing dichloro substituents. The CSP derived from the chitosan bis(3,5-dichlorophenylcarbamate)-(n-pentyl amide) with a higher molecular weight possessed high tolerance to mobile phases, whereas the enantioseparation capability of this CSP was not as good as that of the one prepared from the chitosan derivative with a lower molecular weight. Therefore, enantioseparation capability and mobile phase tolerance have to be counterbalanced in designing chiral selectors for the CSPs derived from chitosan bis(arylcarbamate)-(amide)s.

Enantioseparation characteristics of the chiral stationary phases based on natural and regenerated chitins.

Natural and regenerated chitins were derivatized with 3,5-dimethyphenyl isocyanate. The corresponding chiral stationary phases were prepared by coating the resulting chitin derivatives on 3-aminopropyl silica gel. The swelling capacity of the chitin derivatives, enantioseparation capability, as well as eluents tolerance of the chiral stationary phases were evaluated. The results demonstrated no remarkable difference in enantioseparation capability between natural and regenerated chitins based chiral stationary phases. The similar enantioseparation characteristics of two chiral stationary phases could be understood by comparing the IR spectra of related chitin derivatives. The one of the two chiral stationary phases prepared by coating the chitin derivative with a lower molecular weight generally provided better enantioseparations. All chiral stationary phases can work in 100% chloroform, 100% ethyl acetate, 100% acetone, and the mobile phases containing a certain amount of tetrahydrofuran. The chiral stationary phase prepared from the chitin derivative with the highest swelling capacity exhibited better enantioseparations than others. This chiral stationary phase was damaged by flushing with 100% tetrahydrofuran, however, the enantioseparation capability was recovered again after the column was allowed to stand for 1 month. Furthermore, the recovered chiral stationary phase provided better enantioseparations for some chiral analytes than before.