Synthesis of substituted phenylcarbamates of N-cyclobutylformylated chitosan and their application as chiral selectors in enantioseparation

Abstract

The goal of this study was to develop new chiral stationary phases (CSPs) with high chiral recognition capability and high compatibility with the so-called "nonstandard solvents". Seven new chitosan bis(phenylcarbamate)-(N-cyclobutylformamide) derivatives were synthesized from chitosan with high degree of deacetylation as a starting material. The corresponding chiral stationary phases (CSPs 1-7) were prepared with the chitosan derivatives as chiral selectors (CSs). The enantioseparation capability of CSPs 1-7 was evaluated by high performance liquid chromatography with nineteen analytes. In comparison with the CSPs of cellulose tris(3,5-dimethylphenylcarbamate) (CDMPC) and amylose tris(3,5-dimethylphenylcarbamate) (ADMPC), the prepared CSPs generally demonstrated excellent enantioseparation capability, particularly for the CSP derived from chitosan bis(3-chloro-4-methylphenylcarbamate)-(N-cyclobutylformamide). Moreover, the CSPs in the present study could separate some analytes better, making them complementary for enantioseparations with the CSPs of CDMPC and ADMPC. The tolerability of the CSP with the best enantioseparation capability to organic solvents was investigated. The results showed that it could work in pure ethyl acetate, pure chloroform, and a normal phase containing 70% tetrahydrofuran, which are prevented from enantioseparation by the coating type CSPs of CDMPC and ADMPC. As these chitosan derivatives were almost insoluble in most organic solvents, the corresponding CSPs can work in a wide range of mobile phases. In addition, the influence of the position and electron effects of methyl and chloro groups introduced onto the CSs and the composition of mobile phases on enantioseparation was also discussed.

Chiral Stationary Phases for Liquid Chromatography Based on Chitin- and Chitosan-Derived Marine Polysaccharides

“…Other CSPs based on the substitution of the amine of chitosan with an alkyl moiety, prior to the derivatization of the hydroxyl groups with different isocyanates were described [68,70] In the same year, some bis-phenylcarbamate derivatives with different substituents in both phenylcarbamate and amine moieties (58)(59)(60)(61) were obtained by the same group (Table 5) [69]. The synthesized chitosan derivatives were coated on aminopropyl silica, and showed chiral recognition for the majority of the tested racemates.…”

“…Other CSPs based on the substitution of the amine of chitosan with an alkyl moiety, prior to the derivatization of the hydroxyl groups with different isocyanates were described [68,70] 1.10 A A -Hex/2-PrOH (90:10 v/v); B -Hex/EtOH (90:10 v/v); C -Hex/2-EtOH/MeOH (90:5:5 v/v/v), 1.0 mL/min. Coated with DMF on APS.…”

“…Other CSPs based on the substitution of the amine of chitosan with an alkyl moiety, prior to the derivatization of the hydroxyl groups with different isocyanates were described [68,70]. Actually, Feng et al, prepared several bis-4-methylphenylcarbamates with different alkyl moieties linked in the amine group of chitosan (62-64) ( Table 5) [68].…”

“…Furthermore, Zhang et al, developed several CSPs based on N-cyclobutylformilated chitosan derivatives (65-71) ( Table 5) [70]. These CSPs showed good chiral recognition abilities, specially the CSPs comprising the chitosan-derivatives 66, 67 and 68, being able to recognize most of the tested racemates.…”

“…These CSPs showed good chiral recognition abilities, specially the CSPs comprising the chitosan-derivatives 66, 67 and 68, being able to recognize most of the tested racemates. Additional analysis were performed to evaluate the tolerability to other organic solvents, which showed no significant changes in the enantiorecognition abilities of the tested CSPs after being flushed with ethyl acetate (100%), chloroform (100%) and hexane/tetrahydrofuran (50/50, 40/60, 30/70 v/v) [70].…”