Preparation And Evaluation Of Chitosan-4-Methyl Phenylcarbamate-urea Chiral Stationary Phases

The separation and measurement of chiral compounds, as well as the preparation of chiral drugs with higher optically pure, which have played a particularly important role in some prosperous areas such as medicine, toxicology, clinical analysis and pharmaceutical industries and have had the broad market development prospects. In the numerous chiral separation technology of optical isomers, HPLC chiral stationary phase method has been one of the most direct, easiest and the most effective ways to separate and obtain the single enantiomers. Moreover, cellulose derivatives and amylose derivatives have been widely used because of its high load, excellent chiral separation ability and suitability for the separation of some enantiomers. In order to obtain the chiral stationary phase with much stronger separation ability and broader universality, people are still continuously studying and manufactoring a novel chiral stationary phase.As the product of deacetylation of chitin, chitosan is a natural basic polysaccharide with a linear type, which is the most abundant optically active polymers and is characterized by the good biocompatibility, non-toxic side effects as well as its own optical activity. Moreover, inherent chiral chitosan can be conveniently chemically modified at the amino and a hydroxyl groups to prepare for a novel chiral stationary phase.In this paper, the commercial chitosan with acetyl group at 2 position of glucosamine ring was treated with 50% aqueous NaOH, 4-methylphenyl isocyanates as derivatization reagent, chitosan-4-methylphenyl carbamate-urea derivatives was synthesized and used as the chiral stationary phase(CSP1) for high-performance liquid chromatography(HPLC) after coating on the 5?m aminopropyl silica gel. The chiral recognition ability of the obtained CSP1 was evaluated.The synthesis involved the protection and deprotection of 6-position using triphenylmethyl chlorides, which could predominantly react with 6-OH of chitosan, then a novel chitosan-methyl phenyl carbamate-chloropheny carbamate-urea derivatives was synthesized and used as chiral stationary phase(CSP2) for HPLC after coating on the 5?m aminopropyl silica gel to improve the ability of chiral recognition of CSP1. The chiral recognition ability of the CSP2 was evaluated using 13 racemates at the condition of normal phase mode, and the CSP2 showed a perfect chiral recognition and separation capability.Another novel chitosan-phenyl carbamate-methylphenyl carbamate-urea derivatives was synthesized and used as chiral stationary phase(CSP3) for HPLC after coating on the 5?m aminopropyl silica gel with the same ways of CSP2. The chiral recognition ability of the CSP3 was evaluated using the same 13 racemates at the condition of normal phase mode. Compared with CSP1, the result showed that the chiral recognition ability of CSP3 was less than the CSP1, but the resolution of the racemates obtained separation on CSP3 was higher than that on the CSP1.The column temperature played an important role in the HPLC chiral separation process. In order to have a deeper understanding of the mechanism of chiral recognition, the thermodynamic parameters of the solute adsorption separation process could be obtained by establishing the relationship between the chromatographic parameters and the column temperature. In this paper, the influence of the column temperature on the chiral recognition ability of chiral stationary phases was investigated. The result showed that the chiral separation process was driven by the enthalpy.