Preparation And Chiral Recognition Of Novel Polysaccharide Derivatives-Based Chiral Stationary Phases

Due to the urgency of separation of chiral drugs, enantiomer separation has attracted great concerns in the field of chiral synthesis and analysis. Liquid chromatography chiral stationary phase (CSV) is an efficient, fast, and accurate method for enantiomer separation. The development of CSPs for high performance liquid chromatography (HPLC) is of great significance for the design, synthesis, and pharmacological research of new drugs, and also it is the main topic of our research. Coated and bonded phases are two major forms of CSPs. Exhibiting high chiral recognition to a wide range of chiral compounds, those coated-type polysaccharide derivatives-based CSPs appear to be highly useful. The novel polysaccharide derivative-based CSPs were prepared and their chiral recognition in HPLC was evaluated in the dissertation.In the first part, coated CSPs based on tris(3-trifluoromethylphenylcarbamate) of amylose and cellulose were prepared for HPLC enantioseparations. The obtained derivatives were characterized by FT-IR spectrum and elemental analysis, and their performances were evaluated by eight pairs of racemates using hexane-2-propanol as mobile phase. It was found that though compared with the most widely used, commercially available polysaccharide-based CSPs, Chiralpak AD and Chiralcel OD, utilizing tris(3,5-dimethylphenylcarbamates) of amylose and cellulose as the chiral selector, respectively, the obtained CSPs exhibited lower enantioseparation, cellulose tris(3-trifluoromethylphenylcarbamate)-based CSP exhibited characteristic enantioseparation and some chiral compounds were better resolved on this CSP than on Chiralcel OD. The chiral recognition abilities of the obtained CSPs were increased with the decrease of the portion of isopropanol in the mobile phase and relatively high enantioseparation was obtained under the mobile phase of hexane-isopropanol (95:5, v/v). The obtained amylosic phase demonstrated slightly higher chiral resolving ability than the cellulosic one for the test racemates. In addition, it was revealed that the enantioseparations of the cellulosic and amylosic CSPs were complementary.In the second part, A series of8regioselective substituted amlose derivatives with three different substituents at2-,3-, and6-positions of the glucose unit were prepared. They were characterized by FT-IR spectrum,1H NMR spectrum, and elemental analysis, and their performances were evaluated. The influences of mobile phase polar additives and concentration on enantioseparations were studied. It was found that all the obtained derivatives demonstrated characteristic chiral enanitoseparation. The chiral recognition abilities of the obtained CSPs were increased with the decrease of the mobile phases polarity and affected by the nature and location of the substituents. Compared with Chiralpak AD, one of the most efficient CSPs, the obtained amylose derivatives showed comparable or higher chiral recognition ability for some racemates. All the tested racemates could be separated on amylose2-benzoyl-3-(4-methylphenylcarbamate)-6-(3,5-dichlorophenylcarbamate), which appeared to be a very useful CSP with wide versatility.