Development And Application Of Novel Dupex Cyclodextrin Stationary Phases Via ‘Click' Chemistry

High optical purity of biologically active compounds, especially the acquisition of high optical pure chiral drugs has become a focus of research in the field of pharmaceutical research. In recent years, with the rapid development of chiral drugs‘ market, the demand of enantiopure chiral drugs as well as the concerns on pharmacology and toxicology are increasing, the development of enantioseparation techniques has been facing more and more challenges. Direct enantioseparation by chiral stationary phases(CSPs) using HPLC technique has become the most common methodology for separation of chiral drugs due to its high selectivity, mild separation condition and broad application. Therefore,the development of novel stable and powerful CSPs is of great importance. Cyclodextrins(CDs) are non-reducing naturally occurring oligosaccharides with a unique hydrophobic cavity. This character endows CDs with a special capacity in accommodating a large variety of compounds, which results in their comprehensive applications in chiral separationIn order to break bottleneck in the development of CD-CSPs, the current thesis reports the successful construction of a bridged CD dimers in a tandem-inverted orientation onto silica particles via a surface-up click strategy to realize a new generation of bilayer CD-CSP materials.(1) The native tandem-inverted triazole-bridged duplex CD-CSP(DCDCSP) material was constructed via a surface-up ?click‘ approach. The synergistic effect of the duplex CDs was evidenced by the superior enantioresolution ability toward selected chiral compounds and the enhanced adsorption ability toward hesperetin. The enantioselectivities of dansyl amino acids and arylcarboxylic acids were promoted by 10–20%, while the resolutions of some aryl carboxylic acids were significantly increased from 0 to 3.5 and beyond. Adsorption experiments of hesperetin revealed the binding ability of the single layer CD-CSP.(2) On the basis of our previous work, native and perphenylcarbamoylated-?-CD were successively immobilized onto silica surface via a two-step click approach to fabricate a novel ?native-phenylcarbamoylated‘ bilayer CD-CSP(DNPCDCDP). The hybrid bilayer CD-CSP can provide multiple interaction sites such as H-bonding(-OH, C=O,-NH-), steric effects, ?-?,dipole–dipole and inclusion complexation interactions, which helps to broaden the CSP‘s enantioselectivity profile and enhance the enantioselectivity to some specific analytes. A group of enantiomer pairs such as isoxazolines, bendroflumethiazide, indoprofen, diperodon, fenoterol, atropine and styrene oxide can be baseline or partially separated on this CSP under reversed phase high performance liquid chromatography(RP-HPLC). The selectivity and resolution of 4NPh-OPr reached 5.25 and 13.97, which is an exciting achievement for the enantioseparations by CD-CSPs.In this thesis, we have developed an effective approach for the fabrication of novel bilayer CD-CSP materials which providing a simple and practical approach to design and synthesize novel functional materials with cooperative CD dimers on surfaces. We investigated the chiral chromatography performance of the prepared CD-CSPs towards various drug enantiomers, establishing the optimal separation conditions as well as providing a reference for the rapidly screening of drug enantiomers.