Synthesis Of Novel Cationic β-cyclodextrins For Enhanced Enantiomeric Separation Via Hydrogen-bonding In Capillary Electrophoresis

With the development and progress of medical technology, people require more chiral drugs as well as pay more attention to efficiency and side-effect of the chiral drugs. As a result, the separation of chiral drugs has become an important issue in current society. Capillary electrophoresis (CE) has been developed to be an effective method for the chiral separation with the advantages of high separation efficiency, rapid analysis process, convenient and so on. It has been reported that β-cyclodextrin and its derivatives are a class of commonly used chiral selectors in chiral capillary electrophoresis. Then, the design and modification of the chiral selector is outmost important to optimize the enantioseparation by CE.In this thesis, two new series of positively charged (3-cyclodextrins have been developed with their enhanced chiral selectivity evalulated via the construction of hydrogen-bonding in CE. All the products have been prepared with facile synthetic routes and structure fully confirmed with melting point detection,1H NMR、13C NMR、FT-IR or ESI-MS. Besides, chiral separation of Dns-aminos, a-hydroxy acids and carboxylic acids in CE were all effectively separated, and it contains two parts;(1) The first series are the mono substituted positively charged β-cyclodextrin:6A-(2-methoxyethylamonium)-6A-doxyl-β-cyclodextrin chloride (MEtAMCD) and6A-(4-methoxybutylamonium)-6A-doxyl-β-cyclodextrin chloride (MBuAMCD). Compared with the usual positively charged ammonium β-cyclodextrin, theses new β-cyclodextrins feature a methoxy group (-OCH3) as the terminal on the common alkyl chain, which could form hydrogen bonds with analytes to enhance the chiral separation process. In addition,’H NMR method has innovatively employed to study the complexation of the cyclodextrin and verify the effect of the hydrogen bond to chiral separation. As the chiral selector, chiral separation of Dns-aminos, a-hydroxy acids and carboxylic acids in CE was achieved. We also have investigated several factors which affect the chiral separation, such as the buffer pH, the CD concentration, temperature and voltage and so on.(2) The second series are disubstituted positively charged β-cyclodextrin:6A-ammonium-6c-butylimidazolium-β-cyclodextrin (AMBIMCD). The first hydroxyl of the cyclodextrin are disubstituted by ammonium and butylimidazolium group, then possess not only the features of ammonium β-cyclodextrins but also the merits of imidazolium β-cyclodextrins. Owing to this, they could be able to achieve good chiral separation for both of amino acids and other acid racemates. The two positively charged centers enabled good enantioseparation of the racemates in lower CD concentration. The amine group of this CD offer the possibility to form hydrogen bonds with a-hydroxy and phenoxyalkanoic acids, then better resolution can be obtained for these acids. At the same time, the obtained results of this dicationic CD are compared to its mono-imidazolium or ammonium-substitued counterpart CDs, which reflct that AMBIMCD has excellent enantioselectivities for the selected analytes.In summary, this thesis successfully prepared two series positively charged (3-cyclodextrins which constructed by oxygen and nitrogen atoms, each one has its good points in chiral separation. This research offers a plateform for the design of positively charged β-cyclodextrins with more excellent performance.