Synthesis Of New β-Cyclodextrin Derivatives And Application For Separation Of Pharmaceutical Enantiomers

The existence of the chrial enantiomers is a universal phenomenon in nature, especially in the field of pharmaceutical chemistry. The separation of pharmaceutical enantiomers is one of the most attractive tasks in the modern Analysis Chemistry field. Because of the similar Physical-Chemical properties of two enantiomers, the separation becomes more difficult. Capillary electrophoresis (CE) has attained great acceptance mostly owing to its high separation efficiency, low sample and electrolyte consumpt- ion, and short analysis times etc.The use of chrial selectors in CE to affect the separation of enantiomers continues to be an imporant method for CE chrial separation. Successful chiral separation lies in choosing accurate chiral selector, current research is still focus on finding and synthesizing new chiral selectors.Cyclodextrins (CDs) including native and derivatized CDs became the most popular electrophoretic chiral selectors in CE. However, there are some physical-chemical limits of the native CDs for chiral separation in their solubility and molecular bonding ability etc. CD derivatives exhibit different properties compared to the native ones as follows:(1). Improved solubility;(2). Expanded binding cavity and the improved ability of coordi nation;(3). The charged CDs can separate uncharged and charged chiral drugs (especially the drugs of opposite charge )So the utilization of modified, charged, and neutral CDs in CE has received the greatest attention.In chapter one of this thesis, the development of chiral separation by CE was reviewed, including theoretical studies, applications and different operating models.In chapter two, three and four,β-CD was modified on the 2,6 hydroxyl positions respectively. Three modifiedβ-CDs were synthesized, 6-O-(2-Hydroxybutyl)-β-CD (6-O-HB-β-CD) and two kinds of cantionicβ-CDs: 6-O-(2-hydroxypropyl)chloridetriethyl ammonium-β-CD (6-O-HPTEA -β- CD) and 2-O-(2-hydroxypropyl) chloridetriethylammonium -β- CD(2-O-HPTEA -β- CD). Thirteen chiral drugs (Ketoconazole, Promethazine, Anisodamine, Chlorp-henamine, Propranolol, Adrenaline, Benzhexol, Fenfluramine, Naproxen, Ofloxacin, Ibuprofen, Warfarin, and Ketoprofen, etc) were separated using the three modifiedβ-CDs as chrial seletors. The effects of the pH of the buffer, the concentrations of the CD derivatives and of the background electrolyte, etc were investigated. We compared the separation effects of the three modifiedβ-CDs with the 2-HP-β-CD andβ-CD under the same separation condition, the result is that the abilities of the threeβ-CD derivatives as chiral selectors are better than of the 2-HP-β-CD andβ-CD.