| It is well known that individual enantiomers of chiral drugs show very different pharmacological and toxicological activities. Enantioseparation is one of the main approaches to obtain the optical pure substances, which has important significance in organic chemistry, medicinal chemistry and life science and has become a hot research issue in the world.Micro-column liquid chromatography (micro-HPLC) plays a complementary role in HPLC, because of several key advantages: the ability to work at very low flow rates, which leads to a significantly lower solvent consumption; the possibility to inject very low sample amount; the enhanced detection using concentration-sensitive detectors due to a much lower chromatographic dilution during the separation process (mass sensitivity). These attributes make micro-HPLC develop rapidly.The purpose of the study is to prepare a new micro-column LC system and separate six chiral compounds by the system. The work can be divided into four parts:Firstly, cellulose tris(3,5-dimethylphenylcarbamate) (CDMPC) was synthesized. Elemental analysis and IR spectra indicated that most of the hydroxyl groups of the microcrystalline cellulose had been converted into ester groups. The chiral stationary phase (CSP) was prepared by coating CDMPC on the aminopropyl silica. Coating amount, coating solvents and coating process were investigated.Secondly, micro-LC experiments were carried out using a home-made packed micro-column. One end of the common size column (15cm×4.6mm I.D.) used as a reservoir of the slurry was connected to the pump by a PEEK tube, the other end was connected to the micro-column. The packing materials obtained were self-packed in the micro-column by a slurry method. Dead time and column chromatographic efficiency were determined for all the chiral micro-columns.Thirdly, a kind of home-made micro-column LC system was established successfully. Column, pump, injection and detection systems were optimized simultaneously. The marker used to determine the dead volume was 1,3,5-tri-tert-butylbenzene. The results show that the system has several advantages such as: higher sensitivity, lower consumption of solvents, higher efficiency, better resolution.Lastly, the influence of flow rate, coating amount, 2-propanol content and different alcohols on the enantioselectivity were investigated in detail. Direct optical resolution of five chiral compounds such as Benzoin, Troger's base, Propranolol, Metoprolol, Pindolol were resolved by normal-phase mode using hexane-2-propanol as eluting solvent. Three compounds such as Warfarin, Benzoin and Troger's base were resolved by polar organic-phase mode using methanol as eluting solvent. Baseline separation was almost obtained in all of the chiral compounds mentioned above.
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