旋光性聚合物HPLC-CSP的制备及手性拆分能力的研究

手性是自然界的一种普遍现象，生命现象离不开手性。手性物质在有机化学、药物化学、生物化学以及功能材料等领域显示出诱人的应用前景。外消旋体的拆分是手性研究的重要基础工作。高效液相色谱手性固定相法（HPLC-CSP）在对映体化合物的分离分析和制备方面表现出独特的优势。本论文以旋光性联萘类聚合物和纤维素类衍生物涂敷的手性固定相进行分析级和半制备级色谱拆分，研究和探讨了它们对外消旋化合物的手性识别能力。1. 纤维素类聚合物的合成 将微晶纤维素与相应的酰氯或异氰酸酯反应获得四种纤维系类衍生物，纤维素三苯甲酸酯（CTB）、纤维素三苯基氨基甲酸酯（CTPC）、纤维素三（3,5-二甲基苯基氨基甲酸酯）（CDMPC）、纤维素三联萘甲酸酯（CTBPT）。红外、核磁、元素分析证明原料纤维素已酯化完全。2. 旋光性聚合物手性固定相及HPLC手性柱的制备采用聚合物涂敷硅胶方法制备了四种纤维素类、三种联萘聚酰胺手性固定相和二种半制备级纤维素手性固定相，匀浆法装柱。研究了不同的涂敷液对色谱柱效的影响。3. 旋光性联萘聚酰胺手性柱拆分能力的探讨 在三种由（S）-联萘聚酰胺涂敷的色谱柱上，以多种流动相体系对多种外消旋化合物进行手性折分试验。4. 纤维素类手性分析柱拆分能力的研究 对手性柱进行塔板数和稳定性测试及拆分能力研究。对一些外消旋化合物实现了手性拆分。由实验结果可以看出，以CDMPC涂敷的手性柱对多种外消旋化合（包括药物）具有手性拆分能力，具分离度较高。5. 半制备级拆分 对三种外消旋药物在纤维素半制备色谱柱上进行了半制备级拆分。我们在分析型色谱柱进行了流动相条件的选择，将优化后的分析条件直接放大到半制备色谱中，不仅节省了模索条件的时间，而且可以节省大量的流动相，预计一天内所能达到的对外消旋体最大拆分量可达克级以上。6. 进行了HPLC-UV-旋光仪的联用检测研究，实现了在线流动过程中旋光曲线的绘制。The existing of enantiomers is ubiquity in nature. Chiral substances are extremely important in the area of organic chemistry, pharmaceutical chemistry and biochemistry, et al.. Resolution of racemates is an important fundamental work. Chromatographic enantioseparations, particularly resolution by high-performance liquid chromatography with chiral stationary phase (HPLC-CSP) has been proved to predomaince in the analytical and preparative separations of enantiomers. In this thesis, CSPs were preparated by silical gel coated with (S)-binaphthyl polymers and cellulose derivatives, and used in chiral resolution. Their chiral recognition abilities were also studied. 1. The synthesis of cellulose derivatives Four cellulose derivatives, such as tribenzoate, triphenylcarbamate, tris(3,5-dimethylphenylcarbamate), tris(binaph-benzoate) of cellulose, were prepared by the reaction of micrycrystalline cellulose with corresponding chlorides or substituted phenyl isocyanates in dry pyridine. IR, NMR and Elemental Analysis indicate that almost all hydroxy groups of cellulose have been converted. 2. The preparation of CSPs and HPLC chiral columns CSPs were preparated by the silica gel coated with about 16-20% optically active polymers, include four cellulose derivatives, three (S)-binaphthyl polymers, used for analytical and semi-preparative separations. The HPLC chiral columns were packed by the slurry method. The condition of the preparation of CSPs, such as the coating solvents (THF and CHCl_3), have effect on the chiral recognition of CSPs. 3. The discussion of chiral resolution abilities of (S)-binaphthyl columns Some racemates were tried to be resoluted by some moblie phases on three (S)-binaphthyl columns. 4. The research of HPLC chiral analytical cellulose columns The column plate numbers, stabilities and resolution abilities of chiral cellulose columns have been investigated. Some racemates were resoluted by these chiral columns and their chromatogram and resolutional data were obtained. CDMPC columns exhibited higher chiral recognition for various racemates, include chiral durgs. 5. Semi-perparative chromatographic resolution by cellulose columns Three chiral drugs, such as propranolol, alprenolol, warfarin, were resoluted by two semi-perparative cellulose columns. 6. The on line curves of polarimeter were obtained by HPLC-UV-Polarimeter