摘要
本论文是关于大环抗生素及其衍生物手性固定相合成和其对14种氨基醇类药物对映体的手性分离研究。主要包括大环抗生素手性固定相及其衍生物手性固定相的制备、手性化合物对映体的分离及影响对映体分离各要素的考察与手性识别机理的探讨。
目的：制备大环抗生素手性固定相及其衍生物手性固定相,即替考拉宁手性固定相(TECSP)、1-萘异氰酸酯替考拉宁手性固定相(1-Na-TE CSP)、3,4-二氯苯基异氰酸酯替考拉宁手性固定相(DCP-TE CSP)、万古霉素手性固定相(VAN CSP)、1-萘异氰酸酯万古霉素手性固定相(1-Na-VAN CSP)以及3,4-二氯苯基异氰酸酯万古霉素手性固定相(DCP-VAN CSP),并用于手性药物分析。
方法：基于1,6-己二异氰酸酯具有双官能团、高反应活性的特征,以其为间断臂将替考拉宁或万古霉素键合于γ-氨丙基三乙氧基硅胶表面,制备了2种手性固定相,制备方法简单易行。再将其用1-萘异氰酸酯或3,4-二氯苯基异氰酸酯衍生,得到4种衍生后的手性固定相,并对14种手性药物进行色谱分离。考察了流动相条件、溶质的结构以及固定相的结构对色谱分离的影响。
结果：14种氨基醇类药物对映体在6种手性固定相获得一定程度的分离。
结论：在极性模式下,自制的6种大环抗生素手性固定相对氨基醇类药物对映体有一定的拆分能力。
This dissertation focuses on the enantioseparation using macrocyclic antibiotics chiral stationary phases (CSPs) by high performance liquid chromatography (HPLC), including preparation of macro-cyclic glycopeptides and its1-naphthalene isocyanate and3,4-dichlorobenzene isocyanate derivati-ves, enantioseparation of fourteen amino alcohols chiral compounds, study of several factors concerning chiral separation and discussion of chiral recognition mechanism.
Objective:Preparation of macrocyclic glycopeptides and its1-naphthalene isocyanate and3,4-di chlorobenzene derivatives, such as teicoplanin CSP,1-naphthalene isocyanate teicoplanin CSP,3,4-dichl orobenzene isocyanate teicoplanin CSP,vancomycin CSP,1-naphthalene isocyanate vancomycin CSP and3,4-dichlorobenzene isocyanate vancomycin CSP, and using for analysising of chiral durgs.
Methods:Based on bifunctional and high reactive of1,6-diisocyanatohexane, teicoplanin bonded or vancomycin bonded chiral stationary phase (CSP) was prepared by immobilization of teicoplanin or vancomycin to the surface of3-aminopropyl triethoxy silica using1,6-diisocyanatohexane as spacer. It prepared two kinds of chiral stationary phase. It shows that the preparation method is simple and easy to operate.Using1-naphthalene isocyanate and3,4-dichlorobenzene as derivatives,4kinds of derivative of chiral stationary phase were prepared, and enantioseparation of fourteen amino alcohols chiral compounds. To study the influences of the mobile phase condition, the structure of the solute and the stationary phase structure for chromatographic separation.
Results:It was found that the sixchiral stationary phases had different chrial recognition ability, the fourteen solutes was got good separation on teicoplanin based chiral stationary phase, and also got good separation on vancomycin bascd chiral stationary phase.
Conclusion:In the polar mode, the six self-made macrocyclic glycopeptides chiral stationary phases have certain ability of separation for enantioseparation of amino alcohols.
引文
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