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摘要：许多药物对映体能呈现完全不同的生理及生物活性，其药效以及药代动力学特征也会有所不同。因此对这些对映体进行分离分析具有非常重要的意义。沙格列汀是糖尿病DPP-IV抑制剂系列最新一代的品种，该药物也是具有手性的。从沙格列汀的化学结构上看，金刚烷片段为沙格列汀的一个关键中间体，它的R, S构型也会对最终的产品产生重要的作用，因此为了得到单一光学纯度的沙格列汀药物在其合成过程中必须严格控制好其关键中间体的R, S构型。本文以沙格列汀的中间体S-(3-羟基-1-金刚烷)-2-(叔丁氧羰基氨基)乙酸（S-Boc-羟基金刚烷氨基酸）及其衍生物S-(1-金刚烷)-乙酸甲酯（S-金刚烷甘氨酸甲酯）为研究对象，利用高效液相色谱法对这两个化合物进行手性拆分，系统地考察了固定相类型、流动相组成及比例、柱温以及流速等影响分离的主要因素并对其进行了优化，建立了利用高效液相色谱法拆分Boc-羟基金刚烷氨基酸及其衍生物金刚烷甘氨酸甲酯对映体的方法。24443
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毕业论文关键词：沙格列汀；高效液相色谱；手性拆分；对映体
HPLC Separation Research on adamantane glycine methyl ester and its derivatives
Abstract: Many chiral drugs can exhibit completely different physiological and biological activities, as well as pharmacodynamics and pharmacokinetic characteristics. Therefore, requiring the analysis and control of the inpidual optically pure enantiomers are of great importance. Saxagliptin is the latest generation varieties of the diabetes DPP-IV inhibitor , the drug also has chirality. From the view of saxagliptin’s chemical structure , adamantane’s fragment is a key intermediation . its R, S configuration of the final product will have an important role in order to obtain the optical purity of the single saxagliptin drug synthesis.In the course, process must be strictly control the key intermediate R, S configuration. In this paper, taking saxagliptin’s intermediation of S-(3-hydroxy-1-adamantyl)-2-(tert-butoxycarbonyl amino) acetic acid (Boc-hydroxy acids) and their derivatives S-(1-adamantane)- methyl acetate (adamantane adamantane glycine methyl ester) as example, by high performance liquid chromatography on two compounds of chiral split and systematically observe the effects of the type of stationary phase, mobile phase composition and proportion, column temperature and flow rate of the main factors affecting the separation.It was optimized and establishes the method of separation of Boc-hydroxy acids and glycine adamantane and Adamantane derivatives of glycine methyl ester enantiomersby high performance liquid chromatography.
Key Words: Saxagliptin; High Performance Liquid Chromatography (HPLC); Chiral
Enantiomer;
目 录
1绪论 1
1.1 课题研究背景及意义 1
1.1.1 课题研究背景 1
1.1.2 课题研究意义 2
1.2 课题研究国内外现状 3
1.3 课题研究期望 4
2 S-BOC-羟基金刚烷氨基酸及其对映体分离的研究 5
2.1 引言 5
2.2 实验部分 5
2.2.1 对映体及色谱溶剂 5
2.2.2 仪器设备 6
2.2.3 实验条件和流动相 6
2.2.4 实验方法 6
2.3 实验结果与讨论 7
2.3.1 色谱条件的选择 7
2.3.2 考察流动相组成对对映体分离条件的影响 7
2.3.3 考察流动相比例对对映体分离的影响 9
2.3.4 考察温度对对映体分离的影响 9
2.3.5 考察流速对对映体分离的影响 11