米格列奈的合成工艺改进

发布时间：2018-01-25 22:36

本文关键词： 米格列奈丁二酸二乙酯苯甲醛全合成工艺优化　出处：《青岛科技大学》2014年硕士论文　论文类型：学位论文

【摘要】：米格列奈是一种非磺脲类胰岛素促分泌的药物，对于治疗糖尿病具备作用时间快、药效高、给药灵活和安全性能高等优点。本文中针对以往制备米格列奈路线操作复杂、花费高、效率低的问题，对其合成方法进行了改进，，并根据每步实验反应机理及重要影响因素，对反应条件和操作进行了研究探讨，寻找优化方法，确定了各步反应的最佳工艺条件，得出一条简单高效的工艺流程。大致包括以下内容：文章中首先介绍了米格列奈的结构、性质、药物作用机制及以往的制备方法；并参照文献合成路线进行了对比和改进，设计了新的合成路线；另外，还对米格列奈的合成条件及影响产率因素进行了一系列实验探索，得到本路线最优的合成工艺。综合目前的研究结果和现状，我们确定了本课题研究内容与方向：米格列奈的合成及其工艺优化研究。本文的实验部分主要介绍了以丁二酸二乙酯和苯甲醛作为原料，通过Stobbe缩合、烯烃键加氢还原、外消旋体拆分、酰胺化、酯键水解和成盐六步反应制得所需的终产物。通过1H-NMR、旋光度、熔点和HPLC分析检测鉴定，确定最终产物结构，实验表明，经优化后，本路线米格列奈合成的终产率为14.01%，工艺条件温和，实验步骤简单，经济成本低，易于转为工业化生产。
[Abstract]:Mieglinide is a non-sulfonylurea insulin secretion drug, which has a rapid effect and high efficacy in the treatment of diabetes. In order to solve the problems of complex operation, high cost and low efficiency, the synthesis method of Mieglinide was improved in this paper. According to the reaction mechanism of each step experiment and the important influencing factors, the reaction conditions and operation were studied and discussed, the optimization method was found, and the optimum process conditions of each step reaction were determined. A simple and efficient process has been developed. It includes the following: In this paper, the structure, properties, drug action mechanism and previous preparation methods of mieglinide were introduced. A new synthetic route was designed by comparing and improving the synthetic route of literature. In addition, a series of experiments were carried out on the synthetic conditions and the factors affecting the yield of Mieglinide, and the optimum synthetic process was obtained, which synthesizes the current research results and the present situation. We have determined the research content and direction of this subject: the synthesis and process optimization of miglinide. In the experimental part of this paper, diethyl succinate and benzaldehyde were used as raw materials, condensation of Stobbe, hydrogenation of olefins, resolution of racemes and amidation of racemes were introduced. The final product was obtained by hydrolysis of ester bond and six steps of salt formation. The structure of the final product was determined by 1H-NMRR, optical rotation, melting point and HPLC analysis. The experimental results showed that the final product was optimized. The final yield of mieglinide is 14.01, the technological conditions are mild, the experimental steps are simple, the economic cost is low, and it is easy to be converted to industrial production.
【学位授予单位】：青岛科技大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R914.5

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