本文關鍵詞： 米格列奈 丁二酸二乙酯 苯甲醛 全合成 工藝優(yōu)化　出處：《青島科技大學》2014年碩士論文　論文類型：學位論文

【摘要】：米格列奈是一種非磺脲類胰島素促分泌的藥物，對于治療糖尿病具備作用時間快、藥效高、給藥靈活和安全性能高等優(yōu)點。本文中針對以往制備米格列奈路線操作復雜、花費高、效率低的問題，對其合成方法進行了改進，，并根據每步實驗反應機理及重要影響因素，對反應條件和操作進行了研究探討，尋找優(yōu)化方法，確定了各步反應的最佳工藝條件，得出一條簡單高效的工藝流程。大致包括以下內容： 文章中首先介紹了米格列奈的結構、性質、藥物作用機制及以往的制備方法；并參照文獻合成路線進行了對比和改進，設計了新的合成路線；另外，還對米格列奈的合成條件及影響產率因素進行了一系列實驗探索，得到本路線最優(yōu)的合成工藝。綜合目前的研究結果和現(xiàn)狀，我們確定了本課題研究內容與方向：米格列奈的合成及其工藝優(yōu)化研究。 本文的實驗部分主要介紹了以丁二酸二乙酯和苯甲醛作為原料，通過Stobbe縮合、烯烴鍵加氫還原、外消旋體拆分、酰胺化、酯鍵水解和成鹽六步反應制得所需的終產物。通過1H-NMR、旋光度、熔點和HPLC分析檢測鑒定，確定最終產物結構，實驗表明，經優(yōu)化后，本路線米格列奈合成的終產率為14.01%，工藝條件溫和，實驗步驟簡單，經濟成本低，易于轉為工業(yè)化生產。
[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.
【學位授予單位】：青島科技大學
【學位級別】：碩士
【學位授予年份】：2014
【分類號】：R914.5

【參考文獻】

相關期刊論文 前10條

1 翁建平;2型糖尿病對社會造成的負擔不容忽視[J];廣東醫(yī)學;2003年10期

2 信建峰;馬吉海;張樹芬;陳韶蕊;李海于;;酰氯制備方法綜述[J];河北化工;2006年11期

3 張德義;加快我國加氫工藝和技術的發(fā)展[J];煉油設計;2002年03期

4 鄭德強;劉文濤;毋立華;孫利民;王長斌;;米格列奈鈣的合成[J];食品與藥品;2007年11期

5 沈洪兵,俞順章,徐耀初;我國糖尿病的發(fā)病變化及其經濟負擔研究[J];上海預防醫(yī)學雜志;1998年09期

6 吳元民,邵寶蓉,顧惠琳,袁杏生,劉紹芳,賈偉平,項坤三;上海市華陽社區(qū)糖尿病、高血壓、血脂紊亂及代謝綜合征基線調查[J];上海醫(yī)學;2001年04期

7 寧光;糖尿病──肆虐全球的流行病[J];世界科學;1999年11期

8 陳慕華;秦曉靜;儲偉;洪景萍;;載體對鈀基選擇加氫催化劑性能的影響[J];石油學報(石油加工);2006年02期

9 南軍,謝海峰,劉晨光;貴金屬選擇性加氫催化劑Pd/Al_2O_3的研究[J];石油煉制與化工;2004年08期

10 唐玲,陳興寶,陳慧云,趙魯勇,胡善聯(lián);中國城市2型糖尿病及其并發(fā)癥的經濟負擔[J];中國衛(wèi)生經濟;2003年12期

本文編號：1463883