本文關鍵詞： 糖尿病 藥物中間體 5-氯吡嗪-2-羧酸 葡萄糖激酶激動劑 合成　出處：《重慶醫(yī)科大學》2014年碩士論文　論文類型：學位論文

【摘要】：在近年來研制的新型抗糖尿病藥物中，許多都含有5-氯吡嗪-2-羧酸及其衍生物的結構，例如：葡萄糖激酶激動劑（glucokinase activators，GKAs）、黑色素濃集激素受體拮抗劑（melanin-concentrating hormonereceptor antagonist，MCH）、BACE2抑制劑（Beta-site APP cleavingenzyme2inhibitors）等。為此，以5-氯吡嗪-2-羧酸及其衍生物作為這些新型抗糖尿病藥物的重要中間體，得到了越來越多的關注，對5-氯吡嗪-2-羧酸及其衍生物進行深入研究，將具有一定的理論意義和實用價值。 本著原料價廉易得、操作簡便可行、工藝安全可靠以及易于工業(yè)化生產的原則，結合相關文獻，本文采用逆合成分析法，確定了以2-乙�；秽鳛槠鹗荚虾铣�5-氯吡嗪-2-羧酸的路線。并且在此基礎上合成得到了六個相關衍生物，其主要研究與結果如下： 1.建立了一條以2-乙酰基呋喃為起始原料，經二氧化硒氧化、與甘氨酰胺環(huán)合、三氯氧磷氯化、高錳酸鉀氧化等四步反應合成5-氯吡嗪-2-羧酸的合成路線。該路線具有原料價廉易得、反應條件溫和、操作簡便等特點。 2.在環(huán)合反應中，采用正交實驗法得到最優(yōu)合成條件，使得該步反應收率較文獻（27%）提高了23.1%。 3.在5-氯吡嗪-2-羧酸的合成中，使用鹽酸酸化乙酸乙酯提取法代使用替價格昂貴的強酸性陽離子交換柱，降低了制備成本。 4.在合成得到5-氯吡嗪-2-羧酸的基礎上，合成得到了六個5-氯吡嗪-2-羧酸的衍生物。 綜上所述，，本文以2-乙�；秽珵槠鹗荚�，經二氧化硒氧化、與甘氨酰胺環(huán)合、三氯氧磷氯化、高錳酸鉀氧化等四步反應，建立了一條制備5-氯吡嗪-2-羧酸的合成路線。該路線具有原料價廉易得、操作簡便可行、工藝安全可靠等優(yōu)點。在此基礎上合成得到了六個相關衍生物，為新型抗糖尿病藥物的研究奠定了一定基礎，具有一定的理論意義與實用價值。
[Abstract]:In recent years, many new antidiabetic drugs contain the structure of 5-chloropyrazine-2-carboxylic acid and its derivatives. For example: glucokinase activator GKAs. a glucokinase agonist. Melanin-concentrating hormonereceptor antagonist melanin-concenting hormonereceptor antagonist (MCHs). Beta-site APP cleavingenzyme 2 inhibitors et al. With 5-chloropyrazine-2-carboxylic acid and its derivatives as the important intermediates of these new anti-diabetic drugs, more and more attention has been paid to the study of 5-chloropyrazine-2-carboxylic acid and its derivatives. It will have certain theoretical significance and practical value. Based on the principle of cheap and easy to obtain raw materials, simple and feasible operation, safe and reliable process and easy to industrial production, combined with relevant literature, this paper adopts inverse synthetic analysis method. A route for the synthesis of 5-chloropyrazine-2-carboxylic acid from 2-acetylfuran was established. On this basis, six related derivatives were synthesized. The main research and results are as follows: 1. A starting material of 2-acetylfuran was established, which was oxidized by selenium dioxide, cyclized with glycosaminamide, and chlorinated with phosphorus oxychloride. The synthesis of 5-chloropyrazine-2-carboxylic acid from potassium permanganate oxidation is characterized by its low cost, mild reaction conditions and simple operation. 2. In the cyclization reaction, the optimum synthesis conditions were obtained by orthogonal experiment, and the yield of the step reaction was 23.1g higher than that of the reference (27). 3. In the synthesis of 5-chloropyrazine-2-carboxylic acid, the preparation cost was reduced by the substitution of the expensive strong acid cation exchange column with the extraction of ethyl acetate with acidified hydrochloric acid. 4. Based on the synthesis of 5-chloropyrazine-2-carboxylic acid, six derivatives of 5-chloropyrazine-2-carboxylic acid were synthesized. To sum up, in this paper, 2-acetylfuran was used as the starting material, which was oxidized by selenium dioxide, cyclized with glyamine, chlorinated with phosphorus oxychloride, and oxidized by potassium permanganate. A synthetic route for the preparation of 5-chloropyrazine-2-carboxylic acid was established. This route has the advantages of cheap raw material, simple and feasible operation, safe and reliable process, etc. On this basis, six related derivatives have been synthesized. It lays a foundation for the study of new anti-diabetic drugs and has certain theoretical significance and practical value.
【學位授予單位】：重慶醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2014
【分類號】：R914

【參考文獻】

相關期刊論文 前1條

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