本文選題：SGLT2抑制劑　切入點(diǎn)：伊格列凈　出處：《成都學(xué)院》2017年碩士論文　論文類型：學(xué)位論文

【摘要】：伊格列凈和托格列凈都是新型抗Ⅱ型糖尿病藥物--SGLT2抑制劑,可以阻斷腎近曲小管對(duì)葡萄糖的重吸收,同時(shí)將體內(nèi)多余的葡萄糖經(jīng)尿液排出,還能夠減少肝糖異生,從而降低血糖水平。本文簡(jiǎn)述了糖尿病的發(fā)病機(jī)制、臨床上常用的抗Ⅱ型糖尿病藥物及其作用機(jī)制以及SGLT2抑制劑的研究進(jìn)展。本文對(duì)伊格列凈和托格列凈的合成路線進(jìn)行了評(píng)述,確定了伊格列凈的合成路線和托格列凈關(guān)鍵中間體的合成路線并進(jìn)行了優(yōu)化。以苯并噻吩和2-氟-5-溴苯甲醛為原料,經(jīng)過(guò)加成,還原得到中間體2-(5-溴-2-氟芐基)苯并噻吩,該中間體與2,3,4,6-四-O-三甲基硅烷基-D-吡喃葡萄糖酸-1,5-內(nèi)酯經(jīng)縮合,甲醚化,還原得目標(biāo)化合物伊格列凈,總收率50.12%,純度98.71%,其結(jié)構(gòu)經(jīng)質(zhì)譜、核磁共振氫譜和核磁共振碳譜確證。改進(jìn)后的合成路線,減少了反應(yīng)步驟,降低了成本,為工業(yè)化生產(chǎn)提供了參考價(jià)值。本文還對(duì)托格列凈的關(guān)鍵中間體的合成進(jìn)行了探究,以2-溴對(duì)苯二甲酸作為起始原料,經(jīng)過(guò)還原,上保護(hù)基,與三甲基硅基保護(hù)的葡萄糖酸內(nèi)酯經(jīng)縮合,脫保護(hù)得到關(guān)鍵中間體,為后續(xù)托格列凈的合成奠定了基礎(chǔ)。
[Abstract]:Both Iglidine and Toglitaxel are new type 2 diabetes drugs, SGLT2 inhibitors that block the reabsorption of glucose by the proximal tubule of the kidney, while excreting excess glucose from the body through the urine and reducing liver glucose allogenesis. In order to reduce blood sugar level, this article briefly describes the pathogenesis of diabetes mellitus, Advances in the study of antidiabetic drugs and their mechanisms and SGLT2 inhibitors are reviewed in this paper. The synthetic routes of Eglicine and Toglitaxel are reviewed in this paper. The synthetic route of Iglicine and the synthesis route of the key intermediate of toglennet were determined and optimized. Benzothiophene and 2-fluoro-5-bromobenzaldehyde were used as raw materials and the intermediate 2-bromo-2-fluorobenzyl) benzothiophene was reduced to benzothiophene. The intermediate was synthesized by condensation, methylation and reduction of the target compound Iglidine with a total yield of 50.12 and a purity of 98.71. Its structure was characterized by mass spectrometry. The improved synthesis route reduces the reaction steps, reduces the cost and provides a reference value for industrial production. The synthesis of the key intermediate of Toglitaxel is also studied in this paper. The key intermediate was obtained by condensation of 2-bromo-terephthalic acid with trimethylsilyl-protected gluconolactone after reduction and protection, which laid a foundation for the subsequent synthesis of toglyphane.
【學(xué)位授予單位】：成都學(xué)院
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R914

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