抗Ⅱ型糖尿病药物伊格列净的合成研究及托格列净关键中间体的合成研究

发布时间：2018-03-07 21:13

本文选题：SGLT2抑制剂　切入点：伊格列净　出处：《成都学院》2017年硕士论文　论文类型：学位论文

【摘要】：伊格列净和托格列净都是新型抗Ⅱ型糖尿病药物--SGLT2抑制剂,可以阻断肾近曲小管对葡萄糖的重吸收,同时将体内多余的葡萄糖经尿液排出,还能够减少肝糖异生,从而降低血糖水平。本文简述了糖尿病的发病机制、临床上常用的抗Ⅱ型糖尿病药物及其作用机制以及SGLT2抑制剂的研究进展。本文对伊格列净和托格列净的合成路线进行了评述,确定了伊格列净的合成路线和托格列净关键中间体的合成路线并进行了优化。以苯并噻吩和2-氟-5-溴苯甲醛为原料,经过加成,还原得到中间体2-(5-溴-2-氟苄基)苯并噻吩,该中间体与2,3,4,6-四-O-三甲基硅烷基-D-吡喃葡萄糖酸-1,5-内酯经缩合,甲醚化,还原得目标化合物伊格列净,总收率50.12%,纯度98.71%,其结构经质谱、核磁共振氢谱和核磁共振碳谱确证。改进后的合成路线,减少了反应步骤,降低了成本,为工业化生产提供了参考价值。本文还对托格列净的关键中间体的合成进行了探究,以2-溴对苯二甲酸作为起始原料,经过还原,上保护基,与三甲基硅基保护的葡萄糖酸内酯经缩合,脱保护得到关键中间体,为后续托格列净的合成奠定了基础。
[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.
【学位授予单位】：成都学院
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R914

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