【作者】 李明；

【导师】 张勇； 郑利刚；

【作者基本信息】 河北科技大学 ， 制药工程（专业学位）， 2017， 硕士

【摘要】 随着体力活动的减少和不健康的饮食,糖尿病已成为一种严重危害人类健康的疾病。防治糖尿病已成为重要的、紧迫的医疗保健问题之一,因此糖尿病药物的研发也成为时下医药行业的焦点。治疗糖尿病药物主要分为五种:胰岛素和胰岛素类似物、胰岛素分泌促进剂、胰岛素增敏剂、α-葡萄糖苷酶抑制剂和二肽基肽酶-Ⅳ抑制剂(DPP-Ⅳ抑制剂)。DPP-Ⅳ抑制剂作为一种新型降糖药,比当前其他降糖药具有一定优势,替格列汀则属于DPP-Ⅳ抑制剂。本文通过对比已报道文献中替格列汀合成路线的优劣,确定了采用以反式-4-羟基-L-脯氨酸为起始原料的合成路线。即以反式-4-羟基-L-脯氨酸为起始原料,经过甲基化,氨基保护,羟基的活化,与1-(3-甲基-1-苯基-1H-吡唑-5-基)哌嗪缩合,然后水解再与噻唑烷缩合,最后脱保护得到替格列汀。目标化合物的结构经核磁共振(1H-NMR和13C-NMR)、红外光谱等确证,总收率为55.36%。更多还原

【Abstract】 With the reduction of physical activity and unhealthy diet,diabetes has become a common and frequently-occurring disease,which is a serious harm to human health.Prevention and treatment of diabetes has become one of the important and urgent medical care problems,so the development of diabetes drugs has become the focus of the pharmaceutical industry.The drugs are mainly divided into five kinds: Insulin and Insulin Analoges,Promoter to Insulin Secretion,Insulin Enhancers,α-Glucosidase Inhibitors and Dipeptidyl Peptidase-Ⅳ Inhibitors.DPP-Ⅳinhibitor,as a new hypoglycemic drug,has some advantages over other hypoglycemic agents,Teneligliptin is an inhibitors.In this paper,by comparing the advantages and disadvantages of Teneligliptin synthetic routes in the reported literature,the synthetic route with(2S,4R)-4-hydroxypyrrolidine-2-carboxylic acid as the starting material was determined.Using(2S,4R)-4-hydroxypyrrolidine-2-carboxylic acid as starting material,through methylation,amino protection,the activation of hydroxyl,and 1-(3-Methyl-1-phenyl-5-pyrazolyl)piperazine condensation,then hydrolysis and thiazole condensation,finally take off Teneligliptin.The structure of the target compounds were confirmed by nuclear magnetic resonance(1H-NMR and 13C-NMR),infrared spectroscopy.the total yield was 55.36%.更多还原