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摘要：Miglitol是德国拜耳制药公司20世纪80年代初研究开发的一种新型降糖药，是一种新的小肠α-葡萄糖苷酶抑制剂。米格列醇的结构与葡萄糖相似，能够可逆地竞争性抑制假单糖α―葡萄糖苷酶，对小肠绒毛刷缘的α－糖苷酶有抑制作用，是蔗糖酶的高效抑制剂，且不抑制α－淀粉酶的活性。由于作用机制为可逆竞争性抑制，因而该化合物并不完全抑制葡萄糖的吸收，而是延缓了葡萄糖的吸收过程，使消化道各区域对葡萄糖的吸收更平均，从而平缓了餐后碳水化合物消化吸收所产生的尖锐血糖峰值。本课题是以2,3,4,6-四苄基葡萄糖为原料，用硼氢化钠作为还原剂还原半缩醛，之后经新戊酰化、Mitsunobu反应、甲磺酰氯脱酰等一系列步骤，通过立体构型的两次翻转后制得米格列醇的新化学合成路线的研究。通过一系列的实验研究最终确定了这一条较高收率低成本、操作简便，绿色环保且较为安全的工艺路线。结果表明，该路线相对较短而且产率较高，约有50%的总收率，而且改变初始原料糖或者改变亲核取代反应的胺，可以得到很多不同的糖胺，供化学生物学筛选不同的生理活性的分子。48221
毕业论文关键词：米格列醇；Mitsunobu反应；双反转策略
Study on synthesis of Miglitol new route
Abstract: Miglitol is a new type of hypoglycemic agent developed by German pharmaceutical company Bayer in early 1980s. It is a new type of small intestinal α-Glucosidase Inhibitors. Miglitol structure is similar to glucose, it can be reversible competitive inhibition of the α-Glucosidase inhibitors and the α-Glucosidase of small intestinal brush border. It is an efficient inhibitor of invertase, and does not inhibit the activity of α-amylase. Due to the mechanism of reversible competitive inhibition, the compound does not completely inhibit the absorption of glucose, but delay the absorption of glucose. It makes the absorption of glucose in different regions of the digestive tract more evenly. Thus, the peak value of the acute blood sugar produced by the digestion and absorption of carbohydrates after meal was gentle. This topic is based on the 2, 3, 4, 6- four benzyl glucose as raw material, using sodium borohydride as reductant for reducing hemiacetal. After the neopentyl acylation, Mitsunobu reaction and methylsulfonyl chloride deacylation and a series of steps, through two flip of the stereo configuration preparing Miglitol. Through a series of experimental studies, this article has determined the high yield, low cost, easy to operate, green and safe process route. The results show that the route is relatively short and the yield is relatively high, and the total yield is about 50%. And changing the initial material sugar or the pro nuclear substitution of amines, can get a lot of different amines for chemical biology to screen different physiological activities of the molecule.
Keywords：Miglitol；Mitsunobu reaction；Double inversion strategy
目 录
1 绪论 1
1.1 课题研究背景及意义 1
1.2 Miglitol的相关简介 3
1.2.1 Miglitol的相关化学信息 3
1.2.2 Miglitol的应用价值 3
1.2.3 Miglitol的药理作用及药动学代谢 4
1.3 立体结构构型翻转的机理及意义 4
1.4 Mitsunobu反应简介 5
1.5 SN2取代反应简介 6
1.6 野尻霉素及其衍生物的合成研究现状