摘要咪达普利是由日本田边制药研发的一种新型抗高血压药物，属于血管紧张素转换酶抑制剂（ACEI），因其降压效率高, 选择性好，降压疗效稳定，临床上被广泛用于治疗高血压和一些心血管疾病，具有广阔应用前景。因此对咪达普利合成方法的研究有重要的意义。62956

本文介绍了几种咪达普利已有的合成方法，并比较了几种合成方法的优缺点，总结出一条优化的合成路线，选择(2R)-2-对甲苯磺酰氧基丙酰氯和(4S)-1-甲基-2-氧代咪唑啉-4-羧酸叔丁酯为中间体。并以N-苄氧羰基-L-天冬酰胺为原料，经Hofmann重排、酯化、N-甲基化、催化氢化得到(4S)-1-甲基-2-氧代咪唑啉-4-羧酸叔丁酯。通过单因素实验筛选出了最佳反应条件，并用红外、质谱、核磁分析手段对每一步产物进行表征，确定了合成方法的可行性。

毕业论文关键词 咪达普利，合成方法，优化，中间体

Title      Study on the synthesis process of imidapril     

Abstract Imidapril is a new anti-hypertensive drug developed by Japanese Tanabe Seiyaku Co Ltd as a kind of angiotensin converting enzyme inhibitors (ACEI). Noted for its high efficiency, good selectivity and stability of of anti-hypertension, Imidapril has been widely used in clinic to treat high blood pressure and cardiovascular diseases with a broad application prospect. Therefore, study on the synthesis of Imidapril is of great importance.

Five pre-exsiting synthetic methods of imidapril were introduced and compared in this paper and a novel synthetic route was developed based on the summary of pre-exsiting synthetic methods with the  (2R)-2-(p-toluenesulfonyloxy) propionyl chloride and tert-Butyl (4S)-1- methyl-2-oxoimidazolidine-4-carboxylate as the intermidates. tert-Butyl (4S)-1- methyl-2-oxoimidazolidine-4-carboxylate was prepared via Hofmann rearrangement, esterification, N-methylation and catalytic hydrogenation of N-benzyloxycarbonyl-L- asparagine as the startnig material.Then the optimum reaction conditions were screened out by single factor experiments. Products of each step were characterized and certified by infrared spectroscopy(IR), 1H nuclear magnetic resonance(HNMR), mass(MS).

Keywords   Imidapril   Synthesis   Optimization   Intermediate

毕业设计说明书（论文）外文摘要 

1  绪论 1

1.1  选题背景与意义 1

1.2  咪达普利简介 2

1.2.1  基本信息 2

1.2.2  咪达普利的药理学特性 2

1.2.3  咪达普利的临床疗效和临床治疗意义 3

1.3  咪达普利合成路线选择 4

1.3.1  已有的咪达普利合成路线 4

1.3.2  课题选定的合成路线 9

1.4  课题研究内容 10

2  实验部分 11

2.1  实验仪器与试剂 11

2.1.1  实验试剂 11

2.1.2  实验仪器 12

2.2  (4S)-3-苯甲氧羰基-2-氧代咪唑啉-4-羧酸的合成 12

2.2.1  反应方程式 12

2.2.2  实验操作 13

2.2.3  产物谱图分析鉴定 13

2.3  (4S)-3-苯甲氧羰基-2-氧代咪唑啉-4-羧酸叔丁酯的合成