(S)-2-取代吡咯烷类化合物的合成研究
毕业论文关键词： (S)-2-取代吡咯烷；合成；增效基团
Synthesis of (S)-2-substituted pyrrolidine
Abstract：In view of the (S)-2-substituted pyrrolidine is synergistic group of drugs, the group can effectively regulate the physicochemical properties of drugs, improve the pharmacokinetics properties and the biological activity of drugs by forming multiple hydrogen bonds or ionic bonds. While the pyrrolidine compounds show different biological activities with different substituents, position or connection modes, they display perse chemical structures and a wide range of pharmacological activities. Particularly the introduction of the 2 substituent pyrrolidine fragments in the target compound, especially when the aromatic methylformamide aromatic ethers is connected to 2 position of pyrrolidine ring. Therefore，in this paper, we synthesized 3 aromatic acid fragments . Also use EDCI as coupling agent and HOBT as catalyst via giving BOC, carboxyl reduction, condensation and removal of BOC group four reaction steps to synthesis two (S)-2-substituted pyrrolidine for the development of new drugs. The 3 aromatic acid fragments and 2 target compounds were confirmed by mass spectrum or NMR structure .
Key words：(S)-2-substituted pyrrolidine ; synthesis ; efficient group
目录
1 绪论 1
1.1 研究背景 1
1.1.1 概述 1
1.1.2 DPP-4及其抑制剂简介 2
1.2 研究现状 2
1.2.1 DPP-4酶抑制剂研究进展 2
1.2.2 已上市DPP-4抑制剂类抗糖尿病药物介绍 3
1.2.3 在研DPP-4抑制剂类抗糖尿病药物介绍 4
1.3 本文研究方向，重点及意义 6
1.4 酰胺缩合方法的选定 7
1.4.1 混合酸酐法 7
1.4.2 鎓盐类缩合剂法 8
1.4.3 有机磷类缩合剂法 9
1.4.4 碳二亚胺类缩合剂法 9
1.4.5 本课题所用合成方法 10
2 实验部分 12
2.1 仪器与试剂 12
2.1.1 实验仪器 12
2.1.2 实验试剂 13
2.2 芳香甲酸片段的合成 14
2.2.1 化合物F-S-A的合成步骤 14
2.2.2 化合物3-S-A的合成步骤 14
2.2.3 化合物C-S-A的合成步骤 15
2.3 (S)-2-取代吡咯烷的合成 15
2.3.1 L-NiPD-NH的合成步骤 15
2.3.2 L-MSP-NH的合成步骤 16
3 结果与讨论 18
3.1 芳香甲酸片段的数据记录与处理 18
3.1.1 F-S-A 18
3.1.2 3-S-A 18
3.1.3 C-S-A 19