摘要西他沙星（sitafloxacin hydrate）是日本的第一制药三共株式会社（Daiichi Sankyo）于1912年开发的广谱喹诺酮类抗菌药物。其抗菌活性较强，毒副作用也较小。药物结构的C7位上存在一氨基吡咯烷基，可提高药物的抗菌活性。引入此基团需先合成(S)-7-氨基-5-氮杂螺[2.4]庚烷，Youichi Kimura、Nakayama等学者曾报道此中间体的合成。本次设计在已有路线基础上设计实验，希望研究出一种既符合绿色化学原则，同时又适合工业化经济、安全生产的生产路线。27177
通过查阅文献，了解已有的合成方法，总结各方法的优缺点，我们研究并改进了一条合成路线：以乙酰乙酸乙酯为原料，经缩酮、胺酯交换、环化等一系列反应得到所需产物。合成过程中尽量使用低毒试剂以及易回收催化剂，且采用IR、MS、1HNMR等方法对产物进行了表征。
关键词 西他沙星中间体 氨基吡咯烷基 合成路线 工艺优化
毕业论文设计说明书外文摘要
Title The Synthesis of (S)-7-amino-5-aza-spiro[2.4]heptan
Abstract
Sitafloxacin was a broad-spectrum quinolone antibactics, which was developed by Japanese Daiichi Sankyo in 1912. It's antibacterial activity significantly increased than most similar drugs, and it have fewer side effects. There's a amino pyrrole alkyl on sitafloxacin's chemical structure, the existence of this structure has greatly enhanced the antibacterial activity. The introduction of this chemical group demand to synthetize (S)-7-amino-5-aza-spiro[2.4]heptane. Currently Youichi Kimura, Nakayama et al have reported the synthesis of this intermediate. The study mained to design experiments on the basis of existing routes, and developed a more consistent with both the principles of green chemistry, but also for industrialized economy, safety production line.
Through literature, won the currently available (S)-7-amino-5-aza-spiro[2.4]
heptane synthetic method. A reasonable synthesis was designed and studied after summarizing the advantages and disadvantages of each synthetic route. (S)-7-amino-5-aza-spiro[2.4]heptane was prepared by ketalation, amine transesterification reaction and a series of reactions with ethyl acetoacetate as the raw material. Low toxic agent and recoverable catalyst should be used during the process. The products was characterized by IR, MS, 1HNMR.
关键词 intermediate of sitafloxacin amino pyrrolidinyl synthesis process optimization
目 次
1 绪论 1
1.1 概述 1
1.1.1 课题研究背景 1
1.1.2 课题研究的科学意义 1
1.1.3 喹诺酮类抗菌药简介 1
1.1.4 喹诺酮类药物的构效关系 3
1.2 西他沙星简介 4
1.2.1 西他沙星性质简介 4
1.2.2 西他沙星结构简介 4
1.2.3 西他沙星应用前景 5
1.3 西他沙星及其重要中间体的合成 6
1.3.1 西他沙星合成方法简介 6
1.3.2 中间体(1R,2S)-1-氨基-2-氟环丙烷合成方法 7
1.3.3 (S)-7-氨基-5-氮杂螺[2.4]庚烷的合成研究 9
1.3.4 (S)-7-氨基-5-氮杂螺[2.4]庚烷合成路线小结 12
1.4 本文研究内容 12
2 实验部分 14
2.1 实验条件 14
2.1.1 实验仪器 14
2.1.2 分析分离仪器 14
2.2 实验 14
2.2.1 2-甲基-1,3-二氧戊环-2-乙酸乙酯Ⅰ的合成 14 (S)-7-氨基-5-氮杂螺[2.4]庚烷的合成工艺研究:http://www.751com.cn/huaxue/lunwen_21600.html