摘 要

莫西沙星是新一代的抗菌药--第四代喹诺酮类抗菌药。作为新一代的抗菌药，其具有更新颖的结构特征和更良好的性能，如在药代动力学方面有较为明显的改善、抗菌谱也更加广泛，与此同时，它对人体的毒副作用在一定程度上也有所降低。因此，莫西沙星作为新一代的抗菌药在临床用药上取得了巨大的成功，对其进行更加深入的探索，开发更为广阔的市场成为了我们如今的研究方向。本文重点研究了莫西沙星这个药物的关键中间体，找到了一条能满足工厂生产要求的工艺路线。该条路线具有初始物料常见、容易上手操作、产品产量多和价钱低等优点。本文选择的路线的反应具体工艺情况如下：

关键词：莫西沙星，关键中间体，拆分，(S, S)-2, 8-二氮杂双环[4.3.0]壬烷

ABSTRACT

Moxifloxacin is a new broad-spectrum fluoroquinolone drugs for treatment of patients with upper respiratory tract infection (such as community acquired pneumonia, acute sinusitis, chronic bronchitis acute attack and skin and soft tissue infections) of adult, with antibacterial activity, broad antibacterial spectrum, not easy to produce resistance, effective on common drug resistant bacteria, long half-life, less adverse reaction and many advantages. On the market demand for this kind of medicine is increasing day by day, how to better and faster synthesis has become the focus of our research. Moxifloxacin in the production process, production cost mainly from on the side chain (s, s) and esculetin on trans diaza dicyclic por nonane synthesis, due to the side chain is a chiral structure, original Industrialization Route mostly in the late production to split, wait until the product of SS configuration, nearly half of RR configuration because conversion cannot be discarded. Therefore, how to improve the yield of moxifloxacin side chain, get a suitable for industrialized production process, reduce production cost is the focus of this paper. This paper chooses the route of reaction specific process conditions as follows:

(1) N-benzyl-2, 3-dicarboxylicimide was synthesized by 2, 3- Pyridinedicarboxylic acid and benzylamine with methylbenzene as a solvent.

(2) Using Pd/C as a catalyst, 8-benzyl-7, 9-dioxo-2, 8-diazabicyclo

[4.3.0]nonane was prepared through hydrogenation reduction of

N-benzyl-2,3- dicarboxylicimide.

(3)Use D-(–)-tartaric acid as resolution agent, (1S, 6R)-8-benzyl-7,

9-dioxo-2, 8-diazabicyclo[4.3.0]nonane was prepared from 8-benzyl-7, 9-dioxo-2,8 –diazabicyclo[4.3.0]nonane.

(4) Using Na BH4 and BF3•Et2O as a reductive agent, (S, S)- 8-benzyl-2, 8-diazabicyclo[4.3.0]nonane was prepared from (1S, 6R)- 8-benzyl-7, 9-dioxo-2, 8-diazabicyclo[4.3.0]nonane .

(5) (S, S)-2, 8-diazabicyclo[4.3.0]nonane was prepared through hydrogenation reduction of (S, S)-8-benzyl-2, 8-diazabicyclo[4.3.0] nonane .

KEY WORDS: moxifloxacin, synthesis, resolution, (S, S)-2, 8-diazabicyclo[4.3.0]nonan

目录

摘要 I

ABSTRACT II

第一章：绪论 1

1.1莫西沙星简介 1

1.2莫西沙星关键中间体研究现状 1

1.4选题目的及拟采用的合成路线 7

第二章：实验过程 9

2.1N-苄基-吡啶-2, 3-二甲酰亚胺的合成 10

2.1.2反应机理 10

2.1.3 实验所用试剂见下表 11

2.1.4 实验步骤及现象 12

2.1.5 结果与讨论 12

2.2 8-苄基-7, 9-二氧代-2, 8-二氮杂双环[4.3.0]壬烷的合成 16

2.2.1 反应方程式 16

2.2.2反应机理 16

2.2.3 实验所用试剂见下表 16

2.2.4 实验步骤及现象 16

2.2.5 结果与讨论 17

2.3 (1S, 6R)-8-苄基-7, 9-二氧代-2, 8-二氮杂双环[4.3.0]壬烷的合成 18

2.3.1反应方程式 18

2.3.2反应机理 18

2.3.3 实验所用试剂见下表 18

2.3.4 实验步骤及现象 19

2.3.5 结果与讨论 19

2.4 (S, S)-8-苄基-2, 8-二氮杂双环[4.3.0]壬烷的合成 20

2.4.1 反应方程式 20

2.4.2 反应机理 21

2.4.3 实验所用试剂见下表 21

2.3.4 实验步骤及现象 22

2.4.5 结果与讨论 22

2.5 (S, S)-2, 8-二氮杂双环[4.3.0]壬烷的合成 23

2.5.1 反应方程式 23

2.5.2 反应机理 24

2.5.3 实验所用试剂见下表 24

2.5.4 实验步骤及现象 24

2.5.5 结果与讨论 24

第三章：结论与展望 27

3.1主要结论 27

3.2实验中出现的问题 29

参考文献 30

附录： 32

致 谢 33

第一章：绪论

莫西沙星是新一代的抗菌药--第四代喹诺酮类抗菌药。作为新一代的抗菌药，其具有更新颖的结构特征和更良好的性能，如在药代动力学方面有较为明显的改善、抗菌谱也更加广泛，与此同时，它对人体的毒副作用在一定程度上也有所降低。因此，莫西沙星作为新一代的抗菌药在临床用药上取得了巨大的成功，对其进行更加深入的探索，开发更为广阔的市场成为了我们如今的研究方向。本文重点研究了莫西沙星这个药物的关键中间体，找到了一条能满足工厂生产要求的工艺路线。该条路线具有初始物料常见、容易上手操作、产品产量多和价钱低等优点。

1.1莫西沙星简介

莫西沙星(Moxifloxacin)