【作者】 代金玲；

【导师】 姜申德；

【作者基本信息】 天津大学 ， 药物化学， 2007， 硕士

【摘要】 甲磺酸帕珠沙星属于国外开发上市的第四代喹诺酮类药物,在国内属于三类新药。目前与国内市场上销售额最高的三个喹诺酮类药物左旋氧氟沙星、氧氟沙星和环丙沙星相比在抵抗体外细菌的活性和药理毒性方面都具有很大的优势,在国内市场上具有极大的生产和销售潜力。所以帕珠沙星的工业化生产具有很大的经济价值和市场前景。本文参照文献报道的合成路线作了以下几个方面的研究:1.以左旋氧氟沙星中间体((S)-9,10-二氟-3-甲基-2,3-二氢-7-氧代-7-H-吡啶并[1,2,3-de][1,4]苯并噁嗪-6-羧酸乙酯)为起始原料,经亲核取代、选择性脱羧、环丙化、水解、经典Hofmann重排和成盐单元反应合成甲磺酸帕珠沙星,总收率42.46%。其化学结构利用红外光谱、质谱和核磁共振光谱等技术进行确证。2.采用高效层析硅胶板对第一步亲核反应进程进行监控。以甲醇:氯仿:乙酸乙酯:浓氨水=3:7:0.5:0.5混合溶剂作为展开剂,采用光学检测进行定性分析。3.对各步反应机理进行分析,重点研究了亲核取代反应和Hofmann重排反应。课题选用DBDMH- Hg(OAC)2作为Hofmann重排反应试剂,反应条件温和,收率大大提高,适合工业化生产。更多还原

【Abstract】 Pazufloxacin mesilate is the fourth generation of quinolone antibacterial agents that has been come into overseas market recently, and is the third kinds of new pharmaceutical in China. Comparing to the three quinolone antibacterial agents of Levofloxacin, ofloxacin and ciprofloxacin, which have the best sale in home market, pazufloxacin mesilate has the obvious advantages in both of resisting the active bacteric and pharmacological toxicity. So it has huge potential of production and selling in home market,and its industrialization production has the prodigious economy value and market prospect.Referring to the synthesis routes of reference literature, the following three main areas of study have been carried out in the research of this paper.1.Pazufloxacin mesilate was synthesized from (s)-9, 10–difluoro-3-methly-7-oxo-2, 3-dihydro-7H-pyrido [1,2,3-de] [1,4] benzoxazine-6-carboxylate, by nuclephilic substitution, selective decarboxylation, cyclic addition, hydrolysis, Hofmann recomposition and salt formation, the overall yield was 42.46%. Technologies, such as infrared spectrum, mass spectrum and nucleus magnetism spectrum, were applied to identify the chemic structure of this compound.2. A method, which adopting high effect chromatography TLC plate was used to monitor the process of nuclephilic reaction, was put forward. Using mixture of carbinol : chloroform : ethyl acetate : ammonia=3:7:0.5:0.5 as developer, using optical test to make the qualitative analysis.3. Analyzing the reaction mechanism of every process, especially the nuclephilic substitution reaction and Hofmann recomposition reaction were studied. Using DBDMH- Hg (OAC) 2 as reaction reagent of Hofmann recomposition with the mild reaction condition in the research, and the yield has increased greatly, it is be applicable to industrialization production.更多还原