Improved Synthesis Route And Mechanism Research Of Pazufloxacin Mesylate

Quinolones medicine is one kind of antibacterials by manual synthesismethod, which has the excellent antibacterial character and the wide clinicaluasge with the good benefits, such as the lower adcerse effect, many ways ofresorbing, the good propety of medicine kinetics and et. al. In 1962 the firstages were develpoed and came into the market, and after 40 years' developingthere are four ages products, which always catch the attention from theinvestigators and users. In the future, it will sustain the developing rate of5-8% still. In 2009, the market of the quinolones medicines will take up 34%,which will exceed the quotientof the Cephalosporins medicines and theBeta-Lactam Antibiotics medicines, and become to the first anti-infectionpharmacy.IN this paper, the structure-activity relationship,evolution gradation,production and market demand,the future of research and development weresummarized. The technological progress, new agents and characters forquinolone antibacterial agents were also discourse.Pazufloxacin Mesylate, Pasil for the trade name, has came into themerket in Japan in 2002 firstly, which has a wide clinical uasage, the higherblood concentration by intravenously, higher effective speed, lower toxicity of central nervous system. The benefit of the pazufloxatin mesylas is also betterthan the levofloxacin, norfloxaxin, ciprofloxacin, and ofloxacin for the vivoactivity of the staphylococcus aureus, especially for the drug resistance. It willbe the main product after several products developed. The paper alsodescribed the biological activities of Pazufloxacin Mesylate and analysis thedevelop progress in detail.According to the reports, there are two synthesis pathes about thepazufloxacin mesylate. The first path: It was synthesized cyancyclopropyl atfirst,then framework.It started from 2,3,4,5-tetrafluoro-benzoic acid. Thesecond path: It was synthesized from (s)-9,10-difluoro-3-methyl-7-oxo-2,3-dihydro-7H-pyrido [1,2,3-de] [1,4] benzoxazine-6-carboxylate.In the path,thefirst intermidiate was synthesized by nucleophilic substitution,hydrolysis anddecarboxylation.It needed two kinds of reactions. Based on the analysis forreports, the synthesis path was improved in this paper. The compound wassynthesized from (s)-9,10- difluoro- 3-methyl-7-oxo-2,3-dihydro-7H-pyrido-[1,2,3-de][1,4]benzoxazine-6-carboxylic acid by nucleophilic substitution,cyclic addition, hydrolysis, Hofmann degradation and salt formation with themethane sulfonic acid. This technics has higher rate, simple operating steps,the shorter period of production, which indicates this synthsis is suitabole forthe industial manufacture.The paper also analysised and discussed the reaction mechanism ofsynthesis course in detail. As well as, it considered the factors of technics conditions, such as reaction time, temperaturre, and different catalysts.Fouthermore, the structure of the intermediate were confirmed by Afterthese steps, we get the preferred tecnics path.