Study On The Synthesis Of Prulifloxacin

Prulifloxacin (NM441or AF3012) was a novel fourth generation fluoroquinolone antibacterial developed by Nippon Shinyaku and Meiji Seika (Japan) and not yet came into market in China. It is the lipophilic prodrug of NM394(AF3013), the active metabolite was abscised4-[(5-methyl-2-oxo-1,3-dioxol-4-yl) methyl] moiety on C7of prulifloxacin by dioxygen enzyme in portal vein and liver after which was absorbed in the small intestine. Prulifloxacin has a board antibacterial spectrum, including Gram-negative bacteria, Gram-positive bacteria, Anaerobe, Legionella, Chlamydozoan and Mycoplasma. It is generally more active than other fluoroquinolones and antibiotics against Gram-negative bacteria, especially to aeruginosus Bacillus. Studies published abroad showed the drug has little accumulation in vivo after multiple administrations. Unlike the other fluoroquinolones with various unexpected toxicity problems (phototoxicity, cardiotoxicity, hepatotoxicity), the rate of adverse effect of it is rare.The key intermediate Ethyl6,7-difluoro-1-methyl-4-oxo-4H-[1,3]thiazolo[3,2-a]quinoline-3-carboxylate (9) was obtained by using3,4-difluoroaniline as material. After hydrolysis in the presence of potassium hydroxide, the intermediate9can be reacted with4-Bromomethyl-5-methyl-1,3-dioxol-2-one to give prulifloxacin.All products were characterized by modern analytical methods including UV, IR and1HNMR.