Synthesis and antibacterial activity of novel 7-substituted-6-fluoro-1-fluoromethyl-4-oxo-4H-[1,3]thiazeto[3,2-a] quinoline-3-carboxylic acid derivatives

A series of 7-substituted-6-fluoro-1-fluoromethyl-4-oxo-4H-[1,3]thiazeto [3 ,2-a]quinoline-3-carboxylic acid derivatives (2a-1) was prepared and evalua ted for antibacterial activity These compounds were obtained by deacylation of 4-benzoyloxy-2-(1-chloro-2-fluoroethyl)thio-6,7-difluoroquinoline-3-car boxylate (10) and subsequent intramolecular cyclization followed by substit ution with cyclic amines and then hydrolysis. The intramolecular cyclization reaction of 18, one of the diastereomers (17 , 18) revealed that the cyclization reaction proceeded through an inversion to afford (-)-11a in good chemical and optical yield, The enantiomers of 2 a were prepared from the enantiomers of 11a, which were obtained by the opt ical resolution of the racemate using high-performance liquid chromatograph y (HPLC). Compounds 2a,b showed excellent in vitro and irt vivo antibacterial activit y against both gram-negative and gram-positive bacteria including quinolone and Methicillin-resistant Staphylococcus aureus.