Synthesis, absolute configuration, and antibacterial activity of 6,7-dihydro-5,8-dimethyl-9-fluoro-1-oxo-1H,5H- benzo[ij]quinolizine-2-carboxylic acid.

The tricyclic quinolone antibacterial agent 6,7-dihydro-5,8-dimethyl-9-fluoro-1-oxo-1H,5H-benzo[ij]quinolizine -2-carboxylic acid has an asymmetric center at position 5 of the molecule. The R and S isomers of the compound have been prepared from the corresponding (R)- and (S)-2,5-dimethyl-6-fluoro-1,2,3,4-tetrahydroquinolines, which were separated via their diastereomeric amides of N-tosyl-(S)-proline. The absolute configuration was established by X-ray analysis of one of the diastereomeric amides. The 5-desmethyl analogue was prepared for antibacterial comparison with the isomers and the racemic mixture. It has now been established that the S isomer is much more active than the R isomer. The 5-desmethyl analogue was found to be more active than the R isomer but not as active as the S isomer or the racemic mixture. The importance of stereochemistry at position 5 in this system has been established.

Differentiation of fluorinated quinolone antibacterials with Neisseria gonorrhoeae isolates.

Clinical isolates of Neisseria gonorrhoeae were tested for growth inhibition by various quinolones. One acrosoxacin-resistant isolate was also resistant to several fluorinated quinolones with 7-heterocyclic substitution, but, inhibitory concentrations were not elevated for quinolones substituted with a methyl group in the corresponding position (nalidixic acid:position 7, S-25930:position 8) or unsubstituted (flumequine:position 8). Isolates resistant to flumequine demonstrated elevated inhibitory concentrations for all quinolones examined.