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

• Published in: Journal of medicinal chemistry 1987-05, Vol.30 (5), p.839-843
• Main Authors: Gerster, John F, Rohlfing, Steve R, Pecore, Sharon E, Winandy, Richard M, Stern, Richard M, Landmesser, June E, Olsen, Roger A, Gleason, William B
• Format: Article
• Language: English
• Subjects: Bacteria - drug effects; Chemical Phenomena; Chemistry; Condensed matter: structure, mechanical and thermal properties; Exact sciences and technology; Heterocyclic compounds; Heterocyclic compounds with only one n hetero atom and condensed derivatives; Magnetic Resonance Spectroscopy; Molecular Conformation; Organic chemistry; Organic compounds; Physics; Preparations and properties; Quinolizines - chemical synthesis; Quinolizines - pharmacology; Stereoisomerism; Structure of solids and liquids; crystallography; Structure of specific crystalline solids; Structure-Activity Relationship; X-Ray Diffraction
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm00388a016

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.