Synthesis and activity of potent 3-(isoxazolidin-5-yl)- and 3-(isoxazolidinium-5-yl)cephalosporins.
The syntheses and in vitro antibacterial activities of 3-(isoxazolidin-5-yl)- and 3-(isoxazolidinium-5-yl)cephalosporins are described. 1,3-Dipolar cycloaddition of 3-vinylcephalosporin with nitrone gave diastereomeric isomers of 3-(isoxazolidin-5-yl)cephalosporin. The antibacterial activities of 3'-(S)-isomers were superior to those of 3'-(R)-isomers. The quaternarization of isoxazolidine ring increased the antibacterial activity. Among them, compound 10b with a hydroxyimino group in the C-7 side chain showed potent activities against staphylococci and compound 10f with an N-hydroxypyridone exhibited an excellent antipseudomonal activity.
Huang
S P
SP
Institute of Microbial Chemistry, Tokyo, Japan.
Koyama
Y
Y
Ikeda
D
D
Kondo
S
S
Takeuchi
T
T
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D002511:Cephalosporins / Q000138:chemical synthesis* / Q000494:pharmacology*; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D007536:Isomerism; D007555:Isoxazoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008826:Microbial Sensitivity Tests; D013055:Spectrophotometry, Infrared
D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D007555:Isoxazoles