Synthesis of 9-oxime-11,12-carbamate ketolides through a novel N-deamination reaction of 11,12-hydrazonocarbamate ketolide.
A series of 9-oxime-11,12-carbamate ketolides was synthesized for the first time through a key 11,12-hydrazonocarbamate intermediate that was first oximated and further deaminated to give the corresponding carbamate. The N-N bond cleavage was achieved through an original new reaction using glycoaldehyde dimer as deaminating reagent. The new compounds synthesized were shown to display improved antibacterial activities against Streptococcus pneumoniae and S. pyogenes resistant to erythromycin.
Denis
Alexis
A
Medicinal Chemistry Department, Aventis Pharma 102 route de Noisy, Cedex F-93235, Romainville, France. alexis.denis@pfizer.com
Pejac
Jean-Marie
JM
Bretin
François
F
Bonnefoy
Alain
A
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002219:Carbamates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D018942:Macrolides / Q000138:chemical synthesis / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D008968:Molecular Conformation; D010091:Oximes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013296:Streptococcus pneumoniae / Q000187:drug effects; D013297:Streptococcus pyogenes / Q000187:drug effects
D000900:Anti-Bacterial Agents; D002219:Carbamates; D018942:Macrolides; D010091:Oximes