Chemistry of cephalosporin antibiotics. 30. 3-methoxy- and 3-halo-3-cephems.
The exo-methylene group in esters of 7-acylamido- and 7-amino-3-methylenecephams was ozonized to give 3-hydroxy-3-cephems. Conditions are described to effect a selective N-acylation of a 3-hydroxy-3-cephem nucleus ester. Vilsmeier reagents converted 7-acylamido-3-hydroxy compounds to 3-halo-3-cephem derivatives. Diazomethane converted the 3-hydroxy compounds to 3-methoxy-3-cephem derivatives. Removal of the ester-protecting group at the C4-carboxyl afforded a select group of cephalosporins with direct halo and methoxy substitution at C3. A number of these compounds are potent antibiotics.
D002511:Cephalosporins / Q000138:chemical synthesis* / Q000494:pharmacology; D004754:Enterobacter / Q000187:drug effects; D004926:Escherichia coli / Q000187:drug effects; D007711:Klebsiella pneumoniae / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D008826:Microbial Sensitivity Tests; D010403:Penicillin Resistance; D012475:Salmonella / Q000187:drug effects; D012706:Serratia marcescens / Q000187:drug effects; D012760:Shigella / Q000187:drug effects; D013210:Staphylococcus / Q000187:drug effects; D013329:Structure-Activity Relationship
D002511:Cephalosporins