Synthesis and antibacterial activities of 2-oxaisocephems.
A series of 2-oxaisocephems with a thio-substituted methyl group at the 3-position and a 2-aminothiazol-4-yl moiety at the 7-position was synthesized via benzyl 3-acetyloxymethyl-7-azido-8- oxo-1-aza-4-oxabicyclo[4.2.0]oct-2-ene-2-carboxylate (2), derived from benzyl acetoacetate (1). The new 2-oxaisocephems were tested for antibacterial activities. Among them, the derivatives having a [2-(2-aminothiazol-4-yl)-2- (Z)-cyclopentyloxyimino]acetamido group at the 7-position characteristically showed potent activities against gram-positive bacteria including methicillin-resistant Staphylococcus aureus (MRSA) and Enterococcus faecalis as compared with cefuzonam and cefmenoxime, which are third-generation cephalosporins.
Tsubouchi
H
H
Microbiological Research Institute, Otsuka Pharmaceutical Co., Ltd., Tokushima, Japan.
Tsuji
K
K
Yasumura
K
K
Ishikawa
H
H
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002511:Cephalosporins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D009682:Magnetic Resonance Spectroscopy; D008745:Methylation; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D002511:Cephalosporins