Synthesis and beta-lactamase inhibitory properties of 2 beta-(chloromethyl)-2 alpha-methylpenam-3 alpha-carboxylic acid 1,1-dioxide.
Potassium 2 beta-(chloromethyl)-2 alpha-methylpenam-3 alpha-carboxylate 1,1-dioxide (BL-P2013) and its pivaloyloxymethyl ester were prepared by the conversion of 6-aminopenicillanic acid to p-nitrobenzyl 6 alpha-bromo-2,2-dimethylpenam-3 alpha-carboxylate 1-oxide, which was rearranged with benzoyl chloride and quinoline to p-nitrobenzyl 6 alpha-bromo-2 beta-(chloromethyl)-2 alpha-methylpenam-3 alpha-carboxylate in 65% yield. Oxidation and catalytic hydrogenation afforded BL-P2013, which was found to be a potent inhibitor of various bacterial beta-lactamases and has been found to protect amoxicillin from beta-lactamases in both in vitro and in vivo systems.
D000658:Amoxicillin / Q000494:pharmacology; D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D019818:Clavulanic Acid; D004927:Escherichia coli Infections / Q000188:drug therapy; D051379:Mice; D008813:Mice, Inbred ICR; D010397:Penicillanic Acid / Q000138:chemical synthesis* / Q000494:pharmacology / Q000031:analogs & derivatives; D013203:Staphylococcal Infections / Q000188:drug therapy; D013211:Staphylococcus aureus / Q000187:drug effects; D065093:beta-Lactamase Inhibitors; D047090:beta-Lactams / Q000494:pharmacology
D065093:beta-Lactamase Inhibitors; D047090:beta-Lactams; D019818:Clavulanic Acid; C033257:BL-P 2013; D000658:Amoxicillin; D010397:Penicillanic Acid