Synthesis and .beta.-lactamase inhibitory properties of 2.beta.-(chloromethyl)-2.alpha.-methylpenam-3.alpha.-carboxylic acid 1,1-dioxide

Abstract
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 is a potent inhibitor of various bacterial .beta.-lactamases and protects amoxicillin from .beta.-lactamases in in vitro and in vivo systems.