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.