Synthesis and .beta.-lactamase inhibitory properties of 2.beta.-(chloromethyl)-2.alpha.-methylpenam-3.alpha.-carboxylic acid 1,1-dioxide
摘要:
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.
Synthesis and .beta.-lactamase inhibitory properties of 2.beta.-(chloromethyl)-2.alpha.-methylpenam-3.alpha.-carboxylic acid 1,1-dioxide
作者:William J. Gottstein、Leonard B. Crast、Robert G. Graham、Ute J. Haynes、Donald N. McGregor
DOI:10.1021/jm00144a034
日期:1981.12
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.