6-(1-Hydroxyalkyl)penam sulfone derivatives as inhibitors of class A and class C β-lactamases II

Two stereoselective processes for the synthesis of novel 3,6-disubstituted penam sulfone derivatives were developed. One 6β-(1-hydroxyethyl) and four 6β-hydroxymethyl penam sulfone derivatives were synthesized. All four 6β-(hydroxymethyl)penam sulfone derivatives demonstrated good IC50 against both TEM-1 and AmpC β-lactamases. Of these, 6β-hydroxymethyl penam sulfone derivative 25 was the most active inhibitor which was able to restore the activity of piperacillin in vitro and in vivo against both TEM-1 and AmpC β-lactamases producing organisms.