Benzopyranones with retro-amide side chains as (inhibitory) β-lactamase substrates

3-(N-Benzylcarbamoyl)-7-carboxy-3, 4-dihydro-2H-1-benzo-pyran-2-one and its 8-carboxy analogue have been synthesized and evaluated as potential (inhibitory) substrates of β-lactam-recognizing enzymes. These compounds are bicyclic δ-lactones with retro-amide (with respect to classical β-lactams) side chains. They were found to be comparably effective as substrates of typical class A, C and D β-lactamases as analogous benzopyranones bearing ‘normal’ amide side chains. The new 8-carboxy derivative, however, formed a much more (1000-fold) tightly-bound acyl-enzyme with a class C β-lactamase than did its ‘normal’ analogue, and thus provides a structural lead to new inhibitors of this class of β-lactamase.