Benzopyranones with retro-amide side chains as (inhibitory) beta-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 beta-lactam-recognizing enzymes. These compounds are bicyclic delta-lactones with retro-amide (with respect to classical beta-lactams) side chains. They were found to be comparably effective as substrates of typical class A, C and D beta-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 beta-lactamase than did its 'normal' analogue, and thus provides a structural lead to new inhibitors of this class of beta-lactamase.
Adediran
S A
SA
Department of Chemistry, Wesleyan University, Middletown, CT 06459, USA.
Cabaret
D
D
Lohier
J-F
JF
Wakselman
M
M
Pratt
R F
RF
D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry*; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry; D001578:Benzopyrans / Q000138:chemical synthesis* / Q000737:chemistry; D016972:Enterobacter cloacae; D006868:Hydrolysis; D007700:Kinetics; D013211:Staphylococcus aureus; D013302:Streptomyces; D018440:beta-Lactam Resistance; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases / Q000737:chemistry
D000577:Amides; D000900:Anti-Bacterial Agents; D001578:Benzopyrans; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases