Structure-based efforts to optimize a non-β-lactam inhibitor of AmpC β-lactamase.

β-Lactams are the most widely prescribed class of antibiotics, yet their efficacy is threatened by expression of β-lactamase enzymes, which hydrolyze the defining lactam ring of these antibiotics. To overcome resistance due to β-lactamases, inhibitors that do not resemble β-lactams are needed. A novel, non-β-lactam inhibitor for the class C β-lactamase AmpC (3-[(4-chloroanilino)sulfonyl]thiophene-2-carboxylic acid; Ki 26μM) was previously identified.

Photochemical synthesis of aldehydes in the solid phase.

A substituted anthraquinone (AQ), previously shown to photochemically generate benzaldehyde in methanol solution, was attached to a commercially available resin via an 11 carbon tether and an amide bond. Photolysis of the polymer-bound AQ with visible or 350 nm UV light resulted in the formation of benzaldehyde in yields of 50-55% as determined by HPLC. The phenolic positions in the polymer were then alkylated using benzyl bromide and 1-iodo-3-(4-nitrophenyl)propane in a coupling reaction with K(2)CO(3) as a base and a solution-phase proton shuttle.