Multicomponent Approach to a Library of N-Substituted γ-Lactams.

Abstract

The γ-lactam motif is often found in naturally occurring compounds with diverse biological activities. We prepared a 28-member library of N-substituted γ-lactams following a single-pot, three-component Ugi reaction comprising bifunctional building block, l-glutamic acid methyl ester. The reaction tolerates structurally diverse carbonyl and isocyanide components providing a robust access to functionalized γ-lactams. Antimicrobial susceptibility testing, including agar well diffusion assay, serial microdilution broth assay, and antibiofilm activity testing, identified a potent compound with antibiofilm activity against Staphylococcus aureus ATCC 6538.