N-aryl modification in-lactam: Design and synthesis of novel monocyclic-lactam derivatives as inhibitor for bacterial propagation

摘要

In search of novel γ-lactam antibacterial agents as non-lactam mimics of some γ-lactam antibiotics, N-aryl modification in the γ-lactam ring has been made to synthesize compounds 4-8 in two to six steps. Compound 4 was synthesized using the intermolecular Michael addition of diethyl N-(6-coumarinyl)-2-aminomalonate and 3-aryl/(2-heteroaryl)acryloyl chloride followed by intramolecular amidification. Hydrolysis and stereoselective decarboxylation of 4 resulted in the formation of trans-γ-lactam carboxylic acids (5), which on side chain homologation followed by saponification of the intermediate γ-lactam monoester (7) afforded γ-lactam carboxylic derivatives 8. Moderate to good bacterial growth inhibition was observed for some of the synthesized compounds against E. coli and S. aureus.