Synthesis of a macrocyclic and medium-sized ring lactam library using cascade ring expansion reactions

A versatile approach for the synthesis of a diverse library of macrocyclic and medium-sized ring lactams is described. Up to three-sequential synthetic steps were used, starting with a conjugate addition/ring expansion cascade, followed by side-chain and ring elaboration steps. The library was tested for antibacterial activity against Staphylococcus aureus and Escherichia coli. Although no novel antibacterial agents were uncovered in this study, the utility of the approach to quickly generate diverse lactam libraries for bioassay is confirmed.