Synthesis of N-Functionalized Lactams

Synthesis of N-Functionalized Lactams

Author: ChemistryViews

Five-membered ring lactams, γ-lactams, are important structural motifs in biologically active natural products, but γ-lactams that are substituted at the 1-position (nitrogen) are less common in drug leads. A survey of γ-lactams of in preclinical and clinical development showed a nearly two-to-one ratio of N–H lactams (unsubstituted) over their substituted counterparts. This is perhaps due to synthetic limitations.

Jared Shaw and co-workers, University of California – Davis, USA, have reported a multicomponent methodology for the synthesis of unsubstituted γ-lactams and their subsequent N-functionalization. By including ammonium acetate as the starting material in a previously reported four component reaction (4CR), the team demonstrated a range of N–H lactam structures could be produced. These substrates could then be functionalized at nitrogen through acylation or arylation to provide structural diversity unavailable through the original 4CR.

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