Synthesis and biological evaluation of some drug-like scaffolds of benzo-and pyrido-fused medium-sized n-heterocycles obtained via intramolecular Friedel-Crafts acylation reactions

An unprecedented, concise and environmentally-friendly protocol for the synthesis of benzo- and pyrido-annulated azocinones, azoninones and azecinones 8a-h via Friedel-Crafts reactions is described. These simple and efficient procedures involve cycliacylations of heterocyclic esters 7a-h in the presence of catalytic amount of AlCl3/CH3NO2 or TfOH or PPA catalysts as the key step. Starting amides 3a-d were readily obtained by coupling reactions of acryloyl chlorides 2ab with pyridin-2-amines 1a, b. Our developed strategy offers some high selectivity reactions, mild reaction conditions and easy access to complex medium-sized N-heterocycles in moderate to good yields. All tetracyclic fused compounds have been screened for antimicrobial activity.