Synthesis of Chalcone‐Derived Heteroaromatics with Antibacterial Activities

An efficient synthetic method of medicinally important chalcone‐derived heteroaromatics was proposed, which comprised of conjugate addition of ethyl acetoacetate to chalcones, followed by MnIII/CoII‐catalyzed oxidative deacetylation. Paal‐Knorr reactions of the resulting 1,4‐dicarbonyl compounds containing various phenyl substituents produced the corresponding 2‐carboethoxy‐3,5‐diphenyl furans, pyrroles, and thiophenes. The scope, mechanism, and electronic requirements for the phenyl substituents of chalcones in the key radical‐medicated deacetylation reaction were fully elucidated. Antibacterial activities of the 21 chalcone‐derived heteroaromatics were screened for Escherichia coli, Staphylococcus aureus, and Acinetobacter baumannii. The parent pyrrole 5 a showed most effective inhibition for E. coli and one third of the heteroaromatics exhibited significant inhibition for S. aureus at the concentration of 64 μg/mL. Chalcones were efficiently transformed into five‐membered heteroaromatics of furans, pyrroles and thiophenes by conjugate addition of ethyl acetoacetate, manganese(III)/cobalt(II)‐catalyzed oxidation, and Paal‐Knorr reactions. Antibacterial activities of the 21 chalcone‐derived heteroaromatics were screened for Escherichia coli, Staphylococcus aureus, and Acinetobacter baumannii. A half of the chalcone‐derived heteroaromatics exhibited antibacterial activities for S. aureus at the MIC of ≤128 μg/mL, while several of them were still potent for E. coli at the same concentration.