Synthesis, Antimicrobial Evaluation, DFT, and Molecular Docking Studies of Pyrano 4,3‐b Pyranone and Pyrano2,3‐bPyridinone Systems

Abstract Dehydroacetic acid (DHA) was utilized as a fundamental precursor in the synthesis of novel pyrano 4,3‐ b pyran and pyrano 2,3‐ b pyridine systems. Whereas, a new series of fused polyheteronuclear systems was achieved through the reaction of DHA with active methylene compounds such as malononitrile and pyrazolone. Whereas, the treatment of DHA 1 with cyclic ketones involving cyclohexanone and cyclododecanone afforded annulated tricyclic system 6 and spiro hybrid molecule 7 . Also, the reaction of DHA 1 with cyanoacetamide derivatives 8 and 11 yielded their corresponding novel pyrano 2,3‐ b pyridine‐6‐carbonitrile frameworks 9 and 12 , respectively. Also, in silico predictive theoretical molecular docking studies for bioactive synthesized scaffolds against both HER2 and 6BBP displayed an optimistic result for compounds 2 b , 5 , 9 , and 12 highlighting their expediency as up–and–coming candidates for future preclinical trials. Additionally, all compounds were assessed as antibacterial agents against various types of four candidates of bacteria in the presence of ampicillin as a reference. Notably, compounds 6 , 7 , and 12 showed promising antibacterial potential against Bacillus subtilis with activity indexes (69.6, 91.3, and 82.6 %), respectively.