Synthesis of designed new 1,3,4-oxadiazole functionalized pyrano [2,3-f] chromene derivatives and their antimicrobial activities.

Diethyl 2-(((4-methyl-2-oxo-2H-chromen-7-yl)oxy)methylene)malonate (2) was synthesized from coumarin 1 and diethyl ethoxymethylene malonate in ethanol, followed by cyclization in diphenyl ether to give chromene-9-carboxylate (3). Sugar hydrazones 5a-c were formed by reacting hydrazide 4 with D-galactose, D-mannose, and D-xylose, then acetylated to per-O-acetyl derivatives 6a-c. Heating 5a-c with acetic anhydride at 100 °C gave oxadiazolines 7a-c. Compound 8, obtained by refluxing 4 with carbon disulfide, was alkylated to 9 or reacted to give 10. Further reactions yielded acetoxy derivative 13 and hydroxy derivative 14. Compounds 17a-e and 18a-e were synthesized using thiomorpholinophenyl ureido/thioureido-s-triazine. These compounds were characterized and evaluated for antibacterial activity against Gram (+ve) bacteria (B. subtilis, S. aureus) and Gram (-ve) bacteria (E. coli, P. aeruginosa) in addition to yeast-like fungi (C. albicans). Compounds 11, 13, 15, 16, 17c-e, and 18a-e showed the highest antibacterial activity. Molecular docking was performed to study their binding with transpeptidases.