Synthesis and Antimicrobial Evaluation of a New Series of Heterocyclic Systems Bearing a Benzosuberone Scaffold

摘要

A series of novel benzosuberone derivatives were synthesized and evaluated as antimicrobial agents by using substituted benzosuberone derivatives >1a,>b as starting materials. Treatment of >1a,>b with phenyl isothiocyanate in dimethylformamide was followed by treatment with cold HCl solution to afford the thioamides >4a,>b, which was reacted with methyl iodide to obtain methylated products >5a,>b. Cyclocondensation of >4a,>b with chloroacetone >6 and phenacyl chloride >7 gave the corresponding thiophene derivatives >9a–>c. Reaction of >4a,>b with C-acetyl-N-arylhydrazonoyl chlorides >14a and >14b in boiling EtOH in the presence of triethylamine, afforded the corresponding 1,3,4-thiadiazoline derivatives >16a–>d. The thioamides >4a,>b were reacted with C-ethoxycarbonyl-N-arylhydrazonoyl chlorides >18a,>b which afforded 1,3,4-thiadiazoline derivatives >19a–>d. The benzosuberones >1a,>b were treated with 3-mercaptopropanoic acid to give compounds >21a,>b, which were cyclized to tricyclic thiopyran-4(5H)-one derivatives >22a,>b. The latter compounds >22a,>b were reacted with 3-mercaptopropanoic acid to give compounds >23a,>b, which were cyclized tetracyclic ring systems >24a,>b. Finally, compounds >24a,>b were oxidized using hydrogen peroxide under reflux conditions to afford the oxidized form of the novel tetracyclic heterogeneous ring systems >25a,>b. The newly synthesized compounds were screened for antimicrobial activities. The structures of new compounds were characterized by ¹H-NMR, ¹³C-NMR, IR, and EI-MS.