N-Benzyl-2,7-diphenyl-1,4-diazepan-5-one analogues: Synthesis, spectral characterization, stereochemistry, crystal structure and molecular docking studies

Three novel N-benzyl-2,7-diphenyl-1,4-diazepan-5-ones 10–12 have been synthesized via two routes starting from 2,7-diphenyl-1,4-diazepan-5-ones 4–6 and N-benzyl-2,6-diphenylpiperidin-4-ones 7–9. The structural characterization and conformational analysis of these synthesized compounds have been carried out using IR, mass and 1H, 13C, DEPT-135 and 2D (COSY and HSQC) NMR spectral techniques. The N-benzyldiazepan-5-one 10 is found to prefer chair conformation with equatorial orientation of alkyl and phenyl groups while N-benzyldiazepan-5-ones 11 &12 prefer to adopt twist-boat conformation with phenyl rings at C-2 & C-7 occupying equatorial and pseudo-axial orientations, respectively. The single crystal X-ray structure of compound 12 has been determined which also supports the twist-boat conformation. In silico molecular docking study has also been performed and the results show that the compounds 10–12 might exhibit inhibitory activity against HIV-1 protease. All the compounds are screened for their antibacterial activity against three bacterial strains (Staphylococcus aureus, Escherichia coli and Bacillus cereus) and only compound 11 shows moderate activity. [Display omitted] •Three novel N-benzyl-1,4-diazepan-5-ones have been synthesized and characterized.•In solution state, 10 prefers CE conformation of the parent.•Interestingly 11 &12 prefer twist-boat conformation.•X-ray crystal structure of 12 shows twist-boat conformation.•Docking studies confirm the binding of active compounds 10–12 with HIV-1 protease.