Synthesis, spectral, stereochemical, biological, molecular docking and DFT studies of 3-alkyl/3,5-dialkyl-2r,6c-di(naphthyl)piperidin-4-one picrates derivatives

Abstract A new series of 3-alkyl/3,5-dialkyl-2r,6c-di(naphthyl)piperidin-4-one picrates (1-6) were synthesized their chemical structures were confirmed by elemental analysis, FT-IR, 1H and 13C NMR and mass spectral techniques and for compound 4 was characterized by HOMOCOSY, HSQC, HMBC, NOESY, and DEPT NMR spectral techniques. From the NMR spectral data, the observed chemical shifts and coupling constants suggested that compounds (1-6) adopt a normal chair conformation with equatorial orientation of all the naphthyl groups at C-2 and C-6 and alkyl group at C-3 and C-5 and from the 1H chemical shifts H-5a and H-3a have a higher magnitude than H-5e. This is due to 1,3 diaxial interaction between axial NH proton and axial protons at C-3 and C-5. The synthesized compounds were screened for their bacterial activity against Escherichia coli, Staphylococcus aureus, Bacillus.subtilis, Vibreo cholerae and Pseudomonas aeruginosa and fungal activity against Candida albicans, Aspergillus niger, Aspergillus flavus and Trichophyton rubrum. All the compounds showed good antibacterial and antifungal activities. The optimized molecular structure of the synthesized compounds (1-6) were studied by using DFT/B3LYP/6-311++G(d,p) basis set. The calculated electrical dipole moment (µ) and first hyperpolarizability (βo) values shows that all the molecules might have nonlinear optical (NLO) behavior. The HOMO-LUMO transition implies that intra-molecular charge transfer takes place within the molecule. Molecular electrostatic potential (MEP) surface is used to understand the reactive sites of a molecule. To establish information about the molecular interactions between protein and this novel compound theoretically, docking studies were carried out in detail.