A Newly Synthesized β-amino-α, β-unsaturated Ketone Derivative of β-himachalene: Structural, NBO, NLO, and Molecular Docking Studies

Abstract

In the current study, a new β-amino-α,β-unsaturated ketone-based himachalene ((1S,3R,8R)-9-amino-2,2-dichloro-3,7,7,10-tetramethyltricyclo[6.4.0.01,3]dodec-9-en-11-one) (4) was synthesized from β-himachalene (1) extracted from essential oil of Atlas Cedar. The β-amino-α, β-unsaturated ketone product (4) was characterized by 1D NMR (1H, 13C) and 2D NMR (HSQC, COSY, NOESY), FTIR analysis, and single-crystal X-ray diffraction. The title compound, C16H23Cl2NO, crystallizes with two molecules in the asymmetric unit with similar conformations. One of the two molecules is characterized by chlorine and one-methyl position disorder. In the crystal, intermolecular N—H…O hydrogen bonds lead to forming a three-dimensional framework. In addition, the molecular structure of the title compound was examined by Hirshfeld topology analysis and Density Functional Theory (DFT) using B3LYP calculations at 6-311+G(d,p) level. The optimized structure parameters were compared with the experimental result, an excellent correlation between theoretical structures parameters and experimental values was found. The natural bond orbitals (NBO) analysis and the first-order hyperpolarizability were also performed. Moreover, two biological activities were examined for product 4 against Acetylcholinesterase and Cytochrome P450 3A4, which bind to similar fragments with molecular docking. We find good scores and binding affinity of our molecule to link to these two proteins.