Synthesis, XRD structure, spectroscopy, hirshfeld surface analysis, and computational and in silico ADME studies of 13-(piperidinyl)parthenolid-9-one

Abstract

In this work, 13-(piperidinyl)parthenolid-9-one has been synthesized, elucidated by ¹H- and ¹³C-NMR spectral data, and confirmed by X-ray diffraction. In the crystal structure, the ten-membered ring displays an approximate chair-chair conformation, whereas the five-membered furan ring has an envelope conformation. The furan ring is linked to a 1-ethyl­piperidine in which the piperidine cycle adopts a perfect chair conformation. The mean plane of the furane ring is nearly perpendicular to that of the piperidine cycle as indicated by the dihedral angle between them of 83.0 (3)°. Two hydrogen bonds connect the molecules and ensure crystal cohesion. The Hirshfeld surface analysis of the crystal structure indicates that the most important contributions are H⋯H and O⋯H/H⋯O interactions. The molecular geometry in the ground state was calculated by using the HF and DFT methods with 6-31G(d,p) and 6-311G(d,p) basis sets and compared with the experimental data. Besides, molecular electrostatic potential (MEP), Mulliken atomic charges and natural bond charges were computationally determined with the same basis sets. The thermodynamic properties have been obtained from the theoretical vibrations. Finally, computational ADME studies of the title compound were performed and found to have good oral bioavailability.