2-Hydroxymethyl-18-crown-6 as an efficient organocatalyst for αaminophosphonates synthesized under eco-friendly conditions, DFT, molecular docking and ADME/T studies.

Eco-friendly and simple procedure has been developed for the synthesis of αaminophosphonates that act as topoisomerase II α-inhibiting anticancer agent, using 2-hydroxymethyl-18-crown-6 as an unexpected homogeneous organocatalyst in multicomponents reaction of aromatic aldehyde, aniline and diethylphosphite in one pot reaction. This efficient method proceeds with catalytic amount, transition metal-free, at room temperature within short reaction time, giving the αaminophosphonates derivatives in high chemical yields (up to 80%). Theoretical DFT calculations of three compounds and were carried out in a gas phase at CAM-B3LYP 6-31G (d,p) basis set to predict the molecular geometries and chemical reactivity descriptors. The frontier orbital energies (HOMO/LUMO) were described the charge transfer and used to predict structure-activity relationship study. Molecular electrostatic potential (MEP) has also been analyzed. Molecular docking studies are implemented to analyze the binding energy and compared with Adriamycin against 1ZXM receptor which to be considered as antitumor candidates. pharmacological ADMET properties as Drug likeness and oral activity have been carried out based on Lipinski's rule of five.Communicated by Ramaswamy H. Sarma.