Fiaud's Acid, a novel organocatalyst for diastereoselective bis α-aminophosphonates synthesis with in-vitro biological evaluation of antifungal, antioxidant and enzymes inhibition potential.

(S, S)-1-hydroxy-1-oxo-2-c,5-t-diphenylphospholane or Fiaud's acid is used as a novel and effective chiral organocatalyst for bis α-aminophosphonates synthesis with excellent diastereoselectivity and yields within short reaction time. All synthesized bis α-aminophosphonates revealed a good to excellent antifungal capacity, where the six compounds 4a, 4b, 4e, 4h, 4k and 4l are the best fungicide inhibiting the growth of Fusarium oxysporumandBotrytis cinereaby 65% to 84% with IC50 values <0.02 mg/mL. Similarly, these six products exhibited a strong antioxidant effect, whereas a low inhibition activity was obtained with both AChE and BChE. Furthermore, they displayed a very weak inhibitory activity against tyrosinase except for the compound4l.These findings suggest a possible use of these compounds as synthetic pesticides with less hazardous effects with antioxidant, and anti-tyrosinase properties.

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

Eco-friendly and simple procedure has been developed for the synthesis of α-aminophosphonates 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 via Kabachnik-Fields reaction. This efficient method proceeds with catalytic amount, transition metal-free, at room temperature within short reaction time, giving the α-aminophosphonates derivatives (4a-r) in high chemical yields (up to 80%). Theoretical DFT calculations of three compounds (4p, 4q and 4r) 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. In silico 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.