Synthesis of Planar Chiral Compounds Containing α-Amino Phosphonates for Antiplant Virus Applications against Potato Virus Y

Abstract

An unprecedented study of the application of planar chiral compounds in antiviral pesticide development is reported. A class of multifunctional planar chiral ferrocene derivatives bearing α-amino phosphonate moieties was synthesized. These compounds, exhibiting superior optical purities, were subsequently subjected to antiviral evaluations against the notable plant pathogen potato virus Y (PVY). The influence of the absolute configurations of the planar chiral compounds on their antiviral bioactivities was significant. A number of these enantiomerically enriched planar chiral molecules demonstrated superior anti-PVY activities. Specifically, compound (<i>S</i>_p, <i>R</i>)-<b>9n</b> displayed extraordinary curative activities against PVY, with a 50% maximal effective concentration (EC₅₀) of 216.11 μg/mL, surpassing the efficacy of ningnanmycin (NNM, 272.74 μg/mL). The protective activities of compound (<i>S</i>_p, <i>R</i>)-<b>9n</b> had an EC₅₀ value of 152.78 μg/mL, which was better than that of NNM (413.22 μg/mL). The molecular docking and defense enzyme activity tests were carried out using the planar chiral molecules bearing different absolute configurations to investigate the mechanism of their antiviral activities against PVY. (<i>S</i>_p<i>, R</i>)-<b>9n</b>, (<i>S</i>_p<i>, R</i>)-<b>9o</b>, and NMM all showed stronger affinities to the PVY-CP than the (<i>R</i>_p<i>, S</i>)-<b>9n</b>. Investigations into the mechanisms revealed that the planar chiral configurations of the compounds played pivotal roles in the interactions between the PVY-CP molecules and could augment the activities of the defense enzymes. This study contributes substantial insights into the role of planar chirality in defending plants against viral infections.