Development of axially chiral urazole scaffolds for antiplant virus applications againstpotato virus Y

Abstract

BACKGROUND Potato virus Y (PVY) was first discovered by Smith in 1931 and is currently ranked as the fifth most significant plant virus. It can cause severe damage to plants from the family Solanaceae, which results in billions of dollars of economic loss worldwide every year. To discover new antiviral drugs, a class of multifunctional urazole derivatives bearing a stereogenic CN axis were synthesized with excellent optical purities for antiviral evaluations against PVY. RESULTS The absolute configurations of the axially chiral compounds exhibited obvious distinctions in antiviral bioactivities, with several of these enantio‐enriched axially chiral molecules showing excellent anti‐PVY activities. In particular, compound (R)‐9f exhibited remarkable curative activities against PVY with a 50% maximal effective concentration (EC50) of 224.9 μg mL−1, which was better than that of ningnanmycin (NNM), which had an EC50 of 234.0 μg mL−1. And the EC50 value of the protective activities of compound (R)‐9f was 462.2 μg mL−1, which was comparable to that of NNM (442.0 μg mL−1). The mechanisms of two enantiomer of the axially chiral compounds 9f were studied by both molecule docking and defensive enzyme activity tests. CONCLUSION Mechanistic studies demonstrated that the axially chiral configurations of the compounds played significant roles in the molecule PVY‐CP (PVY Coat Protein) interactions and could enhance the activities of the defense enzymes. The (S)‐9f showed only one carbon–hydrogen bond and one π–cation interaction between the chiral molecule and the PVY‐CP amino acid sites. In contrast, the (R)‐enantiomer of 9f exhibited three hydrogen bonding interactions between the carbonyl groups and the PVY‐CP active sites of ARG157 and GLN158. The current study provides significant information on the roles that axial chiralities play in plant protection against viruses, which will facilitate the development of novel green pesticides bearing axial chiralities with excellent optical purities. © 2023 Society of Chemical Industry.

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

“…We extracted the PVY virus from PVY-infected tobacco K326 leaves using the reported methods. 32 We conducted an antiviral test against PVY with planar chiral compounds on 40-day-old Chenopodium amaranticolor (C. amaranticolor) plants using the half-leaf method. All antiviral activity tests were conducted in triplicate.…”

“…We extracted the PVY virus from PVY-infected tobacco K326 leaves using the reported methods . We conducted an antiviral test against PVY with planar chiral compounds on 40-day-old Chenopodium amaranticolor (C.…”

Application of Asymmetric Catalysis in Chiral Pesticide Active Molecule Synthesis

“…59 To investigate the potential applications of axially chiral molecules in preventing and treating plant diseases induced by PVY infections, Chi and co-workers disclosed a carbenecatalyzed atroposelective [3 + 2] annulation reaction for the efficient synthesis of chiral heteroatom-rich urazoles 47 with C−N axial chirality. 86,87 The reaction employed ynals 16 and 4-arylurazoles 46 as the starting materials. A variety of axially chiral pyrazolo[1,2-a]triazole derivatives, bearing various substituents and substitution patterns, were obtained in generally good to excellent yields and enantioselectivities.…”

Design, synthesis and Anti‐PVY activity of planar chiral thiourea derivatives incorporated with [2.2]Paracyclophane

“…The R-enantiomer exhibited a better curative effect, with values of 72%, surpassing the efficacy of the S-configuration of ⊍-aminophosphonates against CMV. Recently, Chi and coworkers 35 disclosed an application of novel axially chiral urazole derivatives to prevent plants from PVY infection. The enantiomers of urazole derivatives showed different anti-PVY activity, highlighting the significance of axial chirality.…”