Design, enantioselective synthesis, and antiviral activities against potato virus Y of axially chiral thiazine derivatives

Abstract

A series of novel thiazine derivatives featuring axial chirality in both (R) and (S) configurations were successfully synthesized by N‐heterocyclic carbene (NHC)‐catalyzed enantioselective [3 + 3] annulations, and their potential as anti‐plant virus agents against potato virus Y (PVY) was evaluated. Biological activity results demonstrated that most of these chiral thiazine derivatives exhibited significant activities against PVY. Notably, compound (S)‐3g displayed a remarkable 58% inactivation effect against PVY at a concentration of 500 μg/mL, slightly surpassing the effectiveness of Ningnanmycin (NNM) at 57%. Additionally, (S)‐3g exhibited curative activity of 57%, which is superior to NNM (53%). Molecular docking studies revealed preliminary insights into the distinct biological properties of the two different enantiomers, (R) or (S)‐3g against PVY, wherein single enantiomer (S)‐3g formed a more stable interaction with PVY‐CP, as indicated by its lower binding free energy (−41.18 kcal/mol) compared to (R)‐3g (−36.9 kcal/mol). The findings in this study with a new class of axially chiral thiazine derivatives shall inspire further development of chiral heterocycles as potential drug candidates for the protection of plant virus infections.

Application of Asymmetric Catalysis in Chiral Pesticide Active Molecule Synthesis

“…It is pleasing that most of the chiral thiazine compounds 18 displayed promising in vivo activities against PVY at 500 μg/mL, with noticeable differences in antiviral activities observed among thiazine derivatives with different (R)/(S) configurations. 85 Particularly, compound (R)-18b exhibited a 60% curative rate against PVY, while compound (R)-18c demonstrated significantly higher protective activity against PVY (61%) compared to those of its corresponding enantiomer (24%) and racemate (41%). Compound (S)-18d showed comparable curative activity (57%), protective activity (48%), and inactivation activity (58%) against PVY to ningnanmycin (NNM, 53%, 54% and 57%, respectively).…”

“…As for the axially chiral thiazine derivatives 18 and chiral 2-pyranylphosphonate products 32 mentioned above, Chi and co-workers also systematically studied the antiviral activities of these two series of novel chiral heterocycles using the half-leaf scorched spot method (Figure ). It is pleasing that most of the chiral thiazine compounds 18 displayed promising in vivo activities against PVY at 500 μg/mL, with noticeable differences in antiviral activities observed among thiazine derivatives with different ( R )/( S ) configurations . Particularly, compound ( R )- 18b exhibited a 60% curative rate against PVY, while compound ( R )- 18c demonstrated significantly higher protective activity against PVY (61%) compared to those of its corresponding enantiomer (24%) and racemate (41%).…”