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.

中文翻译：

---

轴向手性噻嗪衍生物的设计、对映选择性合成及其对马铃薯Y病毒的抗病毒活性

通过N-杂环卡宾（NHC）催化的对映选择性[3 + 3]环化成功合成了一系列具有（R）和（S）构型轴向手性的新型噻嗪衍生物，及其作为抗植物病毒剂的潜力对马铃薯 Y 病毒 (PVY) 进行了评估。生物活性结果表明，大多数手性噻嗪衍生物表现出显着的抗PVY活性。值得注意的是，化合物( S ) -3g在500μg/mL的浓度下对PVY表现出显着的58%灭活效果，略超过宁南霉素(NNM)的57%的效果。此外，( S ) -3g的治疗活性为57%，优于NNM (53%)。分子对接研究初步揭示了两种不同对映体（R）或（S）-3g针对PVY的独特生物学特性，其中单一对映体（S）-3g与PVY-CP形成了更稳定的相互作用，如下式所示：与 ( R )- 3g ( −36.9 kcal/mol) 相比，其结合自由能较低 (−41.18 kcal/mol) 。这项研究的结果涉及一类新型轴向手性噻嗪衍生物，将激发手性杂环化合物的进一步开发，作为保护植物病毒感染的潜在候选药物。