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BACKGROUND: Potato virus Y (PVY) is a prominent representative of plant viruses. It can inflict severe damage upon Solanaceae plants, leading to global dissemination and substantial economic losses. To discover new antiviral agents, a class of planar chiral thiourea molecules through the key step of N‐heterocyclic carbene‐catalyzed nitrile formation reaction was synthesized with excellent optical purities for antiviral evaluations against plant virus PVY. RESULTS: The absolute configurations of the planar chiral compounds exhibited obvious distinctions in the anti‐PVY activities. Notability, compound (S)‐4u exhibited remarkable curative activities against PVY, with a half maximal effective concentration (EC50) of 349.3 μg mL−1, which was lower than that of the ningnanmycin (NNM) (EC50 = 400.8 μg mL−1). Additionally, The EC50 value for the protective effects of (S)‐4u was 146.2 μg mL−1, which was superior to that of NNM (276.4 μg mL−1). Furthermore, the mechanism‐of‐action of enantiomers of planar chiral compound 4u was investigated through molecular docking, defensive enzyme activity tests and chlorophyll content tests. CONCLUSION: Biological mechanism studies have demonstrated that the configuration of planar chiral target compounds plays a crucial role in the molecular interaction with PVY‐CP, enhancing the activity of defense enzymes and affecting chlorophyll content. The current study has provided significant insights into the roles played by planar chiralities in plant protection against viruses. This paves the way for the development of novel green pesticides bearing planar chiralities with excellent optical purities. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Developing methods to directly transform C(sp3) −H bonds is crucial in synthetic chemistry due to their prevalence in various organic compounds. While conventional protocols have largely relied on transition metal catalysis, recent advancements in organocatalysis, particularly with radical NHC catalysis have sparked interest in the direct functionalization of "inert" C(sp3) −H bonds for cross C−C coupling with carbonyl moieties. This strategy involves selective cleavage of C(sp3) −H bonds to generate key carbon radicals, often achieved via hydrogen atom transfer (HAT) processes. By leveraging the bond dissociation energy (BDE) and polarity effects, HAT enables the rapid functionalization of diverse C(sp3)−H substrates, such as ethers, amines, and alkanes. This mini‐review summarizes the progress in carbene organocatalytic functionalization of inert C(sp3)−H bonds enabled by HAT processes, categorizing them into two sections: 1) C−H functionalization involving acyl azolium intermediates; and 2) functionalization of C−H bonds via reductive Breslow intermediates. [ABSTRACT FROM AUTHOR]

The control of noncarbon stereogenic centers is of profound importance owing to their enormous interest in bioactive compounds and chiral catalyst or ligand design for enantioselective synthesis. Despite various elegant approaches have been achieved for construction of S‐, P‐, Si‐ and B‐stereocenters over the past decades, the catalyst‐controlled strategies to govern the formation of N‐stereogenic compounds have garnered less attention. Here, we disclose the first organocatalytic approach for efficient access to a wide range of nitrogen‐stereogenic compounds through a desymmetrization approach. Intriguingly, the pro‐chiral remote diols, which are previously not well addressed with enantiocontrol, are well differentiated by potent chiral carbene‐bound acyl azolium intermediates. Preliminary studies shed insights on the critical importance of the ionic hydrogen bond (IHB) formed between the dimer aggregate of diols to afford the chiral N‐oxide products that feature a tetrahedral nitrogen as the sole stereogenic element with good yields and excellent enantioselectivities. Notably, the chiral N‐oxide products could offer an attractive strategy for chiral ligand design and discovery of potential antibacterial agrochemicals. [ABSTRACT FROM AUTHOR]

Intermolecular pnictogen bonding (PnB) catalysis has received increased interest in non‐covalent organocatalysis. It has been demonstrated that organic electron‐deficient pnictogen atoms can act as prospective Lewis acids. Here, we present a catalytic approach for the asymmetric synthesis of chiral PIII compounds by combining intramolecular PnB interactions and carbene catalysis. Our design features a pre‐chiral phosphorus molecule bearing two electron‐withdrawing benzoyl groups, resulting in the formation of a σ‐hole at the P atom. X‐ray and non‐covalent interaction (NCI) analysis indicate that the model substrates exhibit intrinsic PnB interaction between the oxygen atom of the formyl group and the phosphorus atom. This induces a conformational locking effect, leading to the crystallization of the phosphorus substrate in a preferred conformation (P212121 chiral group). Under the catalysis of N–heterocyclic carbene, the aldehyde moiety activated by the pnictogen bond selectively reacts with an alcohol to yield the corresponding chiral monoester/phosphorus product with excellent enantioselectivity. This Lewis acidic phosphorus center, aroused by the non‐polarized intramolecular pnictogen bond interaction, assists in conformational and selective regulations, providing unique opportunities for catalysis and beyond. [ABSTRACT FROM AUTHOR]

Selective acylation of saccharides is an important basic transformation in saccharide chemistry. Synthetic strategies and protocols for saccharides can reach broad users when reagents are simple (inexpensive and readily available), green, and easy to handle. Herein, we disclose that the simplest boric acid, B(OH)3, can work as an effective promoter for C3–OH selective acylation of unprotected monosaccharides under the catalysis of a readily available N-heterocyclic carbene catalyst. Solvents such as THF from untreated commercial sources can be directly used. Mechanistically, the boric acid plays multiple roles in benefiting reaction yields and regioselectivities, including solubilizing the saccharide substrates by forming borate esters with the saccharides, shielding the C6–OH unit of the saccharides from acylation, and enhancing the selectivity between C3–OH and C2–OH reactions. We also found that the solvent has a profounder effect on the reaction yield and selectivity than the base. Selectively acylated saccharide products can be easily obtained with good-to-excellent yields and gram scales. Our study will encourage the further development of new synthetic strategies for saccharides that can reach beyond laboratory scales and to scientists not necessarily with expertise in organic synthesis. Compared to previous methods using aryl and alkyl boronic acids as modulating reagents, the use of boric acid provides a greener solution economically and environmentally. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]