Wu-Lin Yang

An iridium-catalyzed allylation/esterification cascade reaction of spirotetramic acid derivatives has been developed, affording chiral 3-allylic spirotetramic acid ester derivatives with excellent enantioselectivity (94-99% ee) in moderate to high yields (43-97%). Meanwhile, a sequential iridium- and cinchona alkaloid-catalyzed double allylations reaction was established, yielding chiral 3-allylic spirotetramic acid derivatives bearing two stereogenic centers with excellent enantioselectivity (99% ee) and moderate to high diastereoselectivity (4:1 to >20:1 dr) in moderate to good yields (43-70%). The target compound 4d exhibited promising insecticidal activity against Aphis craccivora, with the activity of (S)-4d (LC₅₀ = 0.094 g·L^-1) being significantly higher than that of (R)-4d (LC₅₀ = 0.174 g·L^-1) and its racemate (LC₅₀ = 0.178 g·L^-1).

To overcome the high toxicity of etoxazole to aquatic invertebrates and its limited structural diversity while preserving its potent acaricidal activity, we successfully designed and synthesized 27 novel 2,4,5-trisubstituted oxazoline derivatives and systematically assessed their acaricidal activity. Among these, compounds 12q (LC₅₀ = 0.84 mg/L) and 12u (LC₅₀ = 0.74 mg/L) exhibited moderate ovicidal activity. Notably, compound 12aa exhibited good ovicidal (LC₅₀ = 0.14 mg/L) and larvicidal activities (LC₅₀ = 0.09 mg/L), highlighting its potential as a lead compound. Potential surface calculations and molecular docking studies indicated that differences in the lipophilicity of oxazoline derivatives as well as variations in their binding conformations within chitin synthase 1 of Tetranychus cinnabarinus (TcCHS1), might account for the observed differences in biological activity. Additionally, density functional theory (DFT) calculations further supported the design rationale. Zebrafish toxicity assays revealed that compounds 12q, 12u, and 12aa exhibited significantly lower acute toxicity, underscoring their potential as a safer alternative for pest management. Our current study has identified a novel 2,4,5-trisubstituted oxazoline scaffold with moderate acaricidal activity and reduced toxicity to zebrafish.

The development of succinate dehydrogenase inhibitors (SDHIs) is crucial for ensuring sustainable food production. This study introduces a novel class of aryl oxime ester derivatives to improve antifungal activity. In vitro experiments showed that compounds with methylene linkers had better biological activity. Compound A7 exhibited potent inhibition against F. graminearum (EC₅₀ = 1.07 μg/mL), outperforming fluxapyroxad (FLU; EC₅₀ = 5.15 μg/mL). In vivo trials demonstrated 67.14% suppression at 100 μg/mL, indicating field potential. Enzymatic inhibition studies confirmed the inhibition of A7 (IC₅₀ = 34.33 μM), approaching FLU (IC₅₀ = 15.95 μM). Docking study indicate that the A7 carbonyl can form hydrogen bonds similar to those formed by FLU, while the π-π interaction of A7 plays a key role in SDH binding. This structural synergy underscores the role of oxime esters in optimizing SDHI binding affinity. This work establishes aryl oxime ester as an effective skeleton for SDHI optimization, providing a promising scaffold for future development.

Using plant-released volatiles to attract and control pest moths is a key approach to pest management strategies. β-Phellandrene (β-Phe) has been proven to be attractive to the yellow peach moth (Conogethes punctiferalis). Herein, we designed and synthesized 25 structural analogues of β-Phe and identified four compounds (3a, 3d, 4a, and 4g) with high attraction activity. Among them, the ester-containing compound 4g exhibited the highest attraction rate (76.6%) at a concentration of 10 mg/mL, whose stability and accessibility are both superior to β-Phe. Molecular docking results revealed that the target compounds strongly bound to the general odorant-binding protein 1 (GOBP1) of C. punctiferalis via hydrophobic interactions and π-π stacking. Quantum calculations demonstrated that ester groups optimize the electrostatic potential and introduce hydrogen-bonding sites. These findings elucidate structure-activity relationships and molecular recognition mechanisms of volatile attractants, offering insights for eco-friendly pest management strategies.

To develop structurally novel spirocyclic tetramic acid insecticides and acaricides with high activity and low toxicity, a rational molecular modification was implemented by introducing a thiocyanato (SCN) group at the α-position of the spirocyclic tetramic acid bioactive intermediates. These new α-SCN-substituted tetramic acid derivatives were synthesized through an electrophilic thiocyanation reaction. Bioassays revealed that compounds C16 (LC₅₀ = 0.379 mg/L) and C20 (LC₅₀ = 0.410 mg/L) exhibited superior acaricidal activity against Tetranychus cinnabarinus compared to spirodiclofen (LC₅₀ = 0.520 mg/L). Compound C1 exhibited insecticidal activity against Aphis craccivora (LC₅₀ = 0.663 mg/L), which was similar to that of spirotetramat (LC₅₀ = 0.503 mg/L). Compounds C16 and C28 displayed remarkable herbicidal activity at 500 g ai/ha against gramineous weeds (such as Digitaria sanguinalis, Echinochloa crusgalli, and Leptochloa chinensis) with broad-spectrum weed control potential. Embryotoxicity assessment in zebrafish (Danio rerio) indicated significantly reduced developmental toxicities for C1 (LC₅₀ = 13.1 mg/L) and C16 (LC₅₀ = 6.86 mg/L) compared to those for spirotetramat (LC₅₀ = 2.73 mg/L) and spirodiclofen (LC₅₀ = 0.334 mg/L). Systemic translocation bioassay demonstrated that highly bioactive compounds C1 and C16 have systemic translocation similar to that of spirotetramat. This study successfully developed a series of spirocyclic tetramic acid derivatives with high bioactivity and lower aquatic toxicity through the rational incorporation of the SCN group. The findings provide a valuable approach for the innovation of environmentally friendly pesticide molecules.

A series of neonicotinoid analogues with 1,2‐dihydropyridine scaffold were synthesized by the novel annulation reaction. Bioassay indicated that some compounds exhibited good insecticidal activity against Aphis craccivora at a concentration of 100 mg/L, and the substituents on the phenyl group have a great influence on insecticidal activity. Especially, the LC₅₀ values of compounds A3 and A19 were 17.089 and 4.792 mg/L, respectively. Molecular docking results revealed that compound A19 bound to Lymnaea stagnalis acetylcholine binding protein via H‐bonds with the residues of Leu102, Val114, and Arg55. These results proposed a promising guide for the design of neonicotinoid analogues with 1,2‐dihydropyridine scaffold.

The scaffold hopping strategy of chain extension is widely used in medicines and pesticides, many of which have introduced alkynes to increase rigidity and activity. Therefore, an alkyne molecule is introduced into the biphenyl structure to form alkyne-containing difluoropyrazole derivatives. Most of the compounds had excellent activity in in vitro activity tests against Rhizoctonia solani. The EC₅₀ values of compounds A1, A13, A15, and A18 were 0.0214, 0.0189, 0.0223, and 0.0173 mg/L, respectively, which were similar to fluxapyroxad (EC₅₀ = 0.0237 mg/L). Activity tests in vivo revealed that compound A12 still had 57.1% control against R. solani at 5 mg/L. The inhibition effects of compounds A12 and A16 against succinate dehydrogenase were 3.58 and 2.22 μM, respectively, better than fluxapyroxad (IC₅₀ = 4.24 μM). The mode of action of these compounds was further explored by molecular docking and scanning electron microscopy analysis, and the results were found to be similar to those of fluxapyroxad. These results demonstrate a new concept of introducing alkyne-based chain extension in succinate dehydrogenase inhibitor fungicides.

A cinchona alkaloid-catalyzed asymmetric α-difluoromethylketone thiolation of β-ketoesters with the electrophilic phthalimide-SCF₂COAr reagent was developed, affording α-difluoromethylthiolated ketones with moderate to high enantioselectivities.

The modification of active ingredients with a trifluoromethyl group represents a significant approach for the discovery of highly active pesticides. Herein, we developed a novel [3 + 3] annulation reaction of neonicotinoid precursors and trifluoromethyl-α,β-ynones and synthesized a series of CF₃-containing polycyclic neonicotinoid derivatives in high efficiency. The insecticidal activity results indicated that most of the target compounds showed good insecticidal activities against Aphis craccivora and Nilaparvata lugens at a concentration of 100 mg/L. In particular, compounds 3o and 4k had LC₅₀ values of 1.53 and 1.47 mg/L against A. craccivora, respectively, which were comparable to that of imidacloprid (LC₅₀ = 1.30 mg/L). The honeybee toxicity predictive model also indicated the potential low honeybee toxicity of target compounds 3o and 4k. The molecular docking study revealed that the target compounds 3o and 4k exhibited a favorable binding mode with the Lymnaea stagnalis acetylcholine-binding protein and the R55T-mutated resistant model.

As one of the most significant insecticides, neonicotinoids have played a pivotal role in crop protection and public sanitation. However, the high resistance and bee toxicity of neonicotinoid insecticides have attracted considerable attention. Herein, a series of neonicotinoid compounds with conjugated diene moieties were synthesized through the cascade allylation/isomerization reaction. Most of the target compounds exhibited excellent insecticidal activities against Aphis craccivora, and some compounds exhibited good insecticidal activities against Mythimna separata. In particular, compound A15 showed outstanding insecticidal activity against A. craccivora (LC₅₀ = 0.15 mg/L), which was superior to that of imidacloprid (LC₅₀ = 0.36 mg/L). In addition, this candidate exhibited minimal cross-resistance to imidacloprid. The acute contact toxicity tests on Apis mellifera suggested that compound A15 was 10 times less toxic than imidacloprid. Electrophysiological experiments and molecular docking studies indicated that compound A15 exerted its insecticidal effects by interfering with nicotinic acetylcholine receptors. This work identifies a novel conjugated diene neonicotinoid candidate with significant potential for further development.