Huizhe Lu

Avermectin degrades rapidly under UV light, limiting its field efficacy to 3-5 days. This necessitates frequent reapplication, increasing costs and raising concerns about residues and ecological risks. In this study, a novel class of photoactivatable avermectin derivatives was synthesized via structural modification by introducing an o-nitrobenzyl group. The aim was to enhance systemic translocation following root application by improving compound mobility within the plant─thereby preventing rapid photodegradation under light exposure, and achieving a sustained-release effect. Based on insecticidal activity studies and transport experiments, this study developed two highly active derivatives. These compounds not only maintain high insecticidal activity but also, according to their enhanced systemic mobility and sustained concentration profiles observed in plants, show the potential to significantly prolong the effective duration in practical applications. Computational chemistry analyzed both the photodegradation mechanism of o-nitrobenzyl ester and the interactions of its derivatives with target proteins.

Triazolopyrimidine sulfonamide herbicides, a prominent class of acetohydroxyacid synthase (AHAS) inhibitors, are exceptionally effective in controlling weeds in agricultural settings. To overcome metabolic resistance caused by the 5-demethylation of pyroxsulam, we sought to replace its 5-methoxy group on the triazolopyrimidine ring with alkyl substituents. This led to the synthesis of a series of N-(7-oxo-4,7-dihydro-[1,2,4]triazolo[1,5-a]pyrimidin-2-yl)arylsulfon-amides, which displayed significant structural diversification potential, culminating in the identification of the herbicidal hit compound I-20. However, the suboptimal lipophilicity compromised its herbicidal efficacy. To rectify this limitation, we modified the 7-carbonyl group to a tert-butoxy group, resulting in the highly active compound I-29. This compound demonstrated herbicidal activity comparable to or exceeding that of penoxsulam against various tested weeds, establishing it as a promising new lead compound and a candidate herbicide for further investigation. Subsequent studies revealed that I-29 exhibited a receptor binding mode and herbicidal activity profiles that closely aligned with those of penoxsulam. Moreover, its spatial structure was found to be even more conducive to inhibiting flavin adenine dinucleotide (FAD)-mediated AHAS activity. This research not only sheds light on addressing the challenge of 5-demethylation metabolic resistance in triazolopyrimidine sulfonamide herbicides but also offers new avenues for the development of AHAS-inhibiting triazolopyrimidine sulfonamide herbicides.

Pyrethroids continue to play a vital role as pesticides for the management of agricultural and public health pests. Despite decades of application, their benefits still highlight substantial potential for further development, although addressing key concerns remains a complex challenge. This article presents a straightforward synthesis of four novel series of pyrethroids that incorporate pyridine heterocycles. These compounds leverage aryloxypyridinyl ethanone scaffolds, which were previously developed by our research group and serve as plug-in molecules. Notably, compound 4-1 exhibited remarkable activity against both mosquitoes and aphids, designating it as a promising lead compound for further exploration of species selectivity. Our findings indicate that substituting the α-cyano group in the benzyl alcohol moiety with a methyl group significantly influences pyrethroid activity. While this substitution typically results in reduced activity, the introduction of a pyridyl group effectively mitigates this decline. Interestingly, this structural modification appears to be essential for enhancing species selectivity. Additionally, optimizing the synergistic interaction between chrysanthemic acid and chrysanthemic alcohol moieties represents another critical strategy for advancing novel pyrethroid development. Our research also reinforces two established principles of structure-activity relationships: (1) a phenoxy group positioned at the meta-position on the pyridine ring enhances activity, and (2) substituents on the benzene ring exert no significant effect on activity. Molecular docking studies provide detailed structural insights that corroborate these conclusions at the receptor level.

Sodium channels play a crucial role in insect neuronal cell activity, and inhibitors targeting insect sodium channels are considered a promising insecticidal strategy. In this study, we designed and synthesized a series of 5-chloro-Indane derivatives containing guanidine targeting insect sodium channels, among which compounds 9f, 9n, and 9o showed good insecticidal activity against the Plutella xylostella, Spodoptera exigua, Spodoptera litura, and Mythimnaseparata walker. The inhibition rate of sodium current of compounds 9f, 9n, and 9o with better insecticidal activity was determined by electrophysiological experiments, and the mechanism of action of compound 9f affecting the growth and development of insects was further analyzed by combining with transcriptomics. In addition, the binding modes and interactions between the compounds and sodium channels were explored by molecular docking and molecular dynamics simulations. This study provides a promising strategy for the development of novel insect sodium channel inhibitors as potential pest control agents.

Designing 16,17-dihydro gibberellin A5-13-acetate (DHGA₅) derivatives based on GA3β-hydroxylase (GA3ox) structural features represents an ideal strategy for developing novel plant growth retardants. Building upon our previous findings, we designed and synthesized a series of carboxyl-protected DHGA₅ derivatives bearing thiosemicarbazone and 1,3,4-thiadiazole moieties. Following photolytic deprotection, compounds 10e and 11l emerged as the most active compounds in their respective series. Notably, compound 10e exhibited superior activity (IC₅₀ = 90 μM) compared to DHGA₅ (IC₅₀ = 97 μM) in Arabidopsis root growth inhibition and exhibited enhanced activity in suppressing the elongation of rice second leaf sheath. The computational simulation results indicated that deprotected compound 10e enhanced binding to OsGA3ox2 through interactions with additional amino acid residues. Interestingly, derivatives showed unexpected potential in alleviating oxidative damage caused by salt stress. This study presents a promising strategy for the development of novel gibberellin biosynthesis inhibitors as potential plant growth retardants.

Light-dependent protochlorophyllide oxidoreductase (LPOR, E.C.1.3.1.33) plays a crucial role in the biosynthesis of chlorophyll in plants. Therefore, inactivating LPOR can hinder the production of chlorophyll to achieve the effect of weed control. In this research, utilizing an active substructure splicing method, 20 new 1,2,4-oxadiazole compounds targeting LPOR were synthesized. Among them, compounds 5j, 5k and 5q exhibited superior inhibitory efficacy in greenhouse herbicidal trials. In vitro enzyme activity assays indicated that 5q significantly inhibited Arabidopsis thaliana LPOR (AtLPOR), with an IC₅₀ value of 17.63 μM. Furthermore, compound 5q exhibited superior crop safety and holds potential application prospects for weed management in cotton. Molecular docking and dynamic simulations were employed to elucidate the binding mode and molecular mechanism of 5q with AtLPOR. These experimental and theoretical results indicate that 5q is a promising candidate for the development of novel herbicides targeting LPOR.

This study presents a phosphine-catalyzed [3 + 2] annulation of sulfamidate imine-derived 1-azadienes with Morita-Baylis-Hillman (MBH) carbonates or allenoates, affording densely functionalized spiro[oxathiazole-cyclopentene] architectures under mild reaction conditions in generally high yields and excellent diastereoselectivities. Through a reductive ring contraction sequence of the spirocyclic thiosulfamide, valuable spirocyclic aziridine derivatives were accessed conveniently via both two-step and one-pot protocols.