Design, Synthesis, and Structure–Activity Relationship of Novel Aryl-Substituted Formyl Oxazolidine Derivatives as Herbicide Safeners

Abstract

Nicosulfuron is the leading herbicide in the global sulfonylurea (SU) herbicide market; it was jointly developed by DuPont and Ishihara. Recently, the widespread use of nicosulfuron has led to increasingly prominent agricultural production hazards, such as environmental harm and influence on subsequent crops. The use of herbicide safeners can significantly alleviate herbicide injury to protect crop plants and expand the application scope of existing herbicides. A series of novel aryl-substituted formyl oxazolidine derivatives were designed using the active group combination method. Title compounds were synthesized using an efficient one-pot method and characterized by infrared (IR) spectrometry, 1H and 13C nuclear magnetic resonance (NMR), and high-resolution mass spectrometry (HRMS). The chemical structure of compound V-25 was further identified by X-ray single crystallography. The bioactivity assay and structure–activity relationship proved that nicosulfuron phytotoxicity to maize could be reduced by most title compounds. The glutathione S-transferase (GST) activity and acetolactate synthase (ALS) in vivo were determined, and compound V-12 showed inspiring activity comparable to that of the commercial safener isoxadifen-ethyl. The molecular docking model indicated that compound V-12 competed with nicosulfuron for the acetolactate synthase active site and that this is the protective mechanism of safeners. Absorption, distribution, metabolism, excretion, and toxicity (ADMET) predictions demonstrated that compound V-12 exhibited superior pharmacokinetic properties to the commercialized safener isoxadifen-ethyl. The target compound V-12 shows strong herbicide safener activity in maize; thus, it may be a potential candidate compound that can help further protect maize from herbicide damage.

Design, Synthesis, and Biological Evaluation of Novel Purine Derivatives as Herbicide Safeners

“…GST activity IRRs after treatment with compounds III-3 and III-7 at 40 mg/kg were 121.95 and 99.13% respectively, and these compounds showed low RC 30 values of 5.869 and 4.445 mg/kg, respectively, confirming their superiority over mefenpyr-diethyl. These results affirm that compounds III-3 and III-7 exert robust protective effects, enhancing the tolerance of wheat to herbicides by increasing GST activity, consistent with the findings of Ding et al…”

Design, Synthesis, and Bioactivity of Novel 2-(Arylformyl)cyclohexane-1,3-dione Derivatives as HPPD Inhibitors

“…General Synthetic Procedure for Intermediate 3-Oxocyclohex-1en-1-yl Aromatic Estera1−a29. 43,44 Intermediates were obtained by acylation of the aromatic acid chloride with cyclohexanedione. SOCl 2 (30 mmol) and aromatic carboxylic acid (10 mmol) were dissolved in THF (20 mL), DMF (0.3 mL) was added slowly, and the mixture was stirred for 3 h under reflux at 65 °C.…”

Review on the Discovery of Novel Natural Herbicide Safeners

“…Fragment splicing is a significant technique for designing and optimizing novel skeleton structures with target biological activity. ,, Many examples of this technique have been proved, such as the design of the fungicide fluopyram, the safener isoxadifen-ethyl, and other pesticide molecules designed in recent years (Figure ). − Remarkably, the splicing of the natural backbones with the active substructure of commercial safeners has proven to be feasible and effective in the discovery of novel herbicide safeners.…”