Fragments recombination, design, synthesis, safener activity and CoMFA model of novel substituted dichloroacetylphenyl sulfonamide derivatives

Abstract

BACKGROUND Isoxaflutole (IXF), as a kind of 4‐hydroxyphenylpyruvate dioxygenase (HPPD) inhibitor, has been widely used in many kinds of plants. IXF can cause injury in corn including leaf and stem bleaching, plant height reduction or stunting, and reduced crop stand. Safeners are co‐applied with herbicides to protect crops without compromising weed control efficacy. With the ultimate goal of addressing Zea mays injury caused by IXF, a series of novel substituted dichloroacetylphenyl sulfonamide derivatives was designed on the basis of scaffold hopping and active substructure splicing. RESULTS A total of 35 compounds were synthesized via acylation reactions. All the compounds were characterized by infrared (IR), proton and carbon‐13 nuclear magnetic resonance (1H‐NMR and 13C‐NMR), and high‐resolution mass spectrometry (HRMS). The configuration of compound II‐1 was confirmed by single crystal X‐ray diffraction. The bioassay results showed that all the title compounds displayed remarkable protection against IXF via improved content of carotenoid. Especially compound II‐1 which possessed better glutathione transferases (GSTs) activity and carotenoid content than the contrast safener cyprosulfamide (CSA). All the satisfied parameters suggested that the Comparative Molecular Field Analysis (CoMFA) model was reliable and stable [with a cross‐validated coefficient (q2) = 0.527, r2 = 0.995, r2 pred = 0.931]. The molecular docking simulation indicated that the compound II‐1 and CSA could compete with diketonitrile (DKN) at the active site of HPPD, which is a hydrolyzed product of IXF in plants, causing the herbicide to be ineffective. CONCLUSIONS The present work revealed that the compound II‐1 deserves further attention as the candidate structure of safeners. © 2020 Society of Chemical Industry

Fragmenlt Recombination Design, Synthesis, and Safener Activity of Novel Ester-Substituted Pyrazole Derivatives

“…It is a highly selective stem and leaf treatment agent. , However, due to the long-term and widespread use of FE, crops suffer varying degrees of phytotoxicity. − The application of FE results in crop yellowing, crop growth inhibition, and even crop death in serious cases. To reduce damage to crops, many methods have been reported that incorporate the scientific management of crop rotation and cultivation and the research and development of new herbicides. , In addition, the use of herbicide safeners is also considered to be an efficient solution. − …”

Design, Synthesis, and SAR of Novel 1,3-Disubstituted Imidazolidine or Hexahydropyrimidine Derivatives as Herbicide Safeners

“…All known herbicide safeners contain at least one aromatic ring and five or six heterocyclic rings bearing N and O atoms . Bioisosterism and active group combination are the primary methods of developing novel pesticides. − Based on the similarities of their molecular structures, several 1,3-disubstituted imidazolidine or hexahydropyrimidine derivatives were designed and synthesized by bioisosterism and active fragment combination (Scheme ). The parent skeleton heterocyclic 1,3-diazo was obtained by bioisosterism using the commercial safener R-28725 as the lead compound.…”

Design, synthesis, and herbicidal activity of novel phenoxypyridine derivatives containing natural product coumarin

“…Based on these test results, the promising compound IV‐6 was evaluated in the field in 2020 65,66 . The results of the field trials are shown in Table 4.…”