Design, Synthesis, and Biological Evaluation of 2-(Benzylsulfonyl)-5-(2-Methoxypyridin-4-yl)-1,3,4-Oxadiazole Derivatives as Novel Herbicides

Abstract

To develop herbicides with a novel mechanism of action, a series of 1,3,4-oxadiazolpyridine derivatives were designed and synthesized based on active splicing and structure optimization. These derivatives (5aa-5bd) were characterized by their melting points, 1H and 13C nuclear magnetic resonance spectroscopy, and high-resolution mass spectrometry. The configuration of 5al was determined using single-crystal X-ray diffraction. In addition, 5al displayed excellent herbicidal activity with an EC50 of 4.03 g/hm2 against E. crus-galli and quinclorac-resistant E. crus-galli at a dosage of 75 g/hm2. At a dosage of 375 g/hm2, 5al was safe for application on rice and sorghum and showed low toxicity (>200 μg/g) towards Apis mellifera. After treatment with 5al, the lamellae of the chloroplast grana of barnyard grass leaves were stacked disorderly and arranged loosely, and some thylakoids were broken, as observed by transmission electron microscopy. Transcriptomics analysis of E. crus-galli revealed that 5al affects the defense response, membranes, plasma membranes, and chloroplasts of differentially expressed genes, which alter membrane permeability and energy metabolism, potentially leading to plant death. Thus, we successfully developed a novel molecular scaffold with a new mechanism of action that exhibits herbicidal activity against resistant E. crus-galli. Therefore, further development of lead herbicides based on this scaffold is required.

Keywords: active splicing, herbicidal activity, resistant barnyardgrass, transcriptomics