Design, Synthesis, Fungicidal Activity, and Unexpected Docking Model of the First Chiral Boscalid Analogues Containing Oxazolines

作者：Shengkun Li, Dangdang Li, Taifeng Xiao, Shasha Zhang, Zehua Song, Hongyu Ma · 发表于：Journal of Agricultural and Food Chemistry · 年份：2016 · DOI：10.1021/acs.jafc.6b03464 · 被引用次数：101 · 研究领域：Fungal Plant Pathogen Control、Synthesis and Biological Evaluation、Synthesis and biological activity

Chirality greatly influences the biological and pharmacological properties of a pesticide and will contribute to unnecessary environmental loading and undesired ecological impact. No structure and activity relationship (SAR) of enantiopure succinate dehydrogenase inhibitors (SDHIs) was documented during the structure optimization of boscalids. On the basis of commercial SDHIs, oxazoline natural products, and versatile oxazoline ligands in organic synthesis, the first effort was devoted to explore the chiral SDHIs and the preliminary mechanism thereof. Fine-tuning furnished chiral nicotinamides 4ag as a more promising fungicidal candidate against Rhizoctonia solani, Botrytis cinerea, and Sclerotinia sclerotiorum, with EC 50 values of 0.58, 0.42, and 2.10 mg/L, respectively. In vivo bioassay and molecular docking were investigated to explore the potential in practical application and plausible novelty in action mechanism, respectively. The unexpected molecular docking model showed the different chiral effects on the binding site with the amino acid residues. This chiral nicotinamide also featured easy synthesis and cost-efficacy. It will provide a powerful complement to the commercial SDHI fungicides with the introduction of chirality.