Research on Crystal Structure and Fungicidal Activity of the Amide Derivatives Based on the Natural Products Sinapic Acid and Mycophenolic Acid

Abstract

Structural optimization based on natural products is an important and effective way to discover new green pesticides. Here, two series of amide derivatives based on sinapic acid and mycophenolic acid were designed in combination with the fungicidal natural product piperlongumine and synthesized by preparing the carboxylic acid into acyl chloride and then reacting with the corresponding aromatic amines, respectively. The resulting structures were successively characterized by 1H NMR, 13 C NMR, and HRMS. The crystal structures of molecules I-4 and II-5 were analyzed for structure validation. The in vitro inhibitory activity indicated that most of the target products exhibited fungicidal activity equivalent to or even better than fluopyram against Physalospora piricola. The in vivo fungicidal activity demonstrated that the compounds I-5 and II-4 displayed almost the same preventative activity as carbendazim and fluopyram at 200 μg mL−1. The TEM observation revealed that the fungicidal activity of the target molecules against Physalospora piricola may be due to the influence on the mitochondria in the cell structure. These results will provide valuable theoretical guidance for developing the new green fungicides.

Discovery of Aryloxy-, Arylthio-, and Arylamino-Containing Acethydrazides as Fungicidal Agents

“…The in vivo preventative activity of the compounds against F. graminearum was performed by referring to the literature . Wheat leaves were sprayed with the Tween-80 aqueous solution containing the acethydrazide compounds (50 μg·mL –1 ).…”

“…The in vivo preventative activity of the compounds against F. graminearum was performed by referring to the literature. 22 Wheat leaves were sprayed with the Tween-80 aqueous solution containing the acethydrazide compounds (50 μg•mL −1 ). After the solvent was evaporated entirely, the fungus cake with a diameter of 5 mm containing F. graminearum was inoculated.…”

Discovery of Fungicidal Hydrazide Lead Compounds Derived from Sinapic Acid and Mycophenolic Acid

“…Natural products (NPs) have attracted extensive attention due to their multitudinous structures, wide bioactivities, and novel targets of action. , At present, the strategy of NPs-based structural modification and derivation has become an important approach in developing and utilizing new fungicides. Sinapic acid is widely distributed in various plants, and mycophenolic acid is found in a strain of penicillium fungus, both of which have been demonstrated to have a wide range of biological activities. , …”

“…Sinapic acid is widely distributed in various plants, and mycophenolic acid is found in a strain of penicillium fungus, both of which have been demonstrated to have a wide range of biological activities. 14,15 In our previous work, the sinapic acid-derived and mycophenolic acid-derived aliphatic amide compounds were prepared and pointed out to exhibit good fungicidal activity against Physalospora piricola (Figure 1). 15 However, compared with the commercial fungicides, the narrow-spectrum and relatively weak inhibitory activity were disadvantageous to the control of agricultural pathogens.…”

“…In our previous work, the sinapic acid-derived and mycophenolic acid-derived aliphatic amide compounds were prepared and pointed out to exhibit good fungicidal activity against Physalospora piricola (Figure ). However, compared with the commercial fungicides, the narrow-spectrum and relatively weak inhibitory activity were disadvantageous to the control of agricultural pathogens. In our other work, the amide, N -sulfonylamide, and hydrazide compounds were designed and synthesized by aromatic ring replacement, substituents modification, and amide bridge optimization with commercial fluopyram as the initial lead structure (Figure ), from which the acethydrazide compounds with excellent and broad-spectrum fungicidal activity were discovered gradually. − Subsequently, the effects of aromatic rings and substituents on the fungicidal activity were investigated to identify the acetyl hydrazine group as the key pharmacophore.…”