Synthesis, Fungicidal Activity, and Mechanism of Action of Pyrazole Amide and Ester Derivatives Based on Natural Products l-Serine and Waltherione Alkaloids.

Abstract

The development of new green fungicides based on the structural optimization of natural products can effectively solve the problems of low safety and high pathogen resistance of traditional fungicides. In this paper, based on pyrazole amide compound h-I-9 with excellent fungicidal activity discovered in the previous work, a series of l-serine-derived pyrazole amide and waltherione alkaloid-derived pyrazole ester derivatives were synthesized. The structures were successively identified by 1H NMR, 13C NMR, high-resolution mass spectrometry, and X-ray single-crystal diffraction. The in vitro and in vivo fungicidal activity screening demonstrated that compound II-5 showed a good inhibition rate against Physalospora piricola. A transmission electron microscope and fluorescence microscope observation further revealed that compound II-5 may cause damage to the cell membranes and vacuoles, and the hyphae treated with II-5 could produce obvious and easily observed blue fluorescence. The succinate dehydrogenase (SDH) enzymatic activity and molecular docking simulation indicated that compounds I-3 and I-4 may be potential SDH inhibitors against Alternaria sp.