Design, Synthesis and Bioactivity of Benzyl Propiolates with Broad-Spectrum Inhibition Activity on Phytopathogenic Fungi.

As part of our continuing research on propiolic acid derivatives, a series of benzyl propiolate derivatives and analogues were designed, synthesized, and investigated for inhibition activity and on phytopathogenic fungi, structure-activity relationship (SAR) and action mechanism. The results showed that most of the compounds had potent and broad-spectrum antifungal activity at 50 μg/mL. Among the compounds, 2-bromobenzyl propiolate () displayed the highest comprehensive activity with total activity index (TAI) of 4.57 against all the eight test fungi followed by 3-fluorobenzyl propiolate () (TAI = 4.53), superior to positive fungicides thiabendazole (TAI < 4.12) and/or azoxystrobin (TAI < 2.90). Relative to the other fungi, and revealed higher total susceptibility indexes (TSI) of 11.1 and 8.98, respectively, for all compounds. and (4-chlorobenzyl propiolate) gave the smallest EC values of 0.86 and 0.67 μg/mL against and , respectively, superior or comparable with thiabendazole and azoxystrobin. As a representative, at 200 μg/mL displayed 100% protection on infections on potatoes over 7 days and high safety for plant growth. In antifungal mechanism, was able to change mycelial morphology, destroy the structures of both hypha and cell membrane, increase the intracellular ROS level, decrease the intracellular mitochondrial membrane potential level, and change the permeability of the cell membrane. The SAR showed that ethynyl is a key group for the activity, and the presence of halogen atoms at the 2-site of the benzene ring can significantly improve the activity in most cases. Thus, benzyl propiolate can be considered a novel antifungal lead compound, while can be considered a promising fungicide candidate to develop new agricultural fungicides.