Synthesis of Epoxyoxirenes: Phytotoxic Activity and Enzymatic Target Identification

Chemical control is key to minimizing agricultural losses, driving the search for more efficient and selective herbicides. This study reports the synthesis of epoxyoxirenes, their phytotoxic evaluation, and an in silico analysis to identify the protein target of the most active compound in plants. Compounds 2-19 were tested on Lactuca sativa spp., Allium cepa spp., Cucumis sativus spp., Triticum aestivum, and Bidens pilosa. The synthetic route began with anhydride 1, obtained via a Diels-Alder reaction between maleic anhydride and furan (91% yield). Anhydride 1 was converted into amides 2-7 through reactions with aromatic amines (>92% yields), followed by cyclization to imides 8-13 (60-83% yields), and subsequent epoxidation to afford epoxides 14-19 (62-98% yields). All the compounds interfered with seedling development, with compounds 2-7 showing the greatest phytotoxicity to B. pilosa at concentrations of 500 μM and 1000 μM. An in silico analysis suggested plant tubulin as a potential protein target for the most active compounds. These findings highlight epoxyoxirenes as promising scaffolds for novel herbicide development and support further investigation into their mechanism of action.