Synthesis and herbicidal activity of spiro 3‐Acyltetramic acid derivatives as endogenous abscisic acid synthesis regulator and HPPD inhibitors

Abstract BACKGROUND Potent herbicidal activity of tetramic acid containing compounds call for studying the structure–activity relationship of its derivatives. RESULTS A series of novel 3‐acyl‐5‐spiro tetramic acid derivatives ( C1–C12 , L1–L18 ) were synthesized and evaluated for their herbicidal activities. Herbicidal activity tests showed most compounds exhibited >50% inhibition rate against Portulaca oleracea and a certain inhibitory activity against Echinochloa crusgalli , comparable to the commercial 2,4‐D. Most L1–L18 compounds had good control efficiencies against Chenopodium album under pre‐emergence treatment at 500 g ha −1 ; L2 and L3 also exerted outstanding postemergence herbicidal activity against C. album , with control rates equivalent to mesotrione. L2 reduced chlorophyll and carotenoid contents in C. album and regulated the synthesis of endogenous abscisic acid. Molecular docking and molecular dynamics simulations further verified the stability of the complex formed by compound L2 and At HPPD. CONCLUSION The mode‐of‐action and herbicidal activity indicate that L2 is a potential lead compound for further development of novel natural product derived HPPD herbicides. © 2026 Society of Chemical Industry.