Design, Synthesis, and Metabolism Studies of Triketone-Type Proherbicides for Weed Control in Rice Fields.

4-Hydroxyphenylpyruvate dioxygenase (HPPD, EC 1.13.11.27) is a critical enzyme for green herbicide discovery. This study aimed to develop new HPPD inhibitors for the efficient control of Echinochloa crus-galli in rice fields. A series of 41 triketone derivatives were designed and synthesized using structure-based and proherbicide strategies. The herbicidal activity of the newly synthesized compounds was evaluated against common weeds in rice fields, including E. crus-galli and Leptochloa chinensis. Among them, 2-(2-chloro-4-(methylsulfonyl)-3-((2,2,2-trifluoroethoxy)methyl)benzoyl)-3-((5-methoxy-1H-benzo[d]imidazol-2-yl)thio)cyclohex-2-en-1-one, compound IIy, showing high efficiency against E. crus-galli and L. chinensis, including the resistant biotypes at dosages as low as 19.62-33.26 g of ai/ha, which were significantly more active than that of bicyclopyrone. The density functional theory calculations and metabolism studies revealed the action mechanisms of IIy. The field trials showed that IIy could effectively control the weeds in rice fields at 90-150 g of ai/ha by postemergence application. Our findings suggested the great potential of IIy to be developed as a highly effective herbicide for weed management in paddy fields.