Design and Synthesis of Novel Pyrimidinedione Derivatives Containing Dithioacetal Structures as Safer Protoporphyrinogen IX Oxidase Inhibitors

Protoporphyrinogen IX oxidase (PPO, EC 1.3.3.4) is a hot spot in the research of green herbicide targets and is often used to prepare novel and efficient herbicides. In this work, we integrated the antiviral disulfide acetal moiety into a pyrimidinedione scaffold, leading to the design and synthesis of a series of novel pyrimidinedione derivatives. The results of the postemergence herbicidal activity assay showed that the majority of the synthesized compounds exhibited significant herbicidal efficacy. Notably, compound S1 controls over 80% of various weeds at only 4.7 g a.i./ha. Further PPO activity experiments showed that compound S1 (IC50 = 0.0151 μM) demonstrated superior PPO inhibition over the reference drug saflufenacil (IC50 = 0.0181 μM). Additionally, at a dose of 150 g a.i./ha, compound S1 is safe for both rice and wheat. Therefore, S1 can be considered a lead for the development of efficient and safe PPO inhibitors.