Design, synthesis and herbicidal activity of new iron chelating motifs for HPPD-inhibitors

HPPD (p-hydroxyphenylpyruvate dioxygenase) is a herbicidal target that all major companies active in plant protection research have worked on intensely in the last decade. Several modern herbicides with this mode of action have been introduced recently, or are currently in development. The activity of all commercialized HPPD-inhibitors is based on a chelating functionality, which binds to the redoxactive iron center in the enzyme. In the course of our research, leading to the new broad spectrum corn herbicide topramezone by BASF, this chelating functionality has been examined thoroughly, and many new chelating motifs have been synthesized. The chelating motif N–O in combination with CO, which is known for its iron-binding potential from many natural siderophores, was especially promising. Examination of several different motifs of this type resulted in the identification of benzoyl-N-hydroxyimidazoles, which inhibited the HPPD-enzyme with potency comparable to the best known systems. Significant herbicidal activity in the greenhouse could also be identified for some of these compounds, but this activity was weaker than for the analogous benzoylpyrazolones of the topramezone-type.

The target activity of herbicidal benzoylpyrazoles, such as the recently introduced topramezone developed by BASF, is based on chelation of the redox-active iron center of the enzyme p-hydroxyphenylpyruvate dioxygenase (HPPD). By replacing the hydroxypyrazole functionality of these compounds with the isosteric N-hydroxyimidazole, a similar or even improved inhibition on the target could be achieved, but with lower activity in the greenhouse.Figure optionsDownload as PowerPoint slide