Validation of Dihydroorotate Dehydrogenase as a Herbicide Target: Discovery of Tetflupyrolimet

Dihydroorotate dehydrogenase (DHODH), the enzyme that catalyzes the fourth step of de novo pyrimidine biosynthesis, has long been known as a biological target for various end uses. However, validation of DHODH as a herbicide target has only recently been realized with the discovery of the novel chemistry class of 4-arylpyrrolidinone-3-anilides at FMC. Optimization in this area led to the identification of commercial development candidate tetflupyrolimet, the first member of the new Herbicide Resistance Action Committee (HRAC) Group 28. Tetflupyrolimet provides selective control of key grass weeds in rice and will be the first herbicide with a completely novel mode of action to be introduced to the market in over 30 years. This chapter describes the discovery of tetflupyrolimet and the identification of its molecular target.