Herbicides, Inhibiting 4‐Hydroxyphenylpyruvate Dioxygenase ( HPPD )

Abstract 4‐Hydroxyphenyl pyruvate dioxygenase (HPPD) is a recently identified herbicide target site. There are currently seven known herbicides that inhibit this target; five commercialized: sulcotrione, isoxaflutole, benzofenap, pyrazolynate, and pyrazoxyfen, and two in the process of being commercialized: mesotrione and benzobicyclon. These herbicides can be classed within three families of 4‐benzoyl‐cyclic aryl or heteroaryl compounds: the benzoyl‐isoxazoles, the benzoyl‐cyclohexanediones, and the benzoyl‐hydroxypyrazoles. As enzymes inhibitors, all share or can give rise to a diketone pharmacophore within their structure. All of these herbicides produce characteristic bleaching symptoms in susceptible species due to the consequences of HPPD inhibition. HPPD catalyzes a complex reaction in which the ketoacid of tyrosine, namely, hydroxyphenylpyruvate (HPPA) is oxidized, decarboxylated, and then rearranged to give 2,5‐dihydroxyphenylacetic acid, or homogentisic acid (HGA). HGA is the precursor of plastoquinone and tocopherols, and the former is a cofactor of phytoene desaturase. This enzyme is key in the biosynthesis of carotenoids, inhibition of which leads to the bleaching symptoms due to the reduction of photosynthetic pigment (chlorophylls and carotenoids) and chloroplast development. The structure and available physicochemical data, toxicology and ecotoxicology data, of these bleaching herbicides is presented, together with a more detailed review of each compound.