ABSTRACT
This paper reviews the discovery of isoxaflutole (IFT), focusing on the chemical and physicochemical properties which contribute to the herbicidal behaviour of this new herbicide. IFT (5-cyclopropyl-1,2-isoxazol-4-yl alpha alpha alpha-trifluoro-2-mesyl-p-tolyl ketone) is a novel herbicide for pre-emergence control of a wide range of important broadleaf and grass weeds in corn and sugarcane. The first benzoyl isoxazole lead was synthesised in 1989 and IFT in 1990, and the herbicidal potential of the latter was identified in 1991. The decision to develop the molecule was taken after two years of field testing in North America. The biochemical target of IFT is 4-hydroxyphenylpyruvate dioxygenase (HPPD), inhibition of which leads to a characteristic bleaching of susceptible species. The inhibitor of HPPD is the diketonitrile derivative of IFT formed from opening of the isoxazole ring. The diketonitrile (DKN) is formed rapidly in plants following root and shoot uptake. The DKN is both xylem and phloem mobile leading to high systemicity. IFT also undergoes conversion to the DKN in the soil. The soil half-life of IFT ranges from 12 h to 3 days under laboratory conditions and is dependent on several factors such as soil type, pH and moisture. The log P of IFT is 2.19 and the water solubility is 6.2 mg litre-1, whereas the corresponding values for the DKN are 0.4 and 326 mg litre-1, respectively. These properties restrict the mobility of IFT, which is retained at the soil surface where it can be taken up by surface-germinating weed seeds. The DKN, which has a laboratory soil half-life of 20-30 days, is more mobile and is taken up by the roots. In addition to influencing the soil behaviour of IFT and DKN, the greater lipophilicity of IFT leads to greater uptake by seed, shoot and root tissues. In both plants and soil, the DKN is converted to the herbicidally inactive benzoic acid. This degradation is more rapid in maize than in susceptible weed species and this contributes to the mechanism of selectivity, together with the greater sowing depth of the crop.
Subject(s)
4-Hydroxyphenylpyruvate Dioxygenase/antagonists & inhibitors , Enzyme Inhibitors/pharmacology , Herbicides/pharmacology , Isoxazoles/pharmacology , Plants/drug effects , Autoradiography , Benzoic Acid/metabolism , Biological Assay , Chromatography, Thin Layer , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/metabolism , Half-Life , Herbicides/chemistry , Herbicides/metabolism , Isoxazoles/chemistry , Isoxazoles/metabolism , Molecular Structure , Pesticide Residues , Plant Roots/metabolism , Plant Shoots/metabolism , Plants/metabolism , Soil/analysis , SolubilityABSTRACT
[figure: see text] The synthesis of ring opening metathesis, polymer-supported Tosmic reagent 1 is described. This reagent was utilized in the conversion of aldehydes to oxazoles in good yields and purities.
Subject(s)
Oxazoles/chemical synthesis , Indicators and Reagents , Models, Molecular , Molecular Conformation , Molecular Structure , Oxazoles/chemistry , Oxazoles/isolation & purification , Structure-Activity RelationshipABSTRACT
1,2,4-Oxadiazoles were synthesized in solution from aromatic amidoximes and acylating agents supported on a ring opening metathesis polymer (ROMPGEL) backbone. High yields and purities of the 1,2,4-oxadiazoles were obtained with minimal purification.
