Expanding the structure-activity relationship of sulfoxaflor: the synthesis and biological activity of N-heterocyclic sulfoximines.

BACKGROUND: Sulfoxaflor, a new insect control agent developed by Dow AgroSciences, exhibits broad-spectrum control of many sap-feeding insect pests, including aphids, whiteflies, leafhoppers, planthoppers and lygus bugs. During the development of sulfoxaflor, structure-activity relationship (SAR) exploration of the sulfoximine functional group revealed that the nature of the sulfoximine nitrogen substituent significantly affects insecticidal acitivity. As part of the investigation to probe the various electronic, steric and lipophilic parameters at this position, a series of N-heterocyclic sulfoximines were synthesized and tested for bioactivity against green peach aphid. RESULTS: Using a variety of chemistries, the nitrile substituent was replaced with different substituted five- and six-membered heterocycles. The compounds in the series were then tested for insecticidal acitivty against green peach aphid in foliar spray assays. In spite of the larger steric demand of these substituents, the resulting N-heterocyclic sulfoximine analogs displayed good levels of efficacy. In particular, the N-thiazolyl sulfoximines exhibited the greatest activity, with LC50 values as low as 1 ppm. CONCLUSIONS: The novel series of N-heterocyclic sulfoximines helped to advance the current knowledge of the sulfoxaflor SAR, and demonstrated that the structural requirement for the sulfoximine nitrogen position was not limited to small, electron-deficient moeities, but rather was tolerant of larger functionality.

Sulfoxaflor and the sulfoximine insecticides: chemistry, mode of action and basis for efficacy on resistant insects.

The sulfoximines, as exemplified by sulfoxaflor ([N-[methyloxido[1-[6-(trifluoromethyl)-3-pyridinyl]ethyl]-λ(4)-sulfanylidene] cyanamide] represent a new class of insecticides. Sulfoxaflor exhibits a high degree of efficacy against a wide range of sap-feeding insects, including those resistant to neonicotinoids and other insecticides. Sulfoxaflor is an agonist at insect nicotinic acetylcholine receptors (nAChRs) and functions in a manner distinct from other insecticides acting at nAChRs. The sulfoximines also exhibit structure activity relationships (SAR) that are different from other nAChR agonists such as the neonicotinoids. This review summarizes the sulfoximine SAR, mode of action and the biochemistry underlying the observed efficacy on resistant insect pests, with a particular focus on sulfoxaflor.