Studies toward understanding the SAR around the sulfoximine moiety of the sap-feeding insecticide sulfoxaflor.

BACKGROUND: The discovery of sulfoxaflor (Isoclast™ active) stemmed from a novel scaffold-based approach toward identifying bioactive molecules. It exhibits broad-spectrum control of many sap-feeding insect pests, including aphids, whiteflies, hoppers and Lygus. Systematic modifications of the substituents flanking each side of the sulfoximine moiety were carried out to determine whether these changes would improve potency. RESULTS: Structure-activity relationship (SAR) studies showed that, with respect to the methylene linker, both mono- and disubstitution with alkyl groups of varying sizes as well as cyclic analogs exhibited excellent control of cotton aphids. However, against green peach aphids a decrease in activity was observed with substituents larger than ethyl as well as larger cycloalkyl groups. At the terminal tail there appeared to be a narrow steric tolerance as well, with linear groups or small rings more active against green peach aphids than bulkier groups. CONCLUSION: A novel series of compounds exploring the substituents flanking the sulfoximine moiety of sulfoxaflor were prepared and tested for bioactivity against cotton aphids and green peach aphids. SAR studies indicated that a decrease in green peach aphid potency was observed at the methylene linker as well as at the terminal tail with bulkier substituents. A quantitative structure-activity relationship analysis of the compounds revealed significant correlation of activity with two molecular descriptors, vol (volume of a molecule) and GCUT_SMR_3 (molar refractivity). This predictive model helps to explain the observed activity with the various substituents. © 2016 Society of Chemical Industry.

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.

Solid-phase total synthesis and structure proof of callipeltin B.

The cytotoxic, cyclic heptadepsipeptide, natural product callipeltin B was synthesized on a solid-phase support in 15% overall yield. Comparison of the 1H NMR spectra of three synthetic isomers with those of callipeltin B confirmed the configurational reassignment of its threonine residues as d-allothreonine and the assignment of the configuration of its beta-methoxytyrosine residue as (2R,3R).