The discovery of sulfoxaflor [N-[methyloxido[1-[6-(trifluoromethyl)-3-pyridinyl]ethyl]-λ(4)-sulfanylidene] cyanamide] resulted from an investigation of the sulfoximine functional group as a novel bioactive scaffold for insecticidal activity and a subsequent extensive structure-activity relationship study. Sulfoxaflor, the first product from this new class (the sulfoximines) of insect control agents, exhibits broad-spectrum efficacy against many sap-feeding insect pests, including aphids, whiteflies, hoppers, and Lygus, with levels of activity that are comparable to those of other classes of insecticides targeting sap-feeding insects, including the neonicotinoids. However, no cross-resistance has been observed between sulfoxaflor and neonicotinoids such as imidacloprid, apparently the result of differences in susceptibility to oxidative metabolism. Available data are consistent with sulfoxaflor acting via the insect nicotinic receptor in a complex manner. These observations reflect the unique structure of the sulfoximines compared with neonicotinoids.

Natural products (NPs) have long been used as pesticides and have broadly served as a source of inspiration for a great many commercial synthetic organic fungicides, herbicides and insecticides that are in the market today. In light of the continuing need for new tools to address an ever-changing array of fungal, weed and insect pests, NPs continue to be a source of models and templates for the development of new pest control agents. Interestingly, an examination of the literature suggests that NP models exist for many of the pest control agents that were discovered by other means, suggesting that, had circumstances been different, these NPs could have served as inspiration for the discovery of a great many more of today's pest control agents. Here, an attempt is made to answer questions regarding the existence of an NP model for existing classes of pesticides and what is needed for the discovery of new NPs and NP models for pest control agents.

A method to rapidly identify acetolactate synthase/acetohydroxyacid synthase (ALS/AHAS)-resistant weeds is described based upon the differential accumulation of acetoin in the presence and absence of an ALS/AHAS inhibitor herbicide. Acetoin accumulation is induced by inhibition of ketol-acid reductoisomerase (KARI), the enzyme immediately following ALS/AHAS in the biosynthesis of branched-chain amino acids. Inhibition of ALS/AHAS prevents the build up of acetoin and forms the basis for distinguishing between sensitive and resistant biotypes. A new inhibitor of KARI, 1,1-cyclopropanedicarboxylic acid (CPCA), is described and was found to cause acetoin accumulation in velvetleaf leaf disks over the concentration range of 2 to 100 000 μM. In the presence of CPCA, a number of species important to monitor for ALS/AHAS resistance were found to accumulate acetoin at rates sufficient for resistance diagnosis in 2 to 8 h. In velvetleaf, the youngest apical leaf was found to be the most active in acetoin accumulation. The resistance diagnosis method was validated by clearly distinguishing between imazaquin-sensitive and imazaquin-resistant cocklebur biotypes.

Field isolates of Phoma macrostoma were obtained from diseased Canada thistle growing in several geographically diverse regions. Bleaching and chlorotic symptoms were present on the infected plants. The isolates grown in liquid culture were found to produce phytotoxic metabolites which also caused bleaching when applied foliarly to several broadleaf species. Bioassay-directed isolation led to the discovery of macrocidins A and B, the first representatives of a new family of cyclic tetramic acids. This new chemotype may offer significant potential as a template for herbicide design.

The substituted 1,2,4-triazolo[ 1,5-a]pyrimidines are a new class of highly active herbicides. Protection of Arabidopsis thaliana seedlings fiom triazolopyrimidine-induced injury by the branched-chain amino acids was observed. Acetolactate synthase (EC 4.1.3.18) was isolated and found to be quite sensitive to inhibition. I,, values for inhibition of the enzyme fiom a number of plant sources show little variation and no correlation to wholeplant response, suggesting uptake, translocation and metabolism play key roles in modulating herbicidal activity. Further studies indicate that these chemicals are slow, tight-binding inhibitors that are readily dissociated by gel filtration. Some correlations between in-vitro activity and in-vivo activity were observed for ortho-substituted analogs on selected broadleaf species.