Natural products for pest control: an analysis of their role, value and future.

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.

Mevalocidin: a novel, phloem mobile phytotoxin from Fusarium DA056446 and Rosellinia DA092917.

A multiyear effort to identify new natural products was built on a hypothesis that both phytotoxins from plant pathogens and antimicrobial compounds might demonstrate herbicidal activity. The discovery of one such compound, mevalocidin, is described in the current report. Mevalocidin was discovered from static cultures of two unrelated fungal isolates designated Rosellinia DA092917 and Fusarium DA056446. The chemical structure was confirmed by independent synthesis. Mevalocidin demonstrated broad spectrum post-emergence activity on grasses and broadleaves and produced a unique set of visual symptoms on treated plants suggesting a novel mode of action. Mevalocidin was rapidly absorbed in a representative grass and broadleaf plant. Translocation occurred from the treated leaf to other plant parts including roots confirming phloem as well as xylem mobility. By 24 hr after application, over 20 % had been redistributed through-out the plant. Mevalocidin is a unique phytotoxin based on its chemistry, with the uncommon attribute of demonstrating both xylem and phloem mobility in grass and broadleaf plants.

Discovery and characterization of sulfoxaflor, a novel insecticide targeting sap-feeding pests.

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.

Albucidin: a novel bleaching herbicide from Streptomyces albus subsp. chlorinus NRRL B-24108.

A novel nucleoside phytotoxin, albucidin (1), was isolated from the culture broth of Streptomyces albus subsp. chlorinus NRRL B-24108 using bioassay directed fractionation. The structure of the new natural product, albucidin, was determined by NMR and MS; however, the compound has been reported earlier in the literature following synthetic modification of oxetanocin. This is the first report of herbicidal activity for compounds of this structural type. Albucidin shows high levels of broad spectrum activity following post-emergence applications as well as moderate levels of pre-emergence activity. Accordingly, albucidin could be an important new lead for herbicide discovery.

Synthesis and characterization of synthetic analogs of cinnacidin, a novel phytotoxin from Nectria sp.

BACKGROUND: The novel natural product cinnacidin was isolated from a fungal fermentation extract of Nectria sp. DA060097. The compound was found to contain a cyclopentalenone ring system with an isoleucine subunit linked through an amide bond. Initial biological characterization of cinnacidin suggested promising herbicidal activity. RESULTS: Two synthetic analogs, (2S,3S)-2-[(3RS,3aSR,6aRS)-3-methoxy-4-oxo-3,3a,4,5,6,6a-hexahydropentalen-1-ylcarbamoyl]-3-methylvaleric acid and benzyl (2S,3S)-2-[(3RS,3aSR,6aRS)-3-methoxy-4-oxo-3,3a,4, 5,6,6a-hexahydropentalen-1-ylcarbamoyl]-3-methylvalerate, were prepared for further characterization, and their herbicidal activities were compared with that of cinnacidin. CONCLUSIONS: The synthetic compounds were highly phytotoxic on a range of weeds. Based on the symptoms in treated plants, the mode of action of these compounds is suggested to be similar to that of coronatine and jasmonic acid. Coronatine was more active against warm-season grasses, while the cinnacidin benzyl ester analog was more effective on cool-season grasses. In a seedling growth bioassay conducted on bentgrass, the cinnacidin analog was equivalent in activity to coronatine.

The macrocidins: novel cyclic tetramic acids with herbicidal activity produced by Phoma macrostoma.

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.