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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.

BACKGROUND: The commercialization of new insecticides is important for ensuring that multiple effective product choices are available. In particular, new insecticides that exhibit high potency and lack insecticidal cross-resistance are particularly useful in insecticide resistance management (IRM) programs. Sulfoxaflor possesses these characteristics and is the first compound under development from the novel sulfoxamine class of insecticides. RESULTS: In the laboratory, sulfoxaflor demonstrated high levels of insecticidal potency against a broad range of sap-feeding insect species. The potency of sulfoxaflor was comparable with that of commercial products, including neonicotinoids, for the control of a wide range of aphids, whiteflies (Homoptera) and true bugs (Heteroptera). Sulfoxaflor performed equally well in the laboratory against both insecticide-susceptible and insecticide-resistant populations of sweetpotato whitefly, Bemisia tabaci Gennadius, and brown planthopper, Nilaparvata lugens (Stal), including populations resistant to the neonicotinoid insecticide imidacloprid. These laboratory efficacy trends were confirmed in field trials from multiple geographies and crops, and in populations of insects with histories of repeated exposure to insecticides. In particular, a sulfoxaflor use rate of 25 g ha−1 against cotton aphid (Aphis gossypii Glover) outperformed acetamiprid (25 g ha−1) and dicrotophos (560 g ha−1). Sulfoxaflor (50 g ha−1) provided a control of sweetpotato whitefly equivalent to that of acetamiprid (75 g ha−1) and imidacloprid (50 g ha−1) and better than that of thiamethoxam (50 g ha−1). CONCLUSION: The novel chemistry of sulfoxaflor, its unique biological spectrum of activity and its lack of cross-resistance highlight the potential of sulfoxaflor as an important new tool for the control of sap-feeding insect pests. Copyright © 2010 Society of Chemical Industry

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.

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. Copyright © 2008 Society of Chemical Industry

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.

Eight triazolopyrimidine sulfonanilides were tested for metabolic stability in a number of crop and weed species. These data, along within vitrodeterminations of activity (I50) against acetolactate synthase, successfully described thein vivoactivity of these compounds in a two-parameter model. Whole plant activity increased with increasing compound stability and decreasing I50(r2=.78, N = 36). The difficulty in obtaining metabolic stability data during a structure optimization program prompted a study with substituent parameters in models ofin vivoactivity. Models describing whole plant activity in jimsonweed were developed using a series of 5-methyl triazolopyrimidine sulfonanilides that differed only in ortho and meta substituents on the aniline ring. The I50term and clogP were most important to jimsonweed activity. Hence,in vitroactivity (I50) may be a useful component of whole plant structure activity models to aid in identification of barriers toin vivoperformance.

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.

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.

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.

The substituted 1,2,4-triazolo[1,5-a]pyrimidines are a new class of highly active herbicides. Protection of Arabidopsis thaliana seedlings from 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. I50 values for inhibition of the enzyme from a number of plant sources show little variation and no correlation to whole-plant 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.

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 approaches and tools for herbicide lead generation and optimization are increasingly sophisticated. Inputs to screens derived from traditional chemistry, natural products, or combinatorial chemistry are tested in vivo against plants, or in vitro against a target enzyme or receptor. In both cases, high throughput capacity is made possible by automated sample handling and data tracking. Specific in vitro targets may be identified and validated by chemical or genetic means. Increasingly, an inhibitor of a target may be designed with the aid of detailed biochemical and computational tools. If the target compound is active, it will be advanced in successive levels of whole plant testing under conditions that increasingly reflect the actual performance needs of the new herbicide. Detailed studies of uptake, translocation, metabolism in the plant, or partitioning in the soil may be used to understand the barriers to activity delivery and guide the optimization effort. Further, activity on nontarget organisms and persistence in the environment are assessed to ensure the lead optimization program is directed toward discovery of products that are safe to the environment and the end user. Although increasingly sophisticated technical tools provide high quality data to help direct decision making, it is the curiosity and initiative of the discovery scientist that is ultimately responsible for a herbicide product breakthrough. Keywords: natural products; combinatorial chemistry; herbicide target sites; high throughput screening; herbicide design; activity delivery; bio-availability; genomics

DE-498 is a member of a new structural class of highly active herbicides, the triazolopyrimidine sulfonanilides, which act by inhibiting acetolactate synthase (EC 4.1.3.18). DE-498 exhibits broad spectrum activity on broad-leafed weed species with selectivity to several major agronomic crops in soil and foliar applications. The toxicological profile of DE-498 to mammals, fish, and wildlife is favorable. The moderate soil half-life and patterns of crop selectivity of DE-498 eliminate the potential for carryover injury to crops grown in corn/soybean/wheat rotations

The activity of adenosine 5′ triphosphate sulfurylase was determined in crabgrass mesophyll cells, bundle sheath strands, and whole leaf extracts. The enzyme was assayed by following molybdate-dependent pyrophosphate release from ATP, 35SO42− incorporation into adenosine 5′ phosphosulfate, and ATP synthesis dependent upon adenosine 5′ phosphosulfate and inorganic pyrophosphate. With all assays, greater than 90% of the activity was found in extracts from bundle sheath strands. The activities in whole leaf extracts were consistently intermediate between the activities of mesophyll and bundle sheath extracts and extract-mixing experiments gave no indication of enzyme activation or inhibition in vitro. Whole leaf activities were several hundred-fold less than concurrent measurements of ribulose 1,5-bisphosphate and phosphoenolpyruvate carboxylase activities, which is interpreted as being consistent with the relative amounts of elemental carbon and sulfur found in higher plants. A hypothesis is presented for the intercellular compartmentation of sulfur assimilation in relationship to NO3− and CO2 assimilation in leaves of C4 plants.

T RADITIONALLY THE PRINCIPLES of vegetation sampling have been introduced to students in field situations. However, bad weather conditions and the need for background in plant systematics frequently prevent beginning students from learning even the most basic concepts of vegetation sampling in the field. In addition, subtle but important concepts, such as the effects of sample plot shape on estimates of dominance or density, are generally not discussed. The problems associated with introducing vegetation sampling in the field have spawned the development of teaching aids that allow these concepts to be introduced in the laboratory. Several such teaching aids are commercially available, but little information on the use and effectiveness of these aids is available. Our article describes a sampling board we have used in an introductory general ecology course that is inexpensive to construct and that effectively illustrates the principles of vegetation sampling.

The relative activities of (R) and (S) enantiomers of the methyl ester of haloxyfop were determined on annual grasses. Samples enriched in the (S) enantiomer were mark- edly less active than the (R) in petri dish evaluations and foliar applications. The pure (S) enantiomer was estimated by regression to be 1000-fold or less active than the (R). The activity of the (S) enantiomer was found to be equivalent to that of the (R) following preemergence applications. Isolation and characterization of haloxyfop from soil treated with the methyl ester of haloxyfop indicated inversion of the (S) enantiomer to the (R) enantiomer within 7 days. Field trials confirmed the differential activity of enantiomers applied postemergence and their equivalence when applied preemergence. These findings indicate that inversion of the (S) enantiomer to the (R) occurs in soil following preemer- gence applications. Nomenclature: Haloxyfop, 2- (4- ((3- chloro- 5 - (trifluoromethyl)- 2 - pyridinyl) oxy) phenoxyl pro

The antagonism of the methyl ester of haloxyfop {2-[4-[[3-chloro-5-(trifluoromethyl)-2-pyridinyl] oxy] phenoxy propanoic acid} by bentazon [3-(1-methylethyl)-(1H)-2,1,3-benzothiadiazin-4(3H)-one-2,2-dioxide] was evaluated through studies of absorption and translocation in yellow foxtail [Setaria lutescens(Weig. ex Stuntz.) Hubb. # SETLU]. Leaf penetration of haloxyfop was reduced 37% in the presence of bentazon. Bentazon had no effect on translocation from the treated leaf. Direct chemical interactions and contact activity by bentazon do not account for the reduced uptake of haloxyfop. Experimental evidence shows the benzothiadiazione structural class of chemistry to be general antagonists of absorption for foliarly applied herbicides.

Chloroplasts isolated from Opuntia polyacantha Haw. (Cactaceae) are capable of noncyclic electron transport and ATP synthesis. Hill reaction rates, measured by O(2) evolution or by ferricyanide reduction, increase with increasing temperature to approximately 40 C. The temperature optimum of NADP reduction is 42 C while the optimum for noncyclic photophosphorylation is 35 C. NADP-linked phosphorylation exhibits a higher coupling ratio (P/e(2)) than ferricyanide-linked photophosphorylation. The temperature optima for photochemical energy production correlate with photosynthetic properties of Crassulacean acid metabolism (CAM) plants and are discussed in relation to the operation of CAM at high tissue temperature.

Opuntia polyacantha was collected from the shortgrass prairie in Colorado. Carbon dioxide and water vapor exchange was monitored in plants pretreated and analyzed under cool temperatures (20/15°C) and warm temperatures (35/15°C). Well watered plants under a 35/15 thermoperiod supported the fixation of atmospheric CO2 during the night, early morning, and late afternoon. Plants under a 20/15 thermoperiod exhibited CO2 uptake only during the afternoon. The fixation of CO2 at night could be stimulated or induced by decreasing the night temperature. Plants from which water was withheld two or four weeks showed a decline in CO2 fixation with the uptake at night exhibiting the greatest sensitivity. Under conditions of water stress the enhancement of CO2 uptake at night by cool night temperatures was largely lost. Plants water stressed for 4 weeks recovered rapidly upon rewatering under warm or cool temperatures. Rates of CO2 fixation were comparable to well watered plants within 24 h. The effects of temperature and water stress on gas exchange are compared to the in situ growth pattern of O. polyacantha and contrasted with the regulation of gas exchange observed in C3 and C4 grasses of the shortgrass prairie.