Pesticides avermectins

The avermectins are closely related to another group of pesticidal natural products, the milhemycins. First described by Japanese workers, milhemycins were later found to be more abundant in nature than the avermectins (7—12). Both the avermectins and milhemycins are sixteen-memhered lactones, with a spiroketal system containing two six-memhered rings. The principal difference between them is that the avermectins have an a-L-oleandrosyl-a-L-oleandrosyl disaccharide attached at the 13-position whereas the milhemycins have no 13-substituent. Milhemycin stmctures are shown in Figure 2. 

The avermectins, a family of compounds with potent anthelmintic, insecticidal and acaricidal activity, have vividly demonstrated that fermentation products can have entirely unanticipated activities. Besides their utility in animals, they show great promise for the control of insect pests of plants. Although antibiotics have found only a limited role in the control of plant diseases, the desire to find environmentally acceptable alternatives to the chemicals currently used has prompted new research efforts to discover fermentation products for use as pesticides. 

The microorganism was classified as a new species of actinomycete. Streptomyces avermitilis. Its anthelmintic activity was shown to reside in 8 closely related macrocyclic lactones, named avermectins, which were also found to possess activity against free-living and parasitic arthropods. One of the natural components, avermectin is now being evaluated as a pesticide for the control of mites of citrus and cotton crops and control of the Red Imported Fire Ant. A chemical derivative, 22,23-dihydroavermectin or ivermectin, has been developed as an antiparasitic agent. It is being marketed for use in cattle, horses and sheep and is expected to become available for swine and dogs. 

The title of this session. Guided and Serendipitous Discovery (within the symposium. Approaches to Rational Synthesis of Pesticides) focuses attention on the nature of the discovery, rather than the outcome. The discovery of the avermectin family of compounds was by no means serendipitous those who were seeking found what they sought. It is the purpose of this paper to record the manner of the seeking and the manner... 

The avermectin natural products are pesticides possessing novel chemistry and mode of action. Cross-resistance has not been observed in laboratory or field studies with mites andinsects tolerant to commercially available organophosphate, carbamate, chlorinated hydrocarbon and pyrethroid pesticides. 

Onchocerciasis -ivermectin treatment [ANTIPARASITIC AGENTS - AVERMECTINS] (Vol 3) -pesticide control of [PESTICIDES] (Vol 18)... 

Anthelmintic agents are a smaller, less diverse group than antimicrobial agents. They include levamisole and the benzimidazoles, and the newer avermectins. The benzimidazoles include thiabendazole which has also been used as a pesticide on plants and as a food preservative. Chemical methods have been used widely to quantify the residues of these substances in food, as part of national control programmes. They are an important sub-group of the antiparasitic agents that many consider to be essential for good animal husbandry. 

Synthetic pyrethroids, avermectins, juvenile hormone mimics, biological pesticides 1985- Genetically engineered organisms... 

Avermectins and milbemycins are naturally occurring 16-membered macrolactones that show a broad spectrum of anthelmintic and pesticidal activity with relatively low toxicity to both humans and animals. The milbemycins differ from the avermectins primarily in the lack of a disaccharide moiety and oxygen functionality at Cl3,... 

One of these pairs, avermectin Bi, i.e., the mixture of avermectins Bia (>80%) and Bib (<20%), is commonly referred to as abamectin (Fig. 29.6.2). It was foimd to be active against nematodes [8, 9], insects [10-12], and mites [13]. Subsequently, abamectin was selected for development in crop protection, and it was introduced to the market-place as an agricultural pesticide against a broad spectrum of phytophagous mites and insects in 1985. Merck scientists performed a... 

First structure-activity relationships relating to crop protection targets were reported by Fisher in 1984 [47]. This study showed that avermectin Bia was somewhat more active then mUbemydn D against Tetranychus urticae, Hdiothis virescens, and Mdoidogyne incognita. As milbemycin D can be viewed as the 22,23-dihydro-13-desoxy derivative of avermectin Bib, this comparison reflects the influence of the disaccharide portion of avermectins on their activity as pesticides. 

The Pesticide Manual A World Compendium, 13 edition, C. D. S. Tomlin (Ed.), British Crop Protection Council, 2003. 2 M. J. Turner, J. M. Schaeffer, Mode of Action of Ivermectin, in Ivermectin and Abamectin, W. C. Campbell (Ed.), Springer, New York, Berlin, Heidelberg, pp. 73-88,1989. 3 J. P. Arena, Parasitol. Today, 1994, 10, 35-37. 4 S. P. Rohrer, J. P. Arena, Molecular Action of Insecticides on Ion Channels, ACS Symposium Series No 591, American Chemical Society, Washington DC, pp. 264-283,1995. 5 R. K. Jansson, R. A. Dybas, Avermectins Biochemical Mode of Action, Biological Activity and Agricultural Importance, in Insecticides with Novel Modes of Action Mechanisms and Application,... 

In the middle of the 20th century, the synthetic development of DDT and other chlorinated hydrocarbons (C.H.), increased insecticidal activity well beyond that of most natural products. Problems arose with bioaccumulation of C.H. residues in the food chain, human fat tissue, mother s milk, as well as the development of insecticide resistance. It became obvious there were limitations to synthetic technology as well. The modification of a natural product, for example, from chrysanthemum flowers and their pyrethrum extracts (7) to pyrethroids such as allethrin, resmethrin, permethrin (2), and deltamethrin created a model in which insecticides are created from the skeleton of insecticidally active natural molecules. Thus, the avermectin, abamectin, ivermectin family of pesticides originated from compounds produced by the soil bacterium, Streptomyces avermitilis (5), and the commercially successful chloronicotinyl insecticides, though not derived from nicotine, are chemically related 4). Both pyrethroids and chloronicotinyls are currently used commercially as termiticides. We have previously provided a detailed review of natural products as pesticidal agents for control of the Formosan subterranean termites, Coptotermes formosanus Shiraki (5). 

Avermectins their chemistry and pesticidal activity, R. A. Dybas and A. St. J. Green, Proc. Br. Crop Prot. Conf. Pests Dis, 1984, 3, 947. 

Natural products provide leads for the synthesis of pesticides with desirable properties. Often, from an economic stanc int, only synthesis will provide adequate quantities to justify the development of a product. There are a few exairples of identificatioi of a natural product that has led to a marketable product. Th incl ]de the pyrethroids, eizadirachtin, the 3 -roethoxyacrylate fungicides, insect pheromones and hormones, and the avermectins. 

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