Emamectin benzoate
Encyclopedia
Emamectin is the 4”-deoxy-4”-methylamino derivative of abamectin
, a 16-membered macrycyclic lactone produced by the fermentation of the soil actinomycete Streptomyces avermitilis.
It is generally prepared at the salt with benzoic acid
, emamectin benzoate, which is a white or faintly yellow powder. Emamectin is widely used in the US and Canada as an insecticide because of its chloride channel activation properties.
Emamectin is derived from avermectin B1, also known as abamectin, a mixture of the natural avermectin B1a and B1b. Emamectin has also shown promising applications in the eradication of fish lice and in fish farming.
termed B1a and B1b which differ on the C-25 side-chain by one methylene (CH2) group. B1a contains a sec-butyl group while Bab has an isopropyl group. Emamectin is a mixture, typically consisting of 10% B1b and 90% B1a.
Avermectin biosynthesis
is classified into three stages: the formation of the polyketide
-derived initial aglycone
, modification of the initial aglycone to produce avermectin aglycones, and glycosylation
of avermectin aglycones to generate avermectins.
Emamectin has been shown to possess a greater ability to reduce the colonization success of engraver beetles and associated wood borers in loblolly pines (Pinus taeda L).6 A 2006 study regarding bolt-injections of four types of pesticides found emamectin to be the greatest reducer against these species with respect to the amount of larval feeding, length, and number of egg galleries.6 Formation of long vertical lesions in the phloem and xylem surrounding emamectin injection points were found indicating some level of tree-toxicity to the emamectin.
A water-soluble preparation of emamectin in polysorbate
, acetone
, and methanol
was shown to prevent the wilting of Japanese black pine trees inoculated with pine-wood nematodes (Bursaphelenchus xylophilus). Previous treatment of B xylophilus infections involved eradicating the local population of Japanese pine sawyers associated with the spread of the nematode.
Emamectin has also been successfully employed by fish farmers in the control of sea lice in Atlantic salmon.
The United Kingdom, Chile, Ireland, Iceland, Finland, the Faroe Islands, Spain, and Norway are currently registered to use emamectin in their fish feed. Removal of the afflicting sea louse represents an increase in the integrity of their salmonid product due to the subsequent reduction of bacterial and viral pathogens possibly carried by the sea lice. Emamectin has shown efficacy against all life-cycle stages of Lepeophtheirus salmonis (Salmon louse
) and Caligus elongatus (Sea louse), preventing maturation to the reproductive stage.
A related dihydroxy avermectin B1 compound, ivermectin, is utilized orally in humans as an acaricide and insecticide for the treatment of strongyloidiasis
and onchocerciasis
. Veterinarians also employ ivermectin in the treatment of heartworms in dogs and other infestations.
The determination of the active-site for avermectins is difficult due to poor solubility and lipophilicity of these compounds.
The compound stimulates the release of GABA from the synapses between nerve cells and while additionally increasing GABA’s affinity for its receptor on the post-junction membrane of muscle cells in insects and arthropods. The stronger binding of GABA increases the cells permeability to chloride ions within the cell due to the hypotonic concentration gradient. Neurotransmission is thereby reduced by subsequent hyperpolarisation and the elimination of signal transduction.
The membrane protein P-glycoprotein
(P-gp) in mammals and fish significantly reduces emamectin's toxicity by acting as an ATP-dependent efflux pump of macrocyclic lactones out of the brain. P-gp’s efflux of structurally unrelated exogenous compounds out of the brain protects vertebrates against the GABA-ergic action of the compound and thus against its neurotoxicity.
Abamectin
Abamectin is a widely used insecticide and anthelmintic.-Chemistry:Abamectin is a mixture of avermectins containing more than 80% avermectin B1a and less than 20% avermectin B1b. These two components, B1a and B1b have very similar biological and toxicological properties...
, a 16-membered macrycyclic lactone produced by the fermentation of the soil actinomycete Streptomyces avermitilis.
It is generally prepared at the salt with benzoic acid
Benzoic acid
Benzoic acid , C7H6O2 , is a colorless crystalline solid and the simplest aromatic carboxylic acid. The name derived from gum benzoin, which was for a long time the only source for benzoic acid. Its salts are used as a food preservative and benzoic acid is an important precursor for the synthesis...
, emamectin benzoate, which is a white or faintly yellow powder. Emamectin is widely used in the US and Canada as an insecticide because of its chloride channel activation properties.
History
Emamectin, produced by the fungus Streptomyces avermitilis, belongs to the avermectin family of compounds all of which exhibit toxicity for nematodes, arthropods, and several other pests. The benzoate salt of emamectin in particular has found widespread use as an insecticide and is approved by the EPA for use in prevention of emerald ash borer in ash trees.Emamectin is derived from avermectin B1, also known as abamectin, a mixture of the natural avermectin B1a and B1b. Emamectin has also shown promising applications in the eradication of fish lice and in fish farming.
Preparation
Emamectin is derived from abamectin by replacement of a epi-amino-methyl (NHCH3) group by a hydroxyl (-OH) group at the 4”-position. Emamectin, like abamectin, is a mixture of two homologue compoundsHomologous series
In chemistry, a homologous series is a series of compounds with a similar general formula, possessing similar chemical properties due to the presence of the same functional group, and showing a gradation in physical properties as a result of increase in molecular size and mass...
termed B1a and B1b which differ on the C-25 side-chain by one methylene (CH2) group. B1a contains a sec-butyl group while Bab has an isopropyl group. Emamectin is a mixture, typically consisting of 10% B1b and 90% B1a.
Avermectin biosynthesis
Biosynthesis
Biosynthesis is an enzyme-catalyzed process in cells of living organisms by which substrates are converted to more complex products. The biosynthesis process often consists of several enzymatic steps in which the product of one step is used as substrate in the following step...
is classified into three stages: the formation of the polyketide
Polyketide
Polyketides are secondary metabolites from bacteria, fungi, plants, and animals. Polyketides are usually biosynthesized through the decarboxylative condensation of malonyl-CoA derived extender units in a similar process to fatty acid synthesis...
-derived initial aglycone
Aglycone
An aglycone is the non-sugar compound remaining after replacement of the glycosyl group from a glycoside by a hydrogen atom. The spelling aglycon is sometimes encountered .Classes of phytochemicals found in the aglycone and glycosides forms :...
, modification of the initial aglycone to produce avermectin aglycones, and glycosylation
Glycosylation
Glycosylation is the reaction in which a carbohydrate, i.e. a glycosyl donor, is attached to a hydroxyl or other functional group of another molecule . In biology glycosylation refers to the enzymatic process that attaches glycans to proteins, lipids, or other organic molecules...
of avermectin aglycones to generate avermectins.
Uses
Emamectin is widely used in controlling lepidopterous pests (order of insects that as larvae are caterpillars and as adults have four broad wings including butterflies, moths, and skippers) in agricultural products in the US, Japan, Canada, and recently Taiwan. The low-application rate of the active ingredient needed (~6 g/acre) and broad-spectrum applicability as an insecticide has gained emamectin significant popularity among farmers.Emamectin has been shown to possess a greater ability to reduce the colonization success of engraver beetles and associated wood borers in loblolly pines (Pinus taeda L).6 A 2006 study regarding bolt-injections of four types of pesticides found emamectin to be the greatest reducer against these species with respect to the amount of larval feeding, length, and number of egg galleries.6 Formation of long vertical lesions in the phloem and xylem surrounding emamectin injection points were found indicating some level of tree-toxicity to the emamectin.
A water-soluble preparation of emamectin in polysorbate
Polysorbate
Polysorbates are a class of emulsifiers used in some pharmaceuticals and food preparation. They are often used in cosmetics to solubilize essential oils into water-based products. Polysorbates are oily liquids derived from PEG-ylated sorbitan esterified with fatty acids...
, acetone
Acetone
Acetone is the organic compound with the formula 2CO, a colorless, mobile, flammable liquid, the simplest example of the ketones.Acetone is miscible with water and serves as an important solvent in its own right, typically as the solvent of choice for cleaning purposes in the laboratory...
, and methanol
Methanol
Methanol, also known as methyl alcohol, wood alcohol, wood naphtha or wood spirits, is a chemical with the formula CH3OH . It is the simplest alcohol, and is a light, volatile, colorless, flammable liquid with a distinctive odor very similar to, but slightly sweeter than, ethanol...
was shown to prevent the wilting of Japanese black pine trees inoculated with pine-wood nematodes (Bursaphelenchus xylophilus). Previous treatment of B xylophilus infections involved eradicating the local population of Japanese pine sawyers associated with the spread of the nematode.
Emamectin has also been successfully employed by fish farmers in the control of sea lice in Atlantic salmon.
The United Kingdom, Chile, Ireland, Iceland, Finland, the Faroe Islands, Spain, and Norway are currently registered to use emamectin in their fish feed. Removal of the afflicting sea louse represents an increase in the integrity of their salmonid product due to the subsequent reduction of bacterial and viral pathogens possibly carried by the sea lice. Emamectin has shown efficacy against all life-cycle stages of Lepeophtheirus salmonis (Salmon louse
Salmon louse
The salmon louse, Lepeophtheirus salmonis, is a species of copepod in the genus Lepeophtheirus.It is a sea louse, a parasite living on salmon. It lives off the mucus, skin and blood of the fish....
) and Caligus elongatus (Sea louse), preventing maturation to the reproductive stage.
A related dihydroxy avermectin B1 compound, ivermectin, is utilized orally in humans as an acaricide and insecticide for the treatment of strongyloidiasis
Strongyloidiasis
Strongyloidiasis is a human parasitic disease caused by the nematode Strongyloides stercoralis, or sometimes S. fülleborni. It can cause a number of symptoms in people, principally skin symptoms, abdominal pain, diarrhea and weight loss...
and onchocerciasis
Onchocerciasis
Onchocerciasis , also known as river blindness and Robles' disease, is a parasitic disease caused by infection by Onchocerca volvulus, a nematode . Onchocerciasis is the world's second-leading infectious cause of blindness. It is not the nematode, but its endosymbiont, Wolbachia pipientis, that...
. Veterinarians also employ ivermectin in the treatment of heartworms in dogs and other infestations.
Structure and properties
Emamectin, like other avermectins, is a hydrophobic 16-membered macrocyclic lactone. Emamectin differs from avermectins B1a and B1b by the presence of a hydroxyl group at the 4”-epimethylamino group rather than the 4”-position. Avermectins are pentacyclic polyketide-derived compounds linked to a disaccharide of the methylated deoxysugar oleandrose.The determination of the active-site for avermectins is difficult due to poor solubility and lipophilicity of these compounds.
Toxicology and metabolism
Emamectin works as a chloride channel activator by binding gamma aminobutyric acid (GABA) receptor and glutamate-gated chloride channels disrupting nerve signals within arthropods.The compound stimulates the release of GABA from the synapses between nerve cells and while additionally increasing GABA’s affinity for its receptor on the post-junction membrane of muscle cells in insects and arthropods. The stronger binding of GABA increases the cells permeability to chloride ions within the cell due to the hypotonic concentration gradient. Neurotransmission is thereby reduced by subsequent hyperpolarisation and the elimination of signal transduction.
The membrane protein P-glycoprotein
P-glycoprotein
P-glycoprotein 1 also known as multidrug resistance protein 1 or ATP-binding cassette sub-family B member 1 or cluster of differentiation 243 is a glycoprotein that in humans is encoded by the ABCB1 gene...
(P-gp) in mammals and fish significantly reduces emamectin's toxicity by acting as an ATP-dependent efflux pump of macrocyclic lactones out of the brain. P-gp’s efflux of structurally unrelated exogenous compounds out of the brain protects vertebrates against the GABA-ergic action of the compound and thus against its neurotoxicity.