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Emamectin

File:Emamectins.png
Names
Other names 4′′-Deoxy-4′′-epi-methylaminoavermectin B1; Epimethylamino-4′′-deoxyavermectin; MK 243; EMA; GWN 1972
Identifiers
CAS Number	119791-41-2 155569-91-8 (Benzoate)
3D model (JSmol)	Interactive image
ECHA InfoCard	100.217.470
RTECS number	CL1203005
UNII	8C43B81H4W
CompTox Dashboard (EPA)	DTXSID3035052
SMILES C/C((O1C(OC)(O2O(C)(NC)(OC)C2)()(C)O1)()(C)/C=C/C=C(CO3)/(3()(O)C(C)=C4)(O)4C(O5)=O)=C\C6C5C7(C=C(C)((C)CC)()O7)O6
Properties
Chemical formula	C49H75NO13
Molar mass	886.133 g·mol
Appearance	White or faintly yellow powder
Solubility in water	30-50 ppm (pH 7)
Hazards
NFPA 704 (fire diamond)	2 2 0
Except where otherwise noted, data are given for materials in their standard state (at 25 °C , 100 kPa). Y verify (what is  ?) Infobox references

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.

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 compounds 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.

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, 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 and Caligus elongates, preventing maturation to the reproductive stage.

Most recently, 2009, avermectin compounds, including emamectin, proved useful in pharmaceutical applications in treating human dermatological diseases. Emamectin was deemed a suitable means of treatment of the chronic and progressive inflammatory dermatosis known as rosacea. The pathogenesis of rosacea remains relatively unknown.

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.

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-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.

References

1. Kaoukhov et al. Avermectin Compounds and Treatment of Dermatological Disorders in Humans Therewith. U.S. Patent App. Pub. 2009.
2. ^ D.M. Grossman; D. Cox. Method for the Protection of Trees. World Intellectual Property Collection. 2006.
3. S.L. Waddy; V.A. Merritt; M.N. Hamilton-Gibson; D.E. Aiken; L.E. Burridge (2007). "Relationship between dose of emamectin benzoate and molting response of ovigerous American lobsters (Homarus americanus)". Ecotoxicology and Env. Safety. 67 (1): 95–99. doi:10.1016/j.ecoenv.2006.05.002. PMID 16815547.{{cite journal}}: CS1 maint: multiple names: authors list (link)
4. W. Andersch; P. Evans; B. Springer; K. Buggs; J. Riggs; C. R. Chen. Combinations of biological control agents and insecticides or fungicides. World Intellectual Property Collection. 2001.
5. ^ T.H. Yen; J.L. Lin. Acute Poisoning with Emamectin Benzoate. J. of Toxicology 2004, 42, 5, 657-661.
6. ^ McGonigle, Ian; Lummis, Sarah C. R. (2010). "Molecular Characterization of Agonists That Bind to an Insect GABA Receptor". Biochemistry. 49 (13): 2897. doi:10.1021/bi901698c. PMC 2852148. PMID 20180551.
7. Takai, Kazuya; Soejima, Tomoyuki; Suzuki, Toshio; Kawazu, Kazuyoshi (2001). "Development of a water-soluble preparation of emamectin benzoate and its preventative effect against the wilting of pot-grown pine trees inoculated with the pine wood nematode,Bursaphelenchus xylophilus". Pest Management Science. 57 (5): 463. doi:10.1002/ps.301. PMID 11374165.
8. ^ Ikeda, Haruo; Ōmura, Satoshi (1997). "Avermectin Biosynthesis". Chem. Rev. 97: 2591. doi:10.1021/cr960023p.
9. ^ Rodríguez, EM; Medesani, DA; Fingerman, M (2007). "Endocrine disruption in crustaceans due to pollutants: a review". Comparative biochemistry and physiology. Part A, Molecular & integrative physiology. 146 (4): 661–71. doi:10.1016/j.cbpa.2006.04.030. PMID 16753320.
10. Yen, TH; Lin, JL (2004). "Acute poisoning with emamectin benzoate". Journal of toxicology. Clinical toxicology. 42 (5): 657–61. doi:10.1081/CLT-200026968. PMID 15462160.
11. Emamectin Benzoate; Shenghua Group Safety Card, China, 2008 http://www.chembiok.com/Emamectin.htm (accessed on Feb. 21, 2010).
12. Grant, Andrew N (2002). "Medicines for sea lice". Pest Management Science. 58 (6): 521. doi:10.1002/ps.481. PMID 12138618.

• Insecticides