Azadirachtin

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Azadirachtin
Azadirachtin.png
Azadirachtin model.png
Names
Preferred IUPAC name
Dimethyl (2aR,2a1R,3S,4S,4aR,5S,7aS,8S,10R,10aS)-10-(acetyloxy)-3,5-dihydroxy-4-[(1aR,2S,3aS,6aS,7S,7aS)-6a-hydroxy-7a-methyl-3a,6a,7,7a-tetrahydro-2,7-methanofuro[2,3-b]oxireno[2,3-e]oxepin-1a(2H)-yl]-4-methyl-8-{[(2E)-2-methylbut-2-enoyl]oxy}octahydro-1H,7H-naphtho[1,8-bc:4,4a-c′]difuran-5,10a(8H)-dicarboxylate
Identifiers
3D model (JSmol)
ChEBI
ChemSpider
ECHA InfoCard 100.115.924 OOjs UI icon edit-ltr-progressive.svg
KEGG
PubChem CID
UNII
  • InChI=1S/C35H44O16/c1-8-15(2)24(38)49-18-12-19(48-16(3)36)32(26(39)43-6)13-46-21-22(32)31(18)14-47-34(42,27(40)44-7)25(31)29(4,23(21)37)35-20-11-17(30(35,5)51-35)33(41)9-10-45-28(33)50-20/h8-10,17-23,25,28,37,41-42H,11-14H2,1-7H3/b15-8+/t17-,18+,19-,20+,21-,22-,23-,25+,28+,29-,30+,31+,32+,33+,34+,35+/m1/s1 Yes check.svgY
    Key: FTNJWQUOZFUQQJ-NDAWSKJSSA-N Yes check.svgY
  • O=C(OC)[C@@]1(O)OC[C@]82[C@@H](OC(=O)/C(=C/C)C)C[C@@H](OC(=O)C)[C@@]7(C(=O)OC)CO[C@@H]([C@@H](O)[C@](C)([C@H]12)[C@]64O[C@]6([C@@H]3[C@@]5(O)/C=C\O[C@H]5O[C@H]4C3)C)[C@@H]78
Properties
C35H44O16
Molar mass 720.721 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Yes check.svgY  verify  (what is  Yes check.svgYX mark.svgN ?)

Azadirachtin, a chemical compound belonging to the limonoid group, is a secondary metabolite present in neem seeds. It is a highly oxidized tetranortriterpenoid which boasts a plethora of oxygen-bearing functional groups, including an enol ether, acetal, hemiacetal, tetra-substituted epoxide and a variety of carboxylic esters.

Contents

Chemical synthesis

Azadirachtin has a complex molecular structure; it presents both secondary and tertiary hydroxyl groups and a tetrahydrofuran ether in its molecular structure, alongside 16 stereogenic centres, 7 of which are tetrasubstituted. These characteristics explain the great difficulty encountered when trying to prepare this compound from simple precursors, using methods of synthetic organic chemistry.

Hence, the first total synthesis was published over 22 years after the compound's discovery: this first synthesis was completed by the research group of Steven Ley at the University of Cambridge in 2007. [1] [2] The described synthesis was a relay approach, with the required, heavily functionalized decalin intermediate being made by total synthesis on a small scale, but being derived from the natural product itself for the gram-scale operations required to complete the synthesis.

Occurrence and use

Initially found to be active as a feeding inhibitor towards the desert locust (Schistocerca gregaria), [3] it is now known to affect over 200 species of insects, by acting mainly as an antifeedant and growth disruptor. It was recently found that azadirachtin possesses considerable toxicity towards African cotton leafworm (Spodoptera littoralis), which are resistant to a commonly used biological pesticide, Bacillus thuringiensis . Azadirachtin fulfills many of the criteria needed for a good insecticide. Azadirachtin is biodegradable (it degrades within 100 hours when exposed to light and water) and shows very low toxicity to mammals (the LD50 in rats is > 3,540 mg/kg making it practically non-toxic).

This compound is found in the seeds (0.2 to 0.8 percent by weight) of the neem tree, Azadirachta indica (hence the prefix aza does not imply an aza compound, but refers to the scientific species name). Many more compounds, related to azadirachtin, are present in the seeds as well as in the leaves and the bark of the neem tree which also show strong biological activities among various pest insects [4] [5] Effects of these preparations on beneficial arthropods are generally considered to be minimal [ citation needed ]. Some laboratory and field studies have found neem extracts to be compatible with biological control. Because pure neem oil contains other insecticidal and fungicidal compounds in addition to azadirachtin, it is generally mixed at a rate of 1 US fluid ounce per US gallon (7.8 mL/L) of water when used as a pesticide.

Azadirachtin is the active ingredient in many pesticides including TreeAzin, [6] AzaMax, [7] BioNEEM, [8] AzaGuard, [9] and AzaSol, [10] Terramera Proof [11] and Terramera Cirkil. [12]

Azadirachtin has a synergistic effect with the biocontrol agent Beauveria . [13]

Nimbecidine is a natural product insecticide mix which is mostly azadirachtin, with some other limonoids. [14]

Mechanism of action

Azadirachtin interferes with a wide variety of insect pathways. [15]

Biosynthesis

Azadirachtin is formed via an elaborate biosynthetic pathway, but is believed that the steroid tirucallol is the precursor to the neem triterpenoid secondary metabolites. Tirucallol is formed from two units of farnesyl diphosphate (FPP) to form a C30 triterpene, but then loses three methyl groups to become a C27 steroid. Tirucallol undergoes an allylic isomerization to form butyrospermol, which is then oxidized. The oxidized butyrospermol subsequently rearranges via a Wagner-Meerwein 1,2-methyl shift to form apotirucallol.

Apotirucallol becomes a tetranortriterpenoid when the four terminal carbons from the side chain are cleaved off. The remaining carbons on the side chain cyclize to form a furan ring and the molecule is oxidized further to form azadirone and azadiradione. The third ring is then opened and oxidized to form the C-seco-limonoids such as nimbin, nimbidinin and salannin, which has been esterified with a molecule of tiglic acid, which is derived from L-isoleucine. It is currently proposed that the target molecule is arrived at by biosynthetically converting azadirone into salanin, which is then heavily oxidized and cyclized to reach azadirachtin.

See also

Related Research Articles

<i>Azadirachta indica</i> Species of plant

Azadirachta indica, commonly known as neem, margosa, nimtree or Indian lilac, is a tree in the mahogany family Meliaceae. It is one of two species in the genus Azadirachta. It is native to the Indian subcontinent and to parts of Southeast Asia, but is naturalized and grown around the world in tropical and subtropical areas. Its fruits and seeds are the source of neem oil. Nim is a Hindustani noun derived from Sanskrit nimba (निंब).

<span class="mw-page-title-main">Pesticide</span> Substance used to destroy pests

Pesticides are substances that are used to control pests. They include herbicides, insecticides, nematicides, fungicides, and many others. The most common of these are herbicides, which account for approximately 50% of all pesticide use globally. Most pesticides are used as plant protection products, which in general protect plants from weeds, fungi, or insects. In general, a pesticide is a chemical or biological agent that deters, incapacitates, kills, or otherwise discourages pests. Target pests can include insects, plant pathogens, weeds, molluscs, birds, mammals, fish, nematodes (roundworms), and microbes that destroy property, cause nuisance, or spread disease, or are disease vectors. Along with these benefits, pesticides also have drawbacks, such as potential toxicity to humans and other species.

<span class="mw-page-title-main">Insecticide</span> Pesticide used against insects

Insecticides are pesticides used to kill insects. They include ovicides and larvicides used against insect eggs and larvae, respectively. Insecticides are used in agriculture, medicine, industry and by consumers. Insecticides are claimed to be a major factor behind the increase in the 20th-century's agricultural productivity. Nearly all insecticides have the potential to significantly alter ecosystems; many are toxic to humans and/or animals; some become concentrated as they spread along the food chain.

<span class="mw-page-title-main">Pyrethrin</span> Class of organic chemical compounds with insecticidal properties

The pyrethrins are a class of organic compounds normally derived from Chrysanthemum cinerariifolium that have potent insecticidal activity by targeting the nervous systems of insects. Pyrethrin naturally occurs in chrysanthemum flowers and is often considered an organic insecticide when it is not combined with piperonyl butoxide or other synthetic adjuvants. Their insecticidal and insect-repellent properties have been known and used for thousands of years.

<span class="mw-page-title-main">Limonoid</span> Class of chemical compounds

Limonoids are phytochemicals of the triterpenoid class which are abundant in sweet or sour-scented citrus fruit and other plants of the families Cucurbitaceae, Rutaceae, and Meliaceae. Certain limonoids are antifeedants such as azadirachtin from the neem tree.

The tetranortriterpenoid class of naturally occurring organic compounds, of which the most noted compound is azadirachtin, extracted from the neem tree that displays insecticidal properties. Azadirachtin mimics insect hormones called ecdysones that regulate the pupation of insects; application of azadirachtin interrupts the development and pupation of insects, eventually killing them.

<span class="mw-page-title-main">Carbamate</span> Chemical group (>N–C(=O)–O–)

In organic chemistry, a carbamate is a category of organic compounds with the general formula R2NC(O)OR and structure >N−C(=O)−O−, which are formally derived from carbamic acid. The term includes organic compounds, formally obtained by replacing one or more of the hydrogen atoms by other organic functional groups; as well as salts with the carbamate anion H2NCOO.

<span class="mw-page-title-main">Neem oil</span> Vegetable oil from the Indian neem tree

Neem oil, also known as margosa oil, is a vegetable oil pressed from the fruits and seeds of the neem, a tree which is indigenous to the Indian subcontinent and has been introduced to many other areas in the tropics. It is the most important of the commercially available products of neem, and its chemical properties have found widespread use as a pesticide in organic farming.

<span class="mw-page-title-main">Insect repellent</span> Substance which repels insects

An insect repellent is a substance applied to the skin, clothing, or other surfaces to discourage insects from landing or climbing on that surface. Insect repellents help prevent and control the outbreak of insect-borne diseases such as malaria, Lyme disease, dengue fever, bubonic plague, river blindness, and West Nile fever. Pest animals commonly serving as vectors for disease include insects such as flea, fly, and mosquito; and ticks (arachnids).

<i>Melia azedarach</i> Species of plant

Melia azedarach, commonly known as the chinaberry tree, pride of India, bead-tree, Cape lilac, syringa berrytree, Persian lilac, Indian lilac, or white cedar, is a species of deciduous tree in the mahogany family, Meliaceae, that is native to Indomalaya and Australasia.

A biopesticide is a biological substance or organism that damages, kills, or repels organisms seen as pests. Biological pest management intervention involves predatory, parasitic, or chemical relationships.

Neem cake organic manure is the by-product obtained in the process of cold pressing of neem tree fruits and kernels, and the solvent extraction process for neem oil cake. It is a potential source of organic manure under the Bureau of Indian Standards, Specification No. 8558. Neem has demonstrated considerable potential as a fertilizer. For this purpose, neem cake and neem leaves are especially promising. Puri (1999), in his book on neem, has given details about neem seed cake as manure and nitrification inhibitor. The author has described that, after processing, neem cake can be used for partial replacement of poultry and cattle feed.

<span class="mw-page-title-main">Larvicide</span> Insecticide against the larval stage

A larvicide is an insecticide that is specifically targeted against the larval life stage of an insect. Their most common use is against mosquitoes. Larvicides may be contact poisons, stomach poisons, growth regulators, or (increasingly) biological control agents.

<span class="mw-page-title-main">Indoxacarb</span> Chemical compound

Indoxacarb is an oxadiazine pesticide developed by DuPont that acts against lepidopteran larvae. It is marketed under the names Indoxacarb Technical Insecticide, Steward Insecticide and Avaunt Insecticide. It is also used as the active ingredient in the Syngenta line of commercial pesticides: Advion and Arilon.

<i>Spodoptera eridania</i> Species of moth

Spodoptera eridania is a moth that is known to be a pest. They are one of the most important defoliators in the tropical and subtropical regions of the western hemisphere that feed heavily on plants while they are young, often resulting in skeleton leaves on their food plants. They are also heavy feeders on tomato in Florida. There is a lot of development in producing pesticides against the S. eridania, specifically a neem-based pesticide that can result in smaller and prolonged development. The wingspan is 33–38 mm. Adults are on wing year-round. The larvae feed on various weeds but prefer Amaranthus species and Phytolacca americana.

<span class="mw-page-title-main">Acetamiprid</span> Chemical compound

Acetamiprid is an organic compound with the chemical formula C10H11ClN4. It is an odorless neonicotinoid insecticide produced under the trade names Assail, and Chipco by Aventis CropSciences. It is systemic and intended to control sucking insects (Thysanoptera, Hemiptera, mainly aphids) on crops such as leafy vegetables, citrus fruits, pome fruits, grapes, cotton, cole crops, and ornamental plants. It is also a key pesticide in commercial cherry farming due to its effectiveness against the larvae of the cherry fruit fly.

An insect growth regulator (IGR) is a substance (chemical) that inhibits the life cycle of an insect. IGRs are typically used as insecticides to control populations of harmful insect pests such as cockroaches and fleas.

<span class="mw-page-title-main">Tefluthrin</span> Synthetic pyrethroid used as insecticide

Tefluthrin is the ISO common name for an organic compound that is used as a pesticide. It is a pyrethroid, a class of synthetic insecticides that mimic the structure and properties of the naturally occurring insecticide pyrethrin which is present in the flowers of Chrysanthemum cinerariifolium. Pyrethroids such as tefluthrin are often preferred as active ingredients in agricultural insecticides because they are more cost-effective and longer acting than natural pyrethrins. It is effective against soil pests because it can move as a vapour without irreversibly binding to soil particles: in this respect it differs from most other pyrethroids.

<span class="mw-page-title-main">Nimbin (chemical)</span> Chemical compound

Nimbin is a triterpenoid isolated from Neem. Nimbin is thought to be responsible for much of the biological activities of neem oil, and is reported to have anti-inflammatory, antipyretic, fungicidal, antihistamine and antiseptic properties.

<span class="mw-page-title-main">Antifeedant</span>

Antifeedants are organic compounds produced by plants to repel herbivores through distaste or toxicity. These chemical compounds are typically classified as secondary metabolites in that they are not essential for the metabolism of the plant, but instead confer longevity. Antifeedants exhibit a wide range of activities and chemical structures as biopesticides. Examples include rosin, which inhibits attack on trees, and many alkaloids, which are highly toxic to specific insect species, such as quassinoids against the diamondback moth. Samadera indica also has quassinoids used for insect antifeedant uses.

References

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  2. Sanderson K (August 2007). "Chemists synthesize a natural-born killer". Nature. 448 (7154): 630–1. Bibcode:2007Natur.448Q.630S. doi: 10.1038/448630a . PMID   17687288.
  3. Butterworth, J; Morgan, E (1968). "Isolation of a Substance that suppresses Feeding in Locusts". Chemical Communications (1): 23. doi:10.1039/C19680000023.
  4. Senthil-Nathan, S.; Kalaivani, K.; Murugan, K.; Chung, G. (2005). "The toxicity and physiological effect of neem limonoids on Cnaphalocrocis medinalis (Guenée) the rice leaffolder". Pesticide Biochemistry and Physiology. 81 (2): 113. doi:10.1016/j.pestbp.2004.10.004.
  5. Senthil-Nathan, S.; Kalaivani, K.; Murugan, K.; Chung, P.G. (2005). "Effects of neem limonoids on malarial vector Anopheles stephensi Liston (Diptera: Culicidae)". Acta Tropica. 96 (1): 47–55. doi:10.1016/j.actatropica.2005.07.002. PMID   16112073.
  6. "TreeAzin Systemic Insecticide". BioForest Technologies. Retrieved 2014-06-03.
  7. "Our Products". ParryAmerica, Inc. Archived from the original on 2015-02-19. Retrieved 2015-02-18.
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  14. Fountain, Michelle T.; Hopkin, Steve P. (2005). "Folsomia candida (Collembola): A "Standard" Soil Arthropod". Annual Review of Entomology . Annual Reviews. 50 (1): 201–222. doi:10.1146/annurev.ento.50.071803.130331. ISSN   0066-4170. PMID   15355236.
  15. 1 2 3 4 5 Kilani-Morakchi, Samira; Morakchi-Goudjil, Houda; Sifi, Karima (20 July 2021). "Azadirachtin-Based Insecticide: Overview, Risk Assessments, and Future Directions". Frontiers in Agronomy. 3: 676208. doi: 10.3389/fagro.2021.676208 .