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| Names | |
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| 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 |
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| ECHA InfoCard | 100.115.924 |
| KEGG |
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| UNII | |
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| Properties | |
| C35H44O16 | |
| Molar mass | 720.721 g·mol−1 |
Except where otherwise noted, data are given for materials in theirstandard state (at 25 °C [77 °F], 100 kPa). | |
Azadirachtin, achemical compound belonging to thelimonoid group, is asecondary metabolite present inneem seeds. It is a highly oxidizedtetranortriterpenoid which boasts a plethora of oxygen-bearing functional groups, including anenol ether, acetal,hemiacetal, tetra-substitutedepoxide and a variety ofcarboxylic esters.
Azadirachtin has a complex molecular structure; it presents both secondary and tertiary hydroxyl groups and atetrahydrofuran ether in itsmolecular 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 ofsynthetic 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 ofSteven Ley at theUniversity of Cambridge in 2007.[1][2] The described synthesis was arelay approach, with the required, heavily functionalizeddecalin 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.
Initially found to be active as a feeding inhibitor towards thedesert locust (Schistocerca gregaria),[3] it is now known to affect over 200 species ofinsects, by acting mainly as an antifeedant and growth disruptor. Azadirachtin exhibits considerable toxicity towardsAfrican cotton leafworm (Spodoptera littoralis), which are resistant to a commonly used biological pesticide,Bacillus thuringiensis. Azadirachtin fulfills many of the criteria needed for a goodinsecticide. Azadirachtin isbiodegradable (it degrades within 100 hours when exposed to light and water) and shows very lowtoxicity tomammals (theLD50 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 theneem tree,Azadirachta indica (hence the prefix aza does not imply anaza compound, but refers to thescientific 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 thebiocontrol agentBeauveria.[13]
Nimbecidine is a natural product insecticide mix which is mostly azadirachtin, with some otherlimonoids.[14]
Azadirachtin interferes with a wide variety of insect pathways.[15]
Azadirachtin is formed via an elaborate biosynthetic pathway, but is believed that the steroidtirucallol is the precursor to the neemtriterpenoid secondary metabolites. Tirucallol is formed from two units offarnesyl diphosphate (FPP) to form a C30 triterpene, but then loses three methyl groups to become a C27 steroid. Tirucallol undergoes an allylic isomerization to formbutyrospermol, which is then oxidized. The oxidized butyrospermol subsequently rearranges via aWagner-Meerwein 1,2-methyl shift to formapotirucallol.
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 afuran ring and the molecule is oxidized further to form azadirone andazadiradione. The third ring is then opened and oxidized to form the C-seco-limonoids such asnimbin,nimbidinin andsalannin, which has beenesterified with a molecule oftiglic acid, which is derived fromL-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.
