Acetogenin

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Chemical structure of annonacin Annonacin.svg
Chemical structure of annonacin

Acetogenins are a class of polyketide natural products found in plants of the family Annonaceae. They are characterized by linear 32- or 34-carbon chains containing oxygenated functional groups including hydroxyls, ketones, epoxides, tetrahydrofurans and tetrahydropyrans. They are often terminated with a lactone or butenolide. [1] Over 400 members of this family of compounds have been isolated from 51 different species of plants. [2] Many acetogenins are characterized by neurotoxicity. [3]

Contents

Examples include:

Structure

Acetogenin core unit (mono-THF) Mono-THF acetogenin core.png
Acetogenin core unit (mono-THF)
Acetogenin terminal lactone ring core unit (unsaturated) Acetogenin 2.png
Acetogenin terminal lactone ring core unit (unsaturated)

Structurally, acetogenins are a series of C-35/C-37 compounds usually characterized by a long aliphatic chain bearing a terminal methyl-substituted α,β-unsaturated γ-lactone ring, as well as one to three tetrahydrofuran (THF) rings. [4] These THF rings are located along the hydrocarbon chain, along with a number of oxygenated moieties (hydroxyls, acetoxyls, ketones, epoxides) and/or double bonds. [4]

Examples of R-groups for selected acetogenins [4]
CompoundR1R2R3R4R5
4-deoxyannoreticuinOHOHHHH
Annonacin OHOHHOHH
Annopentocin AOHHHOHH
DispalinOAcOHHOHH
Donnaienin COHOHHOAcOH
GoniotetracinOHOHHOHH
MuricoreacinOHHHOHH
Tonkinin AOHOHOHH
UvaribononeOHOAcOHH

Research

Acetogenins have been investigated for their biological properties, but are a concern due to neurotoxicity. [5] [6] [7] [8] [9] Purified acetogenins and crude extracts of the common North American pawpaw ( Asimina triloba ) or the soursop ( Annona muricata ) remain under laboratory studies. [10]

Mechanism of action

Acetogenins inhibit NADH dehydrogenase, a key enzyme in energy metabolism. [11]

Related Research Articles

<i>Asimina</i> North American Genus of fruit trees

Asimina is a genus of small trees or shrubs described as a genus in 1763. Asimina is the only temperate genus in the tropical and subtropical flowering plant family Annonaceae. Asimina have large, simple leaves and large fruit. It is native to eastern North America and collectively referred to as pawpaw. The genus includes the widespread common pawpaw Asimina triloba, which bears the largest edible fruit indigenous to the United States. Pawpaws are native to 26 states of the U.S. and to Ontario in Canada. The common pawpaw is a patch-forming (clonal) understory tree found in well-drained, deep, fertile bottomland and hilly upland habitat. Pawpaws are in the same plant family (Annonaceae) as the custard apple, cherimoya, sweetsop, soursop, and ylang-ylang; the genus is the only member of that family not confined to the tropics.

<span class="mw-page-title-main">Soursop</span> Species of plant

Soursop is the fruit of Annona muricata, a broadleaf, flowering, evergreen tree. It is native to the tropical regions of the Americas and the Caribbean and is widely propagated. It is in the same genus, Annona, as cherimoya and is in the Annonaceae family.

<span class="mw-page-title-main">Annonaceae</span> Family of flowering plants

The Annonaceae are a family of flowering plants consisting of trees, shrubs, or rarely lianas commonly known as the custard apple family or soursop family. With 108 accepted genera and about 2400 known species, it is the largest family in the Magnoliales. Several genera produce edible fruit, most notably Annona, Anonidium, Asimina, Rollinia, and Uvaria. Its type genus is Annona. The family is concentrated in the tropics, with few species found in temperate regions. About 900 species are Neotropical, 450 are Afrotropical, and the remaining are Indomalayan.

<span class="mw-page-title-main">Cherimoya</span> Edible fruit-bearing species of the genus Annona

The cherimoya, also spelled chirimoya and called chirimuya by the Inca people, is a species of edible fruit-bearing plant in the genus Annona, from the family Annonaceae, which includes the closely related sweetsop and soursop. The plant has long been believed to be native to Ecuador and Peru, with cultivation practiced in the Andes and Central America, although a recent hypothesis postulates Central America as the origin instead, because many of the plant's wild relatives occur in this area.

<i>Annona</i> Genus of fruits and plants

Annona is a genus of flowering plants in the pawpaw/sugar apple family, Annonaceae. It is the second largest genus in the family after Guatteria, containing approximately 166 species of mostly Neotropical and Afrotropical trees and shrubs.

<i>Annona squamosa</i> Species of tree

Annona squamosa is a small, well-branched tree or shrub from the family Annonaceae that bears edible fruits called sugar-apples or sweetsops. It tolerates a tropical lowland climate better than its relatives Annona reticulata and Annona cherimola helping make it the most widely cultivated of these species. Annona squamosa is a small, semi-(or late) deciduous, much-branched shrub or small tree 3 to 8 metres tall similar to soursop.

<i>Eurytides marcellus</i> Species of butterfly

Eurytides marcellus, the zebra swallowtail, is a swallowtail butterfly native to the eastern United States and south-eastern Canada. It is the state butterfly of Tennessee. Its distinctive wing shape and long tails make it easy to identify, and its black-and-white-striped pattern is reminiscent of a zebra. The butterflies are closely associated with pawpaws, and are rarely found far from these trees. The green or black caterpillars feed on the leaves of various pawpaw species, while the adults feed on flower nectar and minerals from damp soil.

<span class="mw-page-title-main">Holton Taxol total synthesis</span>

The Holton Taxol total synthesis, published by Robert A. Holton and his group at Florida State University in 1994, was the first total synthesis of Taxol.

<i>Asimina triloba</i> Species of tree

Asimina triloba, the American papaw, pawpaw, paw paw, or paw-paw, among many regional names, is a small deciduous tree native to the eastern United States and Canada, producing a large, yellowish-green to brown fruit. Asimina is the only temperate genus in the tropical and subtropical flowering plant family Annonaceae, and Asimina triloba has the most northern range of all. Well-known tropical fruits of different genera in family Annonaceae include the custard-apple, cherimoya, sweetsop, ylang-ylang, and soursop.

Annonins are a group of chemical compounds classified as acetogenins. They are found in the extracts of Annona seeds. Annonin-based bioinsecticides are used to control Coleoptera (beetle) pests commonly found in stored organic cereal and beans in the country of Brazil. Other different types of annonin-based insecticides, derived from A. mucosa, fight off lepidopteran (moth) pests that infest cabbage leaves, also found in the tropical climates of Brazil. The benefit of using these bioinsecticides is their relatively low cost and no phytotoxicity. These annonin molecules act as overpowering inhibitors of complex I in the electron-transport chain in the mitochondria of quarry pests. In cell membranes of these same pests, annonins also inhibit coenzyme NADH, causing these arthropods to die.

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

Annonacin is a chemical compound with toxic effects, especially in the nervous system, found in some fruits such as the paw paw, custard apples, soursop, and others from the family Annonaceae. It is a member of the class of compounds known as acetogenins. Annonacin-containing fruit products are regularly consumed throughout the West Indies for their traditional medicine uses.

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

Uvaricin is a bis(tetrahydrofuranoid) fatty acid lactone that was first isolated in 1982 from the roots of the Annonaceae Uvaria acuminata. Uvaricin was the first known example in a class of compounds known as acetogenins. Acetogenins, which are found in plants of the family Annonaceae, seem to kill cells by inhibiting NADH dehydrogenase in the mitochondrion. A method to synthesize uvaricin was first published in 1998, and an improved stereoselective synthesis published in 2001.

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

Borane dimethylsulfide (BMS) is a complexed borane reagent that is used for hydroborations and reductions. The advantages of BMS over other borane reagents, such as borane-tetrahydrofuran, are its increased stability and higher solubility. BMS is commercially available at much higher concentrations than its tetrahydrofuran counterpart and does not require sodium borohydride as a stabilizer, which could result in undesired side reactions. In contrast, borane·THF requires sodium borohydride to inhibit reduction of THF to tributyl borate. BMS is soluble in most aprotic solvents.

<span class="mw-page-title-main">Reductions with samarium(II) iodide</span>

Reductions with samarium(II) iodide involve the conversion of various classes of organic compounds into reduced products through the action of samarium(II) iodide, a mild one-electron reducing agent.

The Juliá–Colonna epoxidation is an asymmetric poly-leucine catalyzed nucleophilic epoxidation of electron deficient olefins in a triphasic system. The reaction was reported by Sebastian Juliá at the Chemical Institute of Sarriá in 1980, with further elaboration by both Juliá and Stefano Colonna.

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

Bullatacin is a bis(tetrahydrofuranoid) fatty acid lactone found in some fruits from Annonaceae family. It is a member of the class of compounds known as acetogenins.

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

Annonamine is a benzylisoquinoline alkaloid isolated from Annona muricata, a plant commonly used in folk medicine by indigenous communities in Africa and South America. Structurally, it contains an aporphine core featuring a quaternary ammonium group.

<span class="mw-page-title-main">Bis(cyclopentadienyl)titanium(III) chloride</span> Chemical compound

Bis(cyclopentadienyl)titanium(III) chloride, also known as the Nugent–RajanBabu reagent, is the organotitanium compound which exists as a dimer with the formula [(C5H5)2TiCl]2. It is an air sensitive green solid. The complex finds specialized use in synthetic organic chemistry as a single electron reductant.

<i>Annona bullata</i> Species of flowering plant

Annona bullata is a species of plant in the family Annonaceae. It is native to Cuba. Achille Richard, the French botanist who first formally described the species, named it after the bubbled appearance of the spaces between the fine network of veins in the leaves.

<i>Asimina pygmaea</i> Species of plant

Asimina pygmaea, the dwarf pawpaw or gopher berry, is a species of plant in the family Annonaceae. It is native to Florida and Georgia in the United States. William Bartram, the American naturalist who first formally described the species using the basionym Annona pygmaea, named it after its dwarfed stature.

References

  1. Li, N.; Shi, Z.; Tang, Y.; Chen, J.; Li, X. (2008). "Recent Progress on the Total Synthesis of Acetogenins from Annonaceae" (PDF). Beilstein Journal of Organic Chemistry. 4 (48): 1–62. doi:10.3762/bjoc.4.48. PMC   2633664 . PMID   19190742.
  2. Bermejo, A.; Figadère, B.; Zafra-Polo, M.-C.; Barrachina, I.; Estornell, E.; Cortes, D. (2005). "Acetogenins from Annonaceae: Recent Progress in Isolation, Synthesis and Mechanisms of Action". Natural Product Reports. 22 (2): 269–303. doi:10.1039/B500186M. PMID   15806200. Erratum: "Back Matter". Natural Product Reports. 22 (3): 426. 2005. doi:10.1039/B503508M.
  3. Liaw, Chih-Chuang; Liou, Jing-Ru; Wu, Tung-Ying; Chang, Fang-Rong; Wu, Yang-Chang (2016). Acetogenins from Annonaceae. Progress in the Chemistry of Organic Natural Products. Vol. 101. pp. 113–230. doi:10.1007/978-3-319-22692-7_2. ISBN   978-3-319-22691-0. PMID   26659109.
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  5. Ana V. Coria-Téllez; Efigenia Montalvo-Gónzalez; Elhadi M. Yahia; Eva N. Obledo-Vázquez (2018). "Annona muricata: A comprehensive review on its traditional medicinal uses, phytochemicals, pharmacological activities, mechanisms of action and toxicity". Arabian Journal of Chemistry. 11 (5): 662–691. doi: 10.1016/j.arabjc.2016.01.004 .
  6. Le Ven, J.; Schmitz-Afonso, I.; Touboul, D.; Buisson, D.; Akagah, B.; Cresteil, T.; Lewin, G. (2011). "Annonaceae fruits and parkinsonism risk: Metabolisation study of annonacin, a model neurotoxin; evaluation of human exposure". Toxicology Letters. 205: S50–S51. doi:10.1016/j.toxlet.2011.05.197.
  7. Victor R. Preedy; Ronald Ross Watson; Vinood B. Patel, eds. (2011). Nuts and Seeds in Health and Disease Prevention. Academic Press. pp. 434–435.
  8. Robert A. Levine; Kristy M. Richards; Kevin Tran; Rensheng Luo; Andrew L. Thomas & Robert E. Smith (2015). "Determination of Neurotoxic Acetogenins in Pawpaw (Asimina triloba) Fruit by LC-HRMS". J. Agric. Food Chem. 63 (4): 1053–1056. doi:10.1021/jf504500g. PMID   25594104.
  9. Potts, L. F.; Luzzio, F. A.; Smith, S. C.; Hetman, M; Champy, P; Litvan, I (2012). "Annonacin in Asimina triloba fruit: Implication for neurotoxicity". Neurotoxicology. 33 (1): 53–8. doi:10.1016/j.neuro.2011.10.009. PMID   22130466.
  10. McLaughlin, J.L. (2008). "Paw paw and cancer: annonaceous acetogenins from discovery to commercial products". Journal of Natural Products. 71 (7): 1311–21. doi:10.1021/np800191t. PMID   18598079.
  11. Eposti, M (1 July 1994). "Natural substances (acetogenins) from the family Annonaceae are powerful inhibitors of mitochondrial NADH dehydrogenase (Complex I)". Biochemical Journal. 301 (1): 161–167. doi:10.1042/bj3010161. PMC   1137156 . PMID   8037664.