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]
Examples include:
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]
Compound | R1 | R2 | R3 | R4 | R5 |
---|---|---|---|---|---|
4-deoxyannoreticuin | OH | OH | H | H | H |
Annonacin | OH | OH | H | OH | H |
Annopentocin A | OH | H | H | OH | H |
Dispalin | OAc | OH | H | OH | H |
Donnaienin C | OH | OH | H | OAc | OH |
Goniotetracin | OH | OH | H | OH | H |
Muricoreacin | OH | H | H | OH | H |
Tonkinin A | OH | OH | O | H | H |
Uvaribonone | OH | OAc | O | H | H |
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]
Acetogenins inhibit NADH dehydrogenase, a key enzyme in energy metabolism. [11]
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. Fossils date to the Cretaceous.
Tetrahydrofuran (THF), or oxolane, is an organic compound with the formula (CH2)4O. The compound is classified as heterocyclic compound, specifically a cyclic ether. It is a colorless, water-miscible organic liquid with low viscosity. It is mainly used as a precursor to polymers. Being polar and having a wide liquid range, THF is a versatile solvent. It is an isomer of another solvent, butanone.
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.
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.
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 practised 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.
Annona or Anona 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.
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. It is a native of tropical climate in the Americas and West Indies, and Spanish traders aboard the Manila galleons docking in the Philippines brought it to Asia.
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.
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.
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 southern Ontario, 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.
Sodium cyanoborohydride is a chemical compound with the formula Na[BH3(CN)]. It is a colourless salt used in organic synthesis for chemical reduction including that of imines and carbonyls. Sodium cyanoborohydride is a milder reductant than other conventional reducing agents.
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.
Lithium triethylborohydride is the organoboron compound with the formula LiEt3BH. Commonly referred to as LiTEBH or Superhydride, it is a powerful reducing agent used in organometallic and organic chemistry. It is a colorless or white liquid but is typically marketed and used as a THF solution. The related reducing agent sodium triethylborohydride is commercially available as toluene solutions.
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.
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.
Borane dimethylsulfide (BMS) is a chemical compound with the chemical formula BH3·S(CH3)2. It is an adduct between borane molecule and dimethyl sulfide molecule. It 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, BH3·THF requires sodium borohydride to inhibit reduction of THF to tributyl borate. BMS is soluble in most aprotic solvents.
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.
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.
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.
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.