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Names | |
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IUPAC names
trans-4,7-Dioxadispiro[4.0.46.25]dodeca-1,9-diene-3,8-dione
trans-1,7-Dioxadispiro[4.0.4.2]dodeca-3,9-diene-2,8-dione[1] | |
Identifiers | |
3D model (JSmol)
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ChEMBL | |
ChemSpider | |
PubChem CID
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UNII | |
CompTox Dashboard (EPA)
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Properties | |
C10H8O4 | |
Molar mass | 192.170 g·mol−1 |
Appearance | Colourless, odourless solid |
Density | 1.45g/cm3 |
Melting point | 158[1] °C (316 °F; 431 K) |
Boiling point | 535.7 °C (996.3 °F; 808.9 K) @ 760mmHg |
low | |
Solubility in chloroform | very soluble[1] |
Hazards | |
Flash point | 300.7 °C (573.3 °F; 573.8 K) |
Lethal dose or concentration (LD, LC): | |
LD50 (median dose)
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150 mg·kg−1 (mouse, i. p.) |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Anemonin is a tri-spirocyclic dibutenolide natural product found in members of the buttercup family (Ranunculaceae) such as R. bulbosus, R. ficaria, R. sardous, R. sceleratus,[2] and C. hirsutissima.[3] Originally isolated in 1792 by M. Heyer,[4] It is the dimerization product of the toxin protoanemonin.[5] One of the likely active agents in plants used in Chinese medicine as an anti-inflammatory[6] and Native American medicine as a horse stimulant,[3] its unique biological properties give it pharmaceutical potential as an anti-inflammatory and cosmetic agent.
Anemonin is a homodimer formed from two protoanemonin subunits. Protoanemonin is formed from the enzymatic cleavage of ranunculin upon crushing plant matter.[4] When a plant from this family is injured, a β-glucosidase cleaves ranunculin, liberating protoanemonin from glucose as a defense mechanism.[7] This butenolide readily dimerizes in aqueous media to form a single cyclodimer.[4]
Despite multiple possibilities, X-ray crystallography of the solid anemonin has revealed that the two rings exclusively possess a trans relationship.[8] The central cyclobutane ring was found to be bent to a dihedral angle of 152°. NMR spectroscopy reveals that the central ring is also twisted 9-11°.[9]
The highly selective formation of the head-to-head dimer has been rationalized through the stability of a proposed diradical intermediate; the resulting radicals after an initial carbon-carbon bond forming step are delocalized through the α,β-unsaturated system.[4] These proposed radicals could also be stabilized through the captodative effect, as they are situated between the enone and sp3-hybridized oxygen of the butenolides.
Destabilizing dipole-dipole interactions are proposed to disfavor the transition state where the two butenolide rings adopt a cis conformation, leading to selectivity of a trans relationship between the lactone rings.[4]
The formation of anemonin from protoanemonin is most likely a photochemical process. When Kataoka et. al compared the dimerization of protoanemonin in the presence and absence of radiation from a mercury lamp, they found a 75% yield with radiation and a very poor yield without radiation. It is not mentioned whether light was excluded from this control reaction; the low yield of anemonin may arise from visible light-mediated dimerization of protoanemonin.[10]
Anemonin possesses anti-inflammatory properties rather than the vesicant properties of its parent monomer. Numerous studies have demonstrated anemonin’s potential in treating ulcerative colitis,[11] cerebral ischemia,[12] and arthritis.[13][14] Its activity against LPS-related inflammation[13][15] and nitric oxide production[16][6] contribute to its pharmaceutical potential. Anemonin also displays inhibition of melanin production in human melanocytes with mild cytotoxicity.[17]
Given its skin permeability in ethanolic solutions[18] and its anti-inflammatory and anti-pigmentation properties, anemonin may be a good candidate for topical formulations as arthritis medications or cosmetics. An extraction method with the potential for industrial-scale preparations of anemonin may provide inroads to drug development.[19]