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| Names | |
|---|---|
| Preferred IUPAC name 4-Methoxy-7H-furo[3,2-g][1]benzopyran-7-one | |
Other names
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| Identifiers | |
3D model (JSmol) | |
| ChEBI | |
| ChEMBL | |
| ChemSpider | |
| ECHA InfoCard | 100.006.913 |
| EC Number |
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| KEGG | |
| UNII | |
| UN number | 1759 |
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| Properties | |
| C12H8O4 | |
| Molar mass | 216.192 g/mol |
| Pharmacology | |
| D05BA03 (WHO) | |
Except where otherwise noted, data are given for materials in theirstandard state (at 25 °C [77 °F], 100 kPa). | |
Bergapten (5-methoxypsoralen) is a naturally-occurring organic chemical compound produced by numerous plant species, especially from the carrot familyApiaceae and the citrus familyRutaceae. For example, bergapten has been extracted from 24 species of the genusHeracleum in the family Apiaceae.[1][2] In the family Rutaceae, variousCitrus species contain significant amounts of bergapten,[3] especially thebergamot orange, themicrantha, and certain varieties oflime andbitter orange.
Bergapten belongs to a class of chemical compounds known as thefuranocoumarins. In 1834, Kalbrunner isolated 5-methoxypsoralen frombergamot essential oil,[4] hence the common name "bergapten". It was the first furanocoumarin to be isolated and identified.
Bergapten is a derivative ofpsoralen, the parent compound of a family of naturally-occurring organic compounds known as the linear furanocoumarins (so called since they exhibit a linear chemical structure). Some of the linear furanocoumarins, including bergapten, act as strongphotosensitizers when applied topically to the skin.
Bergapten is often found in plants associated withphytophotodermatitis,[5] a potentially serious skin inflammation. Contact with plant parts containing bergapten (and other linear furanocoumarins) followed by exposure toultraviolet light may lead to phytophotodermatitis. In particular, bergapten appears to be the primaryphototoxic compound responsible forCitrus-induced phytophotodermatitis.[3]
Bergapten and other linear furanocoumarins induce a loss of template activity for RNA synthesis. 5-methoxypsoralen has also been noted for itsmutagenic effects as well as its capacity for being a very potent agent for inducingchromosome aberrations. With a high enough concentration, complete mitotic inhibition was observed.[4]
There is sufficient evidence that bergapten promotes cancer in animals but such evidence of carcinogenicity in humans is lacking. According to theInternational Agency for Research on Cancer, bergapten isprobably carcinogenic to humans.[6]
Bergapten serves to have the skin absorb more light, and pigmentary diseases likevitiligo (leukodermia) andpsoriasis have treatments involving furanocoumarins often in conjunction with sun exposure or solar radiation. In people who easily sunburn, furanocoumarins can also increase the tolerance of skin to solar radiation.[4] Bergapten was shown to elicit certain skin reactions in order to even out pigmentation lightening for vitiligo patients depending on various factors like the susceptibility of the subject, the dosage, and the humidity, but the effects may be inconsistent.[7]
With psoriasis, bergapten has been valued as an oralphotochemotherapy treatment for its efficacy and lack of phototoxic and drug-insensitive reactions. It operates as a photosensitizing drug that is as effective or, with high enough dosage, more effective than 8-methoxypsoralen in the clearance of psoriasis lesions.[8] It has been shown to be a valuable alternative to 8-methoxypsoralen due to the relative lack of side effects during treatment like erythma, pruritus, and nausea.[9]
Bergapten has also been implicated as a potential prevention method for sunlight-related skin cancer. One study found that a tan gained with bergapten had less DNA damage in human subjects.[10] Bergapten has been shown to have anti-tumoral effects, like its ability to induce theautophagic process in breast cancer cells. One study suggested that this was possible through the up-regulation ofPTEN gene expression in those breast cancer cells.[11]
Bergapten, alongside other furanocoumarins, has also been implicated inCytochrome P450 inhibition.[12]
Bergapten is a natural compound coming from plants like the common fig, but it can also be synthesized. Most syntheses of linear furanocoumarins involve starting with a central aromatic unit and adding two heterocyclic rings. Alternate routes of synthesis are desirable to avoid regiochemical problems and moderate yields. The synthesis described here involves Iodine as a removable group to insure regiochemical integrity and convergence.[13] As shown in the diagram, phloroglucinol (compound 1) was the starting material. Mono-methylation was conducted followed by a reaction with ethyl propiolate in the presence of ZnCl2 to yield 7-hydroxy-5-methoxycoumarin (product 3, not shown) with 68% yield. The 8-position of 7-hydroxy-5-methoxycoumarin was then protected by iodine to avoid the formation of an angular furanocoumarin. Product 4 in the diagram is the result of that iodine protection. Product 5 was the result of the allylation of product 4. Osmium tetraoxide and sodium metaperiodate were used to oxidatively cleave the O-allyl derivative onto the aldehyde product 7 via a diol intermediate (product 6, not shown). Cyclization of the aldehyde product 7 using BF3-Et2O in tetra-n-butylammonium bromide was then conducted to construct the furan ring. The final step was to remove the iodine protective group via Pd(OAc)2 to ultimately produce bergapten (product 9) with 90% yield. Synthetic bergapten was isolated as a colorless compound with properties spectroscopically identical to the natural product.
A known use of bergapten is in the synthesis ofFraxinol.[14] The key reaction in this synthesis is the oxidation of the furan ring of visnagin and bergapten with chromic acid.[14]