Description
Bergapten exists in roots, stems, and leaves of a variety of Rutaceae, Umbelliferae, and leguminous plants such as ephedra, fennel, and vetch.
Chemical Properties
Crystalline Solid
Physical properties
Appearance: Crystalline state is mercerizing white needled crystal. Autofluorescence can be observed under the excitation of UV at 432nm. By directly adding bergapten into sulfuric acid, the solution became golden. Because of the structure of coumarin lactone, hydroxamic acid iron reaction can be occurred. Solubility: It is soluble in chloroform; slightly soluble in benzene, ethyl acetate, and ethanol; and insoluble in water. It has a photosensitive activity. Crystalline state is mercerizing white needled crystal. Melting point: 181–183°C.
History
It was first isolated from a plant called Ammi majus L in 1947. It was first synthesized by JEAN and JACQUES in 1982. The efficacy of psoralen in the treatment of psoriasis and other skin diseases has been studied in modern medicine, and more and more studies have proven that the extracts and derivatives of psoralen have significant effect on the treatment of various skin diseases. Bergapten used in the treatment of PUVA (psoralen plus ultraviolet) and treatment of vitiligo has more than 20years of history. 8-Methoxypsoralen in the treatment of psoriasis frequently has a problem of phototoxicity and drug intolerance. Therefore, researchers have
studied 5-MOP (5-methoxypsoralen) on this basis. The results showed that the
5-methoxypsoralen has a close effect and fewer side effects of the treatment companies with the 8-methoxypsoralen with a double dose.
Uses
Naturally occurring analog of psoralen and isomer of methoxsalen. Found in a wide variety of plants. Antipsoriatic
Uses
Has been used to promote tanning in suntan preparations.
Uses
A psoralen phytotoxic citrus essential oil found in bergamont
Uses
antipsoriatic, antiinflammatory
Uses
Naturally occurring analog of Psoralen ( P839800) and metabolite of 8-Methoxy Psoralen (M260795). Antipsoriatic.
Definition
ChEBI: A 5-methoxyfurocoumarin that is psoralen substituted by a methoxy group at position 5.
General Description
Grayish-white microcrystalline powder or yellow fluffy solid.
Air & Water Reactions
Insoluble in water.
Reactivity Profile
Bergapten may be sensitive to exposure to light. A related chemical is incompatible with strong oxidizers.
Fire Hazard
Flash point data for Bergapten are not available; however, Bergapten is probably combustible.
Contact allergens
This fur(an)ocoumarin is an phototoxic compound
that causes phototoxic dermatitis. Many plants of the
Apiaceae–Umbelliferae and most of the Rutaceae family
contain 5-methoxypsoralen and 8-methoxypsoralen.
Their spectra is in the UVA range (300–360 nm). It is
used in combination with UVA to treat various skin
disorders such as psoriasis.
Pharmacology
Bergapten could be used to treat vitiligo mainly because it can be embedded between the thymine base pairs of DNA in darkness. Under UV light (365nm) double furan ring or pyran ring on the irradiation can occur halo reaction showed the structure and biological activity of thymine. The curative effect of high-dose 5-MOP (1.2–1.6mg/kg) in the treatment of UVA is better and has a less cure time.
As the main component of the drug, it can be used to treat different types of
psoriasis.
The study of Shikishima et al. showed that the bergapten has an anti-HIV
activity, which was mainly affected by HIV reverse transcriptase, protease, and integrase, and the IC50 value was 24.8 mg/L.
Modern pharmacological studies have shown that it has a certain inhibitory
activity on tumor and cell proliferation.
Clinical Use
It has the optical activity to the skin, has the function of killing the soft animal, has the anticoagulant function and the hemostatic effect against the heparin, and has the antimicrobial activity. In a trial for chemical therapy in the treatment of psoriasis patients, the result has shown that the drug can stimulate the melanin and increase the skin pigmentation, which is essential for the treatment of vitiligo.
Synthesis
Bergapten is obtained in 55% overall yield from phloroglucinol through monomethylation, Hoesch reaction, acetylation, deacetoxylation, Pechmann condensation and DDQ dehydrogenation[1].
In a second route, phloroglucinol is monomethylated to an anisole derivative, which reacts with ethyl propiolate in the presence of ZnCl2 to give 7-hydroxy-5-methoxycoumarin; the 8-position is then protected with iodine, allylated, oxidatively cleaved to the aldehyde with osmium tetraoxide and sodium metaperiodate, and finally deiodinated with Pd(OAc)2 to afford bergapten in 90% yield as colorless needles, mp 180–182 °C[2].
Purification Methods
Crystallise it from EtOH or aqueous MeOH, and it sublimes in vacuo. Its properties are similar to those of its 9-methoxy isomer (xanthotoxin, see below). It is slightly soluble in *C6H6, CHCl3 and AcOH but insoluble in H2O. Its fluorescence has ex at 352nm with em at 480nm. It is a DNA intercalator and possible carcinogen. [Howell & Robertson J Chem Soc 293 1937, Boyer et al. Biochemistry 27 3011 1988, Beilstein 19/6 V 4.]
References
[1]
Cai, X., Ji, D., Liu, J., Hu, M., Jin, Z. (2022). A New Approach to the Synthesis of Bergapten. Chemical Research in Chinese Universities, 38(6), 1492–1496.
https://doi.org/10.1007/s40242-022-2089-7 [2]
Oda, K., Nishizono, N., Tamai, Y., Yamaguchi, Y., Yoshimura, T., Wada, K., Machida, M. (2005). An Efficient Synthesis of Bergapten. HETEROCYCLES, 65(8), 1985.
https://doi.org/10.3987/com-05-10451
