8-Methoxypsoralen CAS 298-81-7
Introduction：Basic information about 8-Methoxypsoralen CAS 298-81-7, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.
8-Methoxypsoralen Basic informationDescription References
| Product Name: | 8-Methoxypsoralen |
| Synonyms: | 2-g)(1)benzopyran-7-one,9-methoxy-7h-furo(;2-g][1]benzopyran-7-one,9-methoxy-7h-furo[;8-Methoxy-2',3',6,7-furocoumarin;8-methoxy-2’,3’,6,7-furocoumarin;8-Methoxy-4',5',6,7-furocoumarin;8-Methoxy-4',5':6,7-furocoumarin;8-methoxy-4’,5’,6,7-furocoumarin;8-methoxy-4’,5’:6,7-furocoumarin |
| CAS: | 298-81-7 |
| MF: | C12H8O4 |
| MW: | 216.19 |
| EINECS: | 206-066-9 |
| Product Categories: | Cytochrome P450 isozyme;This product is manufactured in GMP workshop.;Aromatics;Heterocycles;Intermediates & Fine Chemicals;Pharmaceuticals;Other APIs;Inhibitors;chemical reagent;pharmaceutical intermediate;phytochemical;reference standards from Chinese medicinal herbs (TCM).;standardized herbal extract;OXSORALENE;API;john's |
| Mol File: | 298-81-7.mol |
8-Methoxypsoralen Chemical Properties
| Melting point | 148-150 °C(lit.) |
| Boiling point | 276.6°C (rough estimate) |
| density | 1.1344 (rough estimate) |
| refractive index | 1.4270 (estimate) |
| storage temp. | Sealed in dry,Room Temperature |
| solubility | H2O: slightly soluble |
| form | Needle-Like Crystals or Powder |
| color | white to yellow |
| Water Solubility | PRACTICALLY INSOLUBLE |
| Merck | 14,5988 |
| BRN | 196453 |
| Major Application | cleaning products cosmetics food and beverages personal care |
| InChI | 1S/C12H8O4/c1-14-12-10-8(4-5-15-10)6-7-2-3-9(13)16-11(7)12/h2-6H,1H3 |
| InChIKey | QXKHYNVANLEOEG-UHFFFAOYSA-N |
| SMILES | COc1c2OC(=O)C=Cc2cc3ccoc13 |
| LogP | 1.523 (est) |
| CAS DataBase Reference | 298-81-7(CAS DataBase Reference) |
| IARC | 1 (Vol. 24, Sup 7, 100A) 2012 |
| NIST Chemistry Reference | Methoxsalen(298-81-7) |
| EPA Substance Registry System | Methoxsalen (298-81-7) |
Safety Information
| Hazard Codes | Xn,T |
| Risk Statements | 22-43-46-45-34 |
| Safety Statements | 36/37-53-45-36/37/39-26 |
| RIDADR | 3216 |
| WGK Germany | 3 |
| RTECS | LV1400000 |
| F | 10 |
| TSCA | TSCA listed |
| HS Code | 29322090 |
| Storage Class | 11 - Combustible Solids |
| Hazard Classifications | Acute Tox. 4 Oral Carc. 2 Muta. 2 Skin Sens. 1 |
| Hazardous Substances Data | 298-81-7(Hazardous Substances Data) |
| Toxicity | LD50 i.p. in rats: 470 ±30 mg/kg (Hakim) |
| Description | 8-methoxypsoralen (also known as methoxsalen) is a naturally occurring furocoumarin compound existing in several species of plants such as Psoralea corylifolia. It is a photoactive substance that can form DNA adducts upon UVA irradiation. It is a drug used for the treatment of psoriasis, eczema, vitiligo, and some kinds of cutaneous lymphomas associated with the exposure of skin to the UVA or light from lamps or sunlight. Its mechanism of action is through inhibiting the synthesis of the deoxyribonucleic acid (DNA). After the activation, it can preferentially bind to the guanine and cytosine molecules of DNA, further leading to the cross-linking of DNA, thus inhibiting the DNA synthesis. It can further inhibit the RNA and protein synthesis at high concentration. It is extracted from Ammi majus. |
| References | https://www.drugbank.ca/drugs/DB00553 https://en.wikipedia.org/wiki/Methoxsalen |
| Description | 8-Methoxypsoralen (8-MOP) and other psoralens are naturallyfound in plants, including common fruit and vegetable crops. |
| Chemical Properties | White to cream-colored, crystallinesolid; odorless. Slightly soluble in alcohol; practically insoluble in water. Combustible. |
| Originator | Oxsoracen,Eider,US,1955 |
| Uses | 8-Methoxypsoralen, is used in Photochemotherapy (methoxsalen with long wave ultraviolet radiation) is indicated for the repigmentation of idiopathic vitiligo. It is also used in Photopheresis (methoxsalen with long wave ultraviolet radiation of white blood cells) is indicated for use with the UVAR* System in the palliative treatment of the skin manifestations of cutaneous T-cell lymphoma. |
| Uses | antipsoriatic, pigmentation agent |
| Uses | Naturally occurring analog of Psoralen (P839800). Use in treatment of psoriasis and mycosis fungoides. |
| Uses | For the treatment of psoriasis and vitiligo |
| Uses | A potent suicide inhibitor of cytochrome P-450. |
| Uses | Naturally occurring analog of psoralen. Use in treatment of psoriasis and mycosis fungoides |
| Indications | Methoxsalen has effects similar to those of trioxsalen. Methoxsalen is superiorto trioxsalen in producing erythema and tanning and is the drug used in PUVAtherapy. Methoxsalen is also available as a 1% lotion. |
| Definition | ChEBI: A member of the class of psoralens that is 7H-furo[3,2-g]chromen-7-one in which the 9 position is substituted by a methoxy group. It is a constituent of the fruits of Ammi majus. Like other psoralens, trioxsalencauses photosensitization of the skin. It is administered topically or orally in conjunction with UV-A for phototherapy treatment of vitiligo and severe psoriasis. |
| Manufacturing Process | It has been found that the compound 8-geranoxy psoralen is present in citrusoils, particularly lemon and lime oils. This compound can be isolated from theoil by a process which involves primarily absorption on an adsorbent materialfollowed by elution with a suitable solvent. (A) Cleavage of 8-Geranoxypsoralen: 275 mg of 8-geranoxypsoralen wasdissolved with mechanical stirring in 4 ml glacial acetic acid. After 10 minutes,one drop of concentrated sulfuric acid was added to the solution. In 4 minutesthereafter a light tan precipitate began to form. Stirring was continued for 35minutes and the reaction mixture was refrigerated for one hour and 20minutes. The precipitate was then removed by suction filtration and washedon the filter with glacial acetic acid followed by ice-cold ethyl ether. Theproduct, 8-hydroxypsoralen, weighed 115 mg, that is, 74% of theory. (B) Methylation of 8-Hydroxypsoralen: 115 mg of 8-hydroxypsoralen wasdissolved in 10 ml absolute methanol, an excess of diazomethane dissolved inether was added and the mixture allowed to stand at room temperature withoccasional stirring for 3 hours. The next day the reaction mixture was reducedin volume to 3 ml by evaporation on the steam bath and the concentrate washeld in a refrigerator overnight. The next day, fine needles (80 mg) of 8-methoxypsoralen were filtered from the solution. The compound had a MP of145 to 146°C and was obtained in a yield of 65% of theory. There is also a wholly synthetic route to Methoxsalen as outlined by Kleemanand Engel. |
| Brand name | 8-Mop (Valeant); Oxsoralen (Valeant); Uvadex (Therakos). |
| Therapeutic Function | Dermal pigmentation enhancer |
| General Description | Odorless white to cream-colored crystalline solid. Bitter taste followed by tingling sensation. |
| Air & Water Reactions | Sensitive to light and air. Insoluble in water. |
| Reactivity Profile | 8-Methoxypsoralen is incompatible with strong oxidizing agents. |
| Fire Hazard | Flash point data for 8-Methoxypsoralen are not available; however, 8-Methoxypsoralen is probably combustible. |
| Contact allergens | This fur(an)ocoumarin is an phototoxic compoundthat causes phototoxic dermatitis. Many plants of theApiaceae–Umbelliferae and most of the Rutaceae familycontain 5-methoxypsoralen and 8-methoxypsoralen.Their spectra is in the UVA range (300–360 nm). It isused in combination with UVA to treat various skindisorders such as psoriasis. |
| Safety Profile | Confirmed carcinogen.Poison by intraperitoneal route. Moderatelytoxic by ingestion and subcutaneous routes.Human mutation data reported. Whenheated to decomposition it emits acridsmoke and irritating fumes. A drug used totreat slun diseases. |
| Environmental Fate | The industrial use of 8-MOP results in its release into theenvironment through multiple pathways, and its existence asa natural substance in plants further expands exposure to theenvironment. Airborne 8-MOP will exist in the vapor andparticulate phases, and will be degraded in air by reaction withphotochemically produced hydroxyl radicals, with an estimatedhalf-life of approximately 1.2 h, it may also be subject todirect photolysis by sunlight. Particulate 8-MOP will beremoved from the atmosphere by wet or dry deposition. Ifreleased into the soil, it is expected to have high mobility and isnot expected to volatilize. 8-MOP does not biodegrade. Inaqueous environments, 8-MOP is not expected to hydrolyze, itwill, however, adsorb to suspended solids and sediment. Dueto 8-MOP’Ks resistance to degradation by many routes, it isexpected to remain in the environment for a prolonged period,and as such will also be subject to long-range transport. 8-MOPhas an estimated bioconcentration factor (BCF) of 9, meaningthat bioconcentration and bioaccumulation are low in aquaticorganisms. |
| Purification Methods | Purify xanthotoxin by recrystallisation from *C6H6/pet ether (b 60-80o) to give silky needles, or from EtOH/Et2O to give rhombic prisms or from hot H2O to give needles. It is soluble in aqueous alkali due to ring opening of the cyclic lactone but recyclises upon acidification. It has UV max in EtOH at 219, 249 and 300nm (log 4.32, 4.35 and 4.06) and 1H NMR in CDCl3 with at 7.76 (d, 1H, J 10 Hz), 7.71 (d, 1H, J 2.5 Hz), 7.38 (s, 1H), 6.84 (d, 1H, J 2.5 Hz), 6.39 (d, 1H, J 10 Hz) and 4.28 (s, 3H)ppm. [Nore & Honkanen J Heterocycl Chem 17 985 1980.] It is a DNA intercalator, is used in the treatment of dermal diseases, and is a human carcinogen [Tessman et al. Biochemistry 24 1669 1985.] [Beilstein 19 I 711, 19/6 V 15.] |
| Toxicity evaluation | The toxic effects of psoralens almost never occur withoutexposure to UV light. These are photosensitizing materials thatexert their primary effect on the skin. 8-MOP, when activatedby long-wavelength UV light in the range of 320–400 nm, isstrongly erythemogenic, melanogenic, and cytotoxic in theepidermis. The mechanisms of action of 8-MOP in inducingrepigmentation of vitiliginous skin have not been established.Repigmentation depends on the presence of functioningmelanocytes and UV light. 8-MOP may activate the functionaland dihydroxyphenylalanine-positive melanocytes present invitiliginous skin. An increase in the activity of tyrosinase, theenzyme that catalyzes the conversion of tyrosine to dihydroxyphenylalanine(a precursor of melanin), has been shown in melanin-producing cells exposed in vitro to trioxsalen and UVAlight. In addition, binding of photoactivated psoralens (intriplet states) to pyrimidine bases of nucleic acids, withsubsequent inhibitions of DNA synthesis, cell division, andepidermal turnover, has been demonstrated. Following photoactivation,8-MOP forms covalent bonds with DNA toproduce monofunctional (addition to a single strand of DNA)and bifunctional adducts (cross-linking to both strands ofDNA). Reactions with other proteins also occur. Psoralens mayalso increase melanin formation by producing an inflammatoryreaction in the skin. Other mechanisms of increasedpigmentation may include an increase in the number of functionalmelanocytes (and possibly activation of dormantmelanocytes); enhancement of melanin granule synthesis;stimulation of the movement of melanocytes up hair folliclesresulting in melanocytic repopulation of the epidermis; and/orhypertrophy of melanocytes and increased arborization of theirdendrites. Since psoriasis is a hyperproliferative disorder andother agents effective in the treatment of psoriasis are known toinhibit DNA synthesis, the therapeutic effect of 8-MOP in thetreatment of psoriasis probably involves binding to DNA andinhibition of DNA synthesis resulting in decreased cell proliferation;other vascular, leukocyte, or cell regulatory mechanismsmay be involved. It has been suggested that at low drugload, 8-MOP binds to DNA as an intercalator, whereas at higherratios of 8-MOP to DNA, it binds to the outside of DNA,probably in the minor groove and causes some compaction inDNA. Protective eyewear is used to prevent irreversible bindingof 8-MOP to proteins and DNA components of the lens. Thecentral hypothesis for the reproductive toxicity of 8-MOP isthat it produces reproductive effects by disrupting the hypothalamus–pituitary axis, and the alternative hypothesis is thatthis compound targets gonadal function, resulting in alterationof pregnancy outcome. |
8-Methoxypsoralen Preparation Products And Raw materials
| Raw materials | Sulfuric acid-->8-GERANOXYPSORALEN-->Diazomethane-->7-HYDROXY-8-METHOXYCOUMARIN-->XANTHOTOXOL |
| Preparation Products | 5-Hydroxyxanthotoxin |
