2.3.3.2 Methoxsalen
Synonyms Xanthotoxin; Meloxine; Ammoidin; Meladinine; 8-Methoxypsoralen; 8-MOP; 8-MP; Oxsoralen.
Biological Source Methoxsalen is a naturally occurring analogue of psoralen, found in various species of Rutaceae, Leguminosae, and Umbelliferae. It is obtained from the fruits of Fragara xanthoxyloides and the fruits of Ammi majus belonging to the natural order Umbelliferae. It is also found in the herb Ruta graveolens (Rutaceae).
Chemical Structure
9-Methoxy-7H-furol [3,2-g][1] benzopyran-7-one; (C12H8O4).
Isolation The various steps involved are as under:
1. The A. majus fruits are dried, powdered, sieved and extracted with petroleum ether to complete exhaustion.
2. The petroleum ether extract is filtered and concentrated to obtain a dark green semi-crystalline solid mass (crude methoxalen) crystallizes out.
Note: The petroleum ether layer is carefully deeanted off while hot and reserved separately for the isolation of imperatorin.
3. The residual dark-green solid mass is dissolved in minimum quantity of ethanol and boiled over an electric water-bath for 45-60 minutes. The contents are filtered immediately and the filtrate is concentrated under vacuo. It is cooled in a refrigerator overnight when pale-green crystals separate out. The crystals of methoxsalen thus obtained are purified first by washing with boiling water and finally recrystallizing from ethyl acetate.
Characteristic Features
1. It is obtained in two forms: first—as silky needles either from hot water or benzene + petroleum ether; secondly—as long rhombic prisms from ethanol + ether, having mp 148°C.
2. It is odourless but has a distinct bitter taste followed by tingling sensation.
3. It has uvmax: 219, 249, 300 nm (log ε 4.32, 4.35, 4.06).
4. It has a pH 5.5.
5. Solubility Profile: It is practically insoluble in cold water; sparingly soluble in boiling water,
liquid petroleum, ether; soluble in boiling ethanol, acetone, acetic acid, vegetable fixed oils, propylene glycol, benzene; freely soluble in chloroform; and soluble in aqueous alkalies with ring cleavage, but is reconstituted upon neutralization.
Identification Tests These are as follows:
1. A few crystals of methoxsalen on being triturated with little sulphuric acid in a porcelain dish produces an orange-yellow colour that gets changed to light green finally.
2. Wagner’s Reagent Test: Xanthotoxin gives an instant precipitate with Wagner’s Reagent (I2 + KI).
3. HNO3 Test: It gives a distinct yellow colouration with dilute HNO3, which on rendering to alkaline with KOH or NaOH, changes to crimson colour.
Uses
1. It is used extensively in the treatment of leukoderma.
2. It is employed as a pigmentation agent.
3. It is also used in the treatment of psoriasis and mycosis fungoides.
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* T.F. Anderson, J.J. Voorhees, Ann. Rev. Pharmacol. Toxicol., 20, 235 (1980); Vitiligo: An acquired cutaneous disorder characterised by white patches, surrounded by areas of normal pigmentation.
** A. Kornhauser et al., Science, 217, 733 (1982); Psoriasis: A common chronic disease of the skin consisting of erythematous papules that coalesce to form plaques with distinct borders.
*** B.J. Parsons, Photochem. Photobiol., 32, 813-821 (1980); Mycosis Fungoides: A non-Hodgkin's form of cutaneous
T-cell lymphoma of unknown etiology caused by a fungus.
