psoralen

Psoralen
IUPAC name	7H-furo[3,2-g]chromen-7-one or 7H-furo[3,2-g]benzopyran-7-one
Identifiers
CAS number	66-97-7 Y
SMILES	O=C1OC2=CC3=C (C=CO3)C=C2C=C1
Properties
Molecular formula	C11H6O3
Molar mass	186.16 g/mol
Melting point	158-161 °C
Y (what is this?)  (verify) Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
Infobox references

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Psoralen (also called psoralene) is the parent compound in a family of natural products known as furocoumarins. It is structurally related to coumarin by the addition of a fused furan ring, and may be considered as a derivative of umbelliferone. Psoralen occurs naturally in the seeds of Psoralea corylifolia, as well as in the common Fig, celery, parsley and West Indian satinwood. It is widely used in PUVA (=Psoralen +UVA) treatment for psoriasis, eczema, vitiligo, and Cutaneous T-cell Lymphoma. Although safe to mammals, it should be used with care since many furocoumarins are extremely toxic to fish, and some are indeed used in streams in Indonesia to catch fish.

Uses

An important use of psoralen is in PUVA treatment for skin problems such as psoriasis and (to a lesser extent) eczema and vitiligo. This takes advantage of the high UV absorbance of psoralen. The psoralen is applied first to sensitise the skin, then UVA light is applied to clean up the skin problem. Psoralen has also been recommended for treating alopecia. Psoralens are also used in photopheresis where they are mixed with the extracted leukocytes before UV radiation is applied.

Psoralen is a significant mutagen and is used for this purpose in molecular biology research.

Despite the photocarcinogenic properties of psoralen,^{[1] [2]} It had been used as a tanning activator in sunscreens until 1996.^[3] Psoralens are used in tanning accelerators, but users should keep in mind that psoralen increases your skin’s sensitivity to light. Some patients have even had severe skin loss after sunbathing with psoralen containing tanning activators.[1] Patients with lighter skin colour suffer four times as much from the melanoma-generating properties of psoralens than those with darker skin^[3]

Chemistry

One isomer of psoralen is angelicin, and most furocoumarins can be regarded as derivatives of psoralen or angelicin. Some important psoralen derivatives are Imperatorin, xanthotoxin, bergapten and nodekenetin.

Another important feature of this class of compounds is its ability in generating singlet oxygen.

Structure

The structure of psoralen was originally deduced using its degradation reactions. It exhibits the normal reactions of the lactone of coumarin, such as ring opening by alkali to give a coumarinic acid or coumaric acid derivative. Potassium permanganate causes oxidation of the furan ring, while other methods of oxidation produce furan-2,3-carboxylic acid.

Synthesis

Psoralen synthesis is challenging, due the fact that umbelliferone undergoes substitution at the 8-position rather than at the desired 6 position. Benzofuran reacts preferentially in the furan ring rather than in the benzene ring. However the 6-hydroxy derivative of 2,3-dihydrobenzofuran (also called coumaran) does undergo substitution as desired allowing the following synthesis of the coumarin system via a Gattermann-Koch reaction followed by a Perkin condensation using acetic anhydride. The synthesis is then completed by dehydrogenation of the five-membered ring to produce the furan ring.

Biosynthesis

Psoralen originates from coumarins of the shikimate pathway; its biosynthesis is shown in the figure below. The aromatic ring in 6 is activated at positions ortho to the hydroxyl group, and is alkylated by 5, an alkylating agent. The dimethylallyl group in 7 then undergoes cyclization with the phenol group to give 8. This transformation is catalysed by a cytochome P-450-dependent monooxygenase17 (psoralen 5-monooxygenase), and cofactors (NADPH) and molecular oxygen.^[4]

Another biosynthesis pathway of psoralen is shown below in the figure. A second P-450-dependent monooxygenase enzyme (psoralen synthase) then cleaves off 10 (in the form of 11) from 8 to give 1. This pathway does not involve any hydroxylated intermediate, and cleavage is postulated to be initiated by a radical reaction. ^[5]

External links

• Institute for Traditional Medicine vitiligo article
• ibiblio page on Psoralea corylifolia
• USDA ARS info on uses & plants

References

Further reading

1. F. M. Dean Naturally Occurring Oxygen Ring Compounds, Butterworths, London, 1963.
2. The Merck Index, 7th edition, Merck & Co, Rahway, New Jersey, US, 1960.