Psoralen derivatives

Brand Name(s) 8-MOP, Oxsoralen, Oxsoralen-Ultra, Uvadex Chemical Class Psoralen derivative... 

Gravot, A. et al.. Cinnamic acid 4-hydroxylase mechanism-based inactivation by psoralen derivatives cloning and characterization of a C4H from a psoralen producing plant — Ruta graveolens — exhibiting low sensitivity to psoralen inactivation. Arch. Biochem. Biophys., 422, 71, 2004. 

Photochemically reactive molecules have often been used as labels for specific sites in proteins and nucleic acids. Psoralen derivatives serve as relatively nonspecific photochemically activated crosslinking agents for DNA and double-stranded RNA.195 Aryl azides are converted by light to aryl nitrenes, which react in a variety of ways including insertion into C-H bonds (Eq. 23-27).200 201 In some cases UV irradiation can be used to join natural substrates to enzymes or hormones to receptors. For example, progesterone, testosterone, and other steroids have been used for direct photoaffinity labeling of their receptors.202 Synthetic benzophenones have also been used widely as photoactivated probes.203... 

The demonstration of stepwise adduct formation by psoralens was an important advance. At 390 nm monoadduct formation occurs a crosslink is completed by irradiation at 360 nm (Chatterjee and Cantor, 1978). DNA-psoralen monoadducts have been used to covalently label complementary sites on large RNA molecules. The sites may then be mapped by electron microscopy of the denatured nucleic acid complexes (Wollenzien and Cantor, 1982). Psoralen derivatives for attachment to proteins have been made (Cantor, 1980) and this will allow the exploration of protein binding sites on nucleic acids by photochemical crosslinking. 

Citrus oil dominates this class of essential oil. It is obtained by the cold press method with the exception of lime oil, which is also prepared by steam distillation of essential oil separated during the production of juice.106,107 Aside from bergamot, these oils are primarily monoterpene hydrocarbon mixtures of which (if)-limonene (3) is usually the dominant compound. Since odor contribution of this monoterpene compound is low, it is often removed by distillation or repeated solvent extraction. The resulting oil rich in odor-active compounds is called terpeneless oil and is used extensively. In the case of bergamot and lemon oils, psoralen derivates like bergaptene (64) causing photosensitivity are problematic, and those for fragrance use are rectified to remove it (Table 8). 

A one-pot procedure to construct the key intermediate of natural product egonol was developed using carbene-alkyne coupling and oxidative aromatization as key steps <03T5609>. Novel tetracyclic psoralen derivatives were synthesized from commercially available 2-methoxyresorcinol through a series of synthetic transformations <03JMC3800>. 

Rapoport and coworkers have used a hydrogenation-dehydrogenation protocol to introduce tritium into psoralen derivatives (equation 101). For the same class of compounds, Heindel and coworkers have discovered a very simple catalytic transfer hydrogenation of the furan double bond (equation 102).I68.I69... 

Dalla Via, L., Uriarte, E., Quezada, E., Dolmella, A., Ferlin Maria, G., Gia, O. Novel pyrone side tetracyclic psoralen derivatives synthesis and photobiological evaluation. J. Med. Chem. 2003, 46, 3800-3810. 

The solid phase synthesis of oligonucleotides containing a site-specific modified psoralen derivative has been accomplished using reagent 197. The base... 

E5, El-Mofty, A., El-Mofty, A. M., Abdelal, H., and El-Hawary, M. F., Studies on mode of action of psoralen derivatives. II. Pituitary-adrenal axis control of copper metabolism and its response to psoralens. J. Invest. Dermatol. 32, 651-659 (1959). 

The crosslinking process depends on the structure of the psoralen derivative. Linear furocoumarins form crosslinks efficiently with a yield up to 50% of the overall adducts formed. 

Dimethyl l,2,4,5-tetrazine-3,6-dicarboxylate continues to be an important reagent in the inverse Diels-Alder reaction, and has been used in the synthesis of ningalin D <05JA10767>, dihydrodiol and diol epoxide of phthalazine <05T1545> and novel pyridazino-psoralen derivatives <05T4805>. 

A third ring was fused to 3-hydroxycoumarin by its reaction with benzyl-ideneacetone to give the ketone (197), which cyclized to the pyranobenzo-pyran (198) under acetylation conditions. Treatment of 3-amino-7-hydroxycoumarin with bromoacetone and cyclization of the product has given psoralen derivatives such as (199). In a new example of the addition... 

Methoxsalen is a psoralen that acts as a photosensitizer. A psoralen derivative with pigmenting properties (12 to 20 mg p.o.), methoxsalen is used to induce repigmentation in vitiligo. 

Letteron, P, V Descatoire, D. Larrey, M. Tinel, J. Geneve, and D. Pessayre (1986). Inactivation and induction of cytochrome P-450 by various psoralen derivatives in rats. J. Pharmacol. Exp. Ther. 238, 685-692. 

Tinel, M., J. Belghiti, V. Descatoire, G. Amouyal, P. Letteron, J. Geneve (1987). Inactivation of human liver cytochrome P-450 by the drug methoxsalen and other psoralen derivatives. Biochem. Pharmacol. 36, 951-955. 

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