Psoralen structure

Psoralen, or derivatives of 9-methoxy-7H-furo[3,2-g]chromen-7-one tricyclic ring structures, are used as photoreactive groups in crosslinkers, biotinylation compounds, and nucleic acid probes. Psoralens have been used for many years as photochemotherapy agents for treatment of psoriasis and vitiligo (Smith and Barker, 2006). Psoralens react when exposed to UV light... 

Cimino, C.P., Camper, H.B., Isaacs, S.T., and Hearst, J.E. (1985) Psoralens as photoactive probes of nucleic acid structure and function Organic chemistry, photochemistry, and biochemistry. Annu. Rev. Biochem. 54, 1151-1193. 

Figure 1. Structures of a linear furanocoumarin (psoralen) and an angular furanocoumarin (isopsoralen).

Only one class of benzofuran derivative, natural or synthetic, shows this property—the furocoumarins-, these are important for plant biosynthesis, since they take part in the elaboration of chlorophyll.308 13 Among linear furocoumarins, psoralene (27a) is particularly active. Angelicin (28), another fundamental furocoumarin heterocycle with an angular structure, has only about 12% of the photosensitizing activity of 27a.74-75 On the other hand, it has antibiotic activity. Furochromones have no photosensitizing properties. 

Fig. 5.16. Structures, 13C chemical shifts (in ppm) and one-bond carbon-hydrogen coupling constants (in IIz, italic types) of coumarin (left side) and the furanocoumarin psoralen (right side).

D. lindeniana furnished small quantities of psoralen and the dimeric compounds 19 and 20. The structure of the psoralen dimer 19 was established by X-ray diffraction analysis, while those of the known compounds were identified by comparison of their spectral data with those reported for the same compounds in the literature. Compound 19 was also synthesized by irradiation of psoralen (5) using a medium pressure mercury vapor lamp. This led to a mixture of isomers with the head to head, cis-syn dimer being the major product which by spectral... 

A variety of plant substances with planar, polycyclic, aromatic structures can intercalate with DNA, examples being the quinoline alkaloid camptothecin and the furanocoumarin phenolic psoralen (Table 12.1). A variety of plant-derived anthraquinones and naphthoquinones bind to DNA and it is notable that the structurally related anthraquinones mitox-antrone and adriamycin are clinically employed as anticancer drugs (Table 12.1). DNA-binding compounds that interfere with DNA repair, DNA replication and gene expression are cytotoxic and have potential as anticancer agents (see Chapter 9). 

Photoaddition of alkenes to the azathymine (227) affords the adducts (228) the structures of which were determined by -ray crystallography. Acetone-sensitized irradiation of the azauracil derivative (229) yields the cyclobutane (230). Irradiation of the uracil (231) in isotropic solvents is known to yield all four (2-1 2)-dimers in low yield especially at low concentrations. A study has shown that dimerization in smectic media affords a high yield (94X) of the trans-anti dimer (232). In frozen solutions the specificity is reversed and the CIS-anti dimer (233) is formed. The influence of a variety of media on this process was studied in detail. A theoretical treatment of the photochemical addition of alkenes to psoralens such as (234) has been published. ... 

Chemical Structure Psoralens are planar, tricyclic compounds, consisting of a furan ring fused to a coumarin moiety... 

The crystal structure of a self-complementary duplex d(CCGCTAGCGG), in which the thymine bases are cross-linked by psoralen forms a Holliday junction at the cross-link. In contrast, the psoralen cross-linked duplex d(CCGGTACCGG) forms a sequence dependent junction which is highly distorted at the thymine cross-link. The two structures contrast the drug- and sequence-dependent interactions on the structure of a Holliday junction. 

In the final chapter, Gambari et aL summarize the structure and biological effects of furocoumarins. The authors mainly focus on linear and angular psoralens. Borrowing from their laboratory experiences, they describe the interesting biological effects of such compounds on cell cycle, apoptosis and differentiation as well as their use for the treatment of j6-thalassemia. 

Fig.1 A Structure of linear psoralens. B Complex between bergapten and DNA...

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. 

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