Coumarins from psoralen

Phenolics. The phenolics of citrus represent a varied and widely studied class of compounds. They range from the lipid-soluble methoxylated coumarins and psoralens to the water-soluble glycosides of the flavanones and flavones. They include the intensely bitter naringin and the highly insoluble hesperidin. Different classes within the group have characteristic UV spectra which have been used to detect adulterations in juices and oils. 

Stanley W.L., Vannier S.H. Psoralens and substituted coumarins from expressed oil of lime. Phytochemistry, 6 585-596 (1967). 

Compositions of volatiles in different orange oils are shown in Tables 4 and 5. It is evident that most of the constituents belong to the terpene family and may be arranged into two groups, terpene hydrocarbons (terpenes and sesquiterpenes) and oxygenated terpene products (21). Aside from the volatile components, there are small amounts (2-15%) of nonvolatile residues in citrus peel oils that possess antioxidative property these include coumarins, psoralens, and polymethoxylated flavones (30-34). 

Psoralens, also known as furocoumarins, are naturally occurring or synthetic tricyclic aromatic compounds and are derived from the condensation of a coumarin nucleus with a furan ring [1-10]. Several new furocoumarins have been isolated from natural sources [10, llj. In addition, the synthetic methods for production of these molecules have been described and reviewed [10]. The synthetic methods can be organized on the basis of the key step used for the formation of the two different oxygenated rings, hi this respect, there are three possibilities (i) formation of the furan ring onto the coumarin, (ii) formation of the pyrone ring onto the benzofuran and... 

Psoralens belong to the furocoumarin class of compounds, which are derived from the fusion of a furan with a coumarin. They occur naturally in many plants, including Umes, lemons, figs, and parsnips. Two psoralens. 

On the other hand, the PPG are precursors for other complex molecules, also useful to the plants [7, 8]. From these phenylpropanoids, other phenols have been synthesized such as flavonoids, coumarins, lignans, stilbenes, psoralenes, pterocarpanes, tannins, which also act against the oxidative stress [9],... 

Many natural products contain the coumarin structure [28]. Aesculetin 15 is extracted from horse chestnuts and psoralen 16 from the Indian plant Psoralea corylifolia. Furocoumarins such as 16 are photochemically active. On UV irradiation, they induce processes in the cell which lead to an increase in skin pigmentation and inhibition of cell division. This is due to the formation of cyclobutane with the pyrimidine bases of nucleic acids. Psoralens are used in the treatment of psoriasis. 

While by definition, aroma compounds need to be volatile enough to be inhaled into the nose, flavor compounds can either be volatile or non-volatile. Volatile compounds typically have molecular weights below 300 Daltons. Nonvolatile flavor compounds can have molecular weights well over 300. Detection of non-volatiles requires the use of TLC or HPLC either alone or in tandem with an identification technique. HPLC-NMR can identify non-volatile coumarins, sterols, fatty acids and psoralens, in citrus oils, such as the substituted psoralen byakangelicol, found in lemon peel oil. Non-volatiles can act as odor fixatives, impacting the release of a perfume from the skin. Non-volatiles also serve as authentication markers that are difficult to adjust or circumvent (27). 

Coumarins are lactones with the basic structure of 1,2-benzopyrone. Biosynthetically, they are mainly originated from shikimic acid padiway, with the intermediate of cinnamic acid. By the addition of a furan ring, the furanocoumarins are resulted, which are represented by psoralen (linear) and angelicin (angular) [10]. 

FIGURE 11.83 Solid-phase synthesis of psoralen analogs. (From Song, A., Zhang, J., and Lam, K.S., Synthesis and reactions of 7-fluoro-4-methyl-6-nitro-2-oxo-27f-l-benzopyran-3-carboxylic acid a novel scaffold for combinatorial synthesis of coumarins, J. Comb. Chem., 6,112, 2004 Song, A. et al.. Solid-phase synthesis and spectral properties of 2-alkylthio-6//-pyrano[2,3-/ benzimidazole-6-ones a combinatorial approach for 2-aUcylthioimidazo coumarins, J. Comb. Chem., 6, 604, 2004 Song, A. and Lam, K.S., Parallel sohd-phase synthesis of 2-arylamino-6H-pyrano [2,3-f] benzimidazole-6-ones, Tetrahedron, 60, 8605, 2004.)... 

In some cases the coumarins formed may be further hydroxylated, methylated or substituted by isopentenyl residues. Furanocoumarins, e.g., pimpinellin, psoralen and xanthotoxin (Fig. 298), and dihydropyranocoumarins, e.g., braylin, derive from isoprenylated coumarins. The additional furane ring may be formed by the series of reactions outlined for furanoquinolines (D 8.4.2). 

Hydrodiffusion is a steam distillation method, whereby steam is fed to the plant material from the top. Steam penetrating the plant matrix condenses and forces the essential oil to diffuse to the surface. Because of gravity, oil leaves the vessel together with the condensate water from the bottom of the still. Powdering the material results in better oil yields. This technique is suitable both for superficial and subcutaneous oils. The disadvantage of this technique is the undesired extraction of coumarins, psoralens, and chlorophyll into the oil. Therefore, hydrodiffusion has not become a widely used distillation technique. 

In vitro cytotoxic activity was found against human leukemia (HL-60) cells exposed to coumarins (especially dipetaUne) and lignans (asarinin and sesamin) isolated from the root bark and fresh stems of northern prickly ash. Cytotoxic effects on human tumor cell lines were also found from crude extracts of the berries and furanocoumarins isolated therefrom (psoralen, isoimperatoin, and xanthox-toxin). The bark of southern prickly ash has shown in vitro growth inhibition of a methi-cillin-resistant strain of Staphylococcus aureus. Activity was largely attributed to the alkaloid chelerythrine, which showed activity against various other methicillin-resistant strains of the bacteria. ... 

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