Coumarins linear furanocoumarins

Figure 4.3 Structures of coumarins, linear furanocoumarins and angular furanocoumarins.

Phytoalexins are low molecular weight compounds produced in plants as a defense mechanism against microorganisms. They do, however, exhibit toxicity to humans and other animals in addition to microbes (30). Coumarins, glycoalkaloids, isocoumarins, isoflavonoids, linear furanocoumarins, stilbenes, and terpenes aU. fall into the category of phytoalexins (31). Because phytoalexins are natural components of plants, and because their concentration may increase as a response to production and management stimuli, it is useful to recogni2e the possible effects of phytoalexins in the human diet. 

Hadacek F, Mueller C, Werner A, Greger H, Proksch P, Analysis, isolation and insecticidal activity of linear furanocoumarins and other coumarin derivatives from Peuxedanum (Apiaceae Apioideae),/ Ecol 20 2035—2054, 1994. 

Coumarin biosynthesis involves formation of PAL and 4-coumarate CoA ligase which is light and elicitor inducible. Cells of P. crispum respond by producing the linear furanocoumarins psoralen (17), bergapten (18), and xanthotoxin (19) (Fig. 9.6), as well as other furanocoumarins (Ellis, 1988). The relative amounts of furanocoumarins in the mixture was changed by use of different fungal elicitor sources. 

There has been much interest in the biosynthesis of coumarins bearing isoprenoid-related substituents these are now considered to be mevalonate derived 338, 340, 341). In part this has stemmed from the important skin-sensitizing activity of some furanocoumarins which has been correlated with their photoreactivity towards pyrimidine bases of DNA 409). The proposal by Birch (72) that the two extra carbon atoms of the furan ring are derived by loss of three carbon atoms from an intermediate hydroxyisopropyldihydrofuranocoumarin has received considerable experimental support in recent years 152, 198, 199). Indeed, it has now been established that ( + )-marmesin (103), formed from umbelliferone (2) via 7-demethylsuberosin (86) is a key intermediate in the biosynthesis of linear furanocoumarins 105, 107,... 

Coumarins are widely distributed in the plant kingdom, especially in the families Apiaceae, Rutaceae, Leguminosae, and Compositae [30,31]. Generally, the highest level of coumarins is found in the fruits, followed by roots, stems, and leaves. In Table 1 are shown the main linear furanocoumarins present in the plant kingdom and vegetable sources. On the other hand, in Table 2 are shown the main angular furanocoumarins and their presence in different plants. 

After the separation of furanocoumarin, spectroscopic methods can be used to identify and quantify these phenolic compounds. Coumarin shows absorption bands at 274 and 311 nm, which have been attributed to the benzene and pyrone rings, respectively. Methyl substitution at C-5, C-7, or C-8 leads to a bathochromic shift of the 274 nm maximum but leaves the 311 nm maximum practically unchanged [68]. 7-Oxygenated coumarins show strong absorption bands at about 217 and 315-330 run with weak peaks or shoulders at 240-250 nm. Linear furanocoumarins show four zones of absorption at 205-225, 240-255, 260-270, and 298-316 nm. Angular furanocoumarins can readily be distinguished from linear forms since the maxima at 242-245 and 260-270 are absent [69]. 

A sensitive, specific, and rapid LC-MS method has been developed and validated for the simultaneous determination of xanthotoxin, psoralen, isoim-pinellin, and bergapten [80]. A paper by Zheng et al. [81] reported the quantitation of eleven coumarins including furocoumarins in Angelica dahurica, using HPLC-ESl-MS/MS. Yang et al. [82] developed a method for the characterization of linear furanocoumarins in Radix glehniae by LC-MS by the... 

Furanocoumarins are formed when furor ring is joined with coumarins. The plants of Rutaceae, Leguminosae and Apiaceae are rich sources of furanocoumarins. Depending upon the structure, the furanocoumarins are divided into linear and angular types. Furanocoumarin containing preparations are used externally as well as internally for treatment of leucoderma, psoriasis and skin carcinoma. 

Table 10. 13C chemical shifts of linear (F) and angular furanocoumarins (H), their 2",3 -dihydro derivatives (G and I) and of coumarins with other... 

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]. 

Effects of UV irradiation in the presence of furano-coumarins have also been studied with proteins, especially enzymes, and it is now clear that photobinding effects are not confined to nucleic acids. Both linear and angular furanocoumarins bind covalently to proteins in reactions highly dependent on structure. Enzymes are significantly inactivated, as shown in Table 1. The linear isomers appear generally to be most inhibitory, but there is great variation with the structure of both the coumarin and the protein. 

Most other reviews have classified coumarins in an arbitrary manner according to whether, for example, particular compounds were derivatives of linear or angular furanocoumarins or pyranocoumarins. In compiling the Tables included in the present review a biogenetically related approach has been adopted which is based firstly upon the number of nuclear oxygen atoms. Within each Table, the entries are presented in the following order — (i) coumarins with acyclic substituents, (ii) dihydrofuranocoumarins, (iii) furanocoumarins, (iv) dihydro-... 

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