Coumarin derivatives, chemical structures

Fig. 6.4. Chemical structures of coumarin and some of its fluorescent derivatives.

Table 5.37. Structures and 13C Chemical Shifts (<5C in ppm) of Natural Coumarin Derivatives [635],...

Fig. 7 Chemical structures and calculated logP values of 3-formylchromone and coumarin derivatives (FC1-16)...

Optical brighteners are usually derivatives of coumarin, stilbene, dis-tyrylbipheny, and bis(benzoxazole). Examples of chemical structures of some important optical brighteners are given ... 

The contradictory observations on the toxicity of coumarin stimulated our research into closely related coumarin derivatives in biochemical-pharmacological studies. Considering the limited information available in the various reviews on the biological properties of these compounds, the main emphasis in this paper will be placed on this aspect. It has been considered important to discuss the chemical structure-biological activity relationship of simple coumarins, coumarin anticoagulants, light sensitisers, aflatoxins, and related isocoumarin... 

The basic skeleton of isoprenoids may be modified by the introduction of a wide variety of chemical groups, by isomerization, shift of double bonds, methyl groups, etc. Hence a bewildering number of chemical structures arises. In addition compounds derived from other biogenic pathways may contain isoprene residues. For instance the K vitamins (D 8.1), ubiquinones (D 8.3), chlorophylls (D 10.1), plastoquinones, and tocopherylquinones (D 22.4) have isoprenoid side chains with up to ten isoprene units. Polyketides (D 3.3), alkaloids (D 8.4.2), and coumarins (D 22.2.2) may be substituted by dimethylallyl groups. The terpene residues are attached to nucleophilic sites, such as active methylene groups and phenolic oxygen atoms. 

The isoprene-derived molecule whose structure is shown here is known alternately as Coumarin and warfarin. By the former name, it is a widely prescribed anticoagulant. By the latter name, it is a component of rodent poisons. How can the same chemical species be used for such disparate purposes The key to both uses lies in its ability to act as an antagonist of vitamin K in the body. 

Several reports describing the 170 NMR of pyrans and derivatives have appeared, including a study in which the natural abundance 170 NMR data for lactones such as pyranone were collected and the relationships between 170 chemical shifts and structure were discussed of <1989H(29)301>. It is possible to distinguish between polyfunctionalized coumarins and chromones by 170 NMR <1993CPB211>. 

Corroborative evidence for the structures of various coumarinolignans, deduced almost exclusively from spectroscopic evidence, has been provided by their appropriate synthesis. The synthesis of this group of natural products has been achieved mainly through oxidation (chemical or enzymatic) of appropriate coumarin and phenylpropanoid derivatives, although other methods are also known. 

The simple coumarin nucleus (Fig 7.3), which is derived by lactone formation of an ortho-hydroxy-czs cinnamic acid, is a common metabolite in higher plants and is often found in glycosidic form. Coumarins are common in Api-aceae, in certain genera of Fabaceae (e.g. Dipteryx odorata, Melilotus officinalis), Poaceae (e.g. Anthoxanthum odoratum) and Rubiaceae (e.g. Galium odoratum). However, proliferation of coumarins to the status of major chemical markers occurs in only a few cases, most notably, but not exclusively, in the Api-aceae (subfamily Apioideae) and in the Rutaceae (Gray and Waterman, 1978 Murray et al., 1982). In these cases, the coumarin nucleus has almost invariably been embellished by the addition of a prenyl unit leading to furocoumarin (Fig 7.3) and pyranocoumarin structures. 

It has been noted that the chemical diversity of plant phenolics is as vast as the plant diversity itself. Most plant phenolics are derived directly from the shikimic acid (simple benzoic acids), shikimate (phenylpropanoid) pathway, or a combination of shikimate and acetate (phenylpropanoid-acetate) pathways. Products of each of these pathways undergo additional structural elaborations that result in a vast array of plant phenolics such as simple benzoic acid and ciimamic acid derivatives, monolig-nols, lignans and lignin, phenylpropenes, coumarins, stilbenes, flavonoids, anthocyanidins, and isollavonoids. 

The third chapter, Quantitative Structure-Cytotoxicity Relationship of Bioactive Heterocycles by the Semi-empirical Molecular Orbital Method with the Concept of Absolute Hardness by Mariko Ishihara, Hiroshi Sakagami, Masami Kawase, and Noboru Motohashi, presents the relationship between the cytotoxicity (defined as 50% cytotoxic concentration) of heterocycles such as phenoxazine, 5-trifluoromethyloxazoles, O-heterocycles such as 3-formylchromone and coumarins, and vitamin K2 derivatives against some tumor cell lines and 15 chemical descriptors. The results suggest the importance of selecting the most appropriate descriptors for each cell type and compound. The review is of interest as it represents the relationship of the molecular structures with the cytotoxic activity of these heterocycles. 

Abstract Construction of chemical libraries is a useful approach to the discovery of better fluorescent materials, and several types, such as styryl dyes and cyanine dyes, have been reported. In this chapter, we focus on construction of a library of chemicals having a coumarin skeleton as the core structure. Coumarin and its derivatives are key structures in various bioactive or fluorescent molecules, and their fluorescence properties are dependent on the precise structure, including the positions of substituents. 

The parent compound, coumarin, has been found to cause chromosome breakage in animal tissues [207, 336]. The mechanism of this action and the effect on chromosomes by chemical mutagens has not yet been elucidated [337], There is hardly any structural relationship of action between these compounds. Good chromosome breakers of mammalian cells or plants include bromouracil, caffein and derivatives, alkylating agents, phenols, quinones, colchicine, methyl-phenyl-nitrosamine [337-343]. However, there is another plant product, podophyl-lotoxin, related to coumarin, which also causes chemical mutagenesis [338, 344]. 

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