Oxygen-containing coumarins

Flavones, coumarins (neoflavonoids), and other oxygen-containing compounds were found to inhibit monoamine oxidases A and B in a reversible and time-independent manner. 

Coumarin is an important natural flavoring. Explain whether the oxygen-containing ring has any aromatic character. 

In the resonance structure of coumarin shown below, the oxygen containing ring has 6 tt electrons, giving it aromatic character. 

Tetrahydrobenzopyrans, chromenes, coumarins, xanthenes, and so on are some of the most important oxygen-containing heterocyclic compounds. Several synthetic methods are available for these compounds. This part of the chapter deals with the synthesis of these heterocyclic compounds using nano-ZnO as a reusable heterogeneous catalyst. 

Halophenol derivatives are promising substrates for the synthesis of oxygen-containing heterocyclic compounds. As early as 1989, the carbony-lation of 2-iodophenol with phenyl acetylene or norbornadiene was realized. Coumarin and aurone can be prepared under the same conditions from different substrates (Scheme 2.22). 

This method has opened a very precious and useful gateway to the preparation of a series of an important oxygen-containing heterocyclic compounds, namely, coumarin and its derivatives. In this article, we try to highlight the various aspects, issues, and applications of this reaction with the hope of winning the attentions and considerations of synthetic organic chemists. 

There is also a great, number of oxygen-containing heterocyclic compounds that fluoresce. Coumarins and flavonoids are the two largest classes of oxygen heterocycles. Coumarins fluoresce more intensely under basic conditions where flavones fluoresce weakly. In 30% sulfuric acid solution, flavones fluoresce intensely and coumarins do not. 

Phenol and its derivatives are the most common substrates for the construction of oxacycles in this approach. In 2000, Fujiwara and coworkers reported a palladium-catalyzed intramolecular addition reaction of aryl alkynoates to construct coumarins in a mixture of trrfluoroacetic acid and CH2CI2 at room temperature (Scheme 3.6) [21]. This method is simple and efficient to give the desired oxygen-containing heterocycles in high yields. However, this palladium-catalyzed C-H olefination reaction is only constrained to the electron-rich aromatic compounds owing to the inherent limitation of electrophilic metalation process. 

Coumarin. The coumarin moiety is found in a number of important drugs. This is a bicyclic heterocycle containing two six-membered rings and two oxygens, one endo-cyclic, one exocyclic. Since the coumarin contains an intramolecular lactone ester, it undergoes hydrolysis to yield a carboxylic acid and a phenol. 

Both contain the carbon-oxygen skeleton of coumarin. 

The pyrilium cation 9.1, 2-pyrone 9.2, 4-pyrone 9.3, and their benzo-fused analogues the benzopyrilium cation 9.4, coumarin 9.5, chromone 9.6, are the parent structures of a series of six-membered ring heterocycles containing one oxygen atom. The impetus for research in this area comes from the enormous number of plant-derived natural products based on the benzopyrilium, coumarin, and chromone structures. 

Tables 3 and 4 contain results from a study of a series of coumarins and fiirocoumarins in, 1,2-dibromoethane, which found that the lactone carbonyl signal consistently appeared near 350 ppm more variability was seen for the single bonded oxygen, especially for the furocoumarins, typically appearing at 220 ppm [85]. Synthetic 3-aryl coumarins also exhibit 6(C=0) and 5(-0-) values near those mentioned above [86]. Recently, a study of a series of 7-substituted-4-methylcoumarins, with a wide range in electronic character of the substituents, demonstrated that the carbonyl signal is quite sensitive to substituent effects and that the NMR chemical shift is reasonably well correlated with the carbonyl oxygen AMI estimated electron density [87].

Fairly high yields of coumarins are obtainable by irradiation for 4-6 h of methoxycinnamic acids in acetonitrile-water saturated with oxygen and containing naphthalene-1,4-dinitrile. Further routes to the flavone ring system continue to appear. Flavone-3-carboxylic acids are ao ssible from fi-phenoxybenzylidenemalonic acids and either sulphuric acid or trifluoroacetic acid-trifluoroacetic anhydride. Attempts to cyclize the malonic esters were less... 

Oxidative cellular damage by reactive oxygen species such as superoxide anion, hydroperoxy and hyassociated with various human chronic diseases, e.g. cancers, inflammation, arthritis, atherosclerosis and also with the process of ageing. Claims that diet and increased intake of nutrients exhibiting antioxidative activity have a preventative effect on chronic diseases have increased in recent years. In this context, polyphenolic compounds such as tannins, flavonoids, coumarins, lignans and caffeic acid derivatives, which are abundantly contained in a large number of medicinal plants, foods and beverages, are of particular interest for human health care because of the antioxidative properties widely found in plant phenolics. The antioxidative activity of tannins has been extensively studied in various in vitro and in vivo experimental systems and summarized in reviews [96, 97]. Such activity includes the inhibition of lipid peroxidation induced by NADPH-ADP and ascorbic acid-ADP in rat liver microsomes and mitochondria, respectively... 

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