Coumarin

|Section2= |Section3= }} Coumarin (2H-chromen-2-one) is a chemical compound (specifically, a benzopyrone) found in many plants, notably in high concentration in the tonka bean (Dipteryx odorata), vanilla grass (Anthoxanthum odoratum), woodruff (Galium odoratum), mullein (Verbascum spp.), and sweet grass (Hierochloe odorata). The name comes from a French word, coumarou, for the tonka bean. It has a sweet scent, readily recognised as the scent of newly-mown hay, and has been used in perfumes since 1882.

Although coumarin has no anticoagulant activity, it is transformed to the natural anticoagulant dicoumarol by a number of species of fungi. This proceeds through production of 4-hydroxycoumarin, then further (in the presence of naturally occurring formaldehyde) into the actual anticoagulant dicoumarol, a fermentation product and mycotoxin.

Coumarin is used in the pharmaceutical industry as a precursor molecule in the synthesis of a number of synthetic anticoagulant pharmaceuticals similar to dicoumarol, notably warfarin (which has a common and confusing brand name Coumadin) and some even more potent rodenticides that work by the same anticoagulant mechanism. See 4-hydroxycoumarin for a discussion and listing of this class of drugs.

Coumarin has clinical medical value by itself, as an edema modifier. Coumarin and other benzopyrones, such as 5,6 benzopyrone, 1,2 benzopyrone, diosmin and others are known to stimulate macrophages to degrade extracellular albumen, allowing faster resorption of edematous fluids.

Coumarin is also used as a gain medium in some dye lasers.

Synthesis

The biosynthesis of coumarin in plants is via hydroxylation, glycolysis and cyclization of cinnamic acid. Coumarin can be prepared in a laboratory in a Perkin reaction between salicylaldehyde and acetic anhydride.

The Pechmann condensation provides another synthesis of coumarin and its derivatives.

Biological function

Coumarin has appetite-suppressing properties, suggesting one reason for its widespread occurrence in plants, especially grasses and clovers, is because of its effect of reducing the impact of grazing animals. Although the compound has a pleasant odor, it has a bitter taste, and animals will avoid it, if possible.

Derivatives

Coumarin and its derivatives are all considered phenylpropanoids.

Some naturally occurring coumarin derivatives include umbelliferone (7-hydroxycoumarin), aesculetin (6,7-dihydroxycoumarin), herniarin (7-methoxycoumarin), psoralen and imperatorin.

4-phenylcoumarin is the backbone of the neoflavones, a type of neoflavonoids.

Medical use

Coumarin has been used in the treatment of lymphedema.

Toxicity and use in foods, beverages, tobacco, and cosmetics

Coumarin is moderately toxic to the liver and kidneys, with an LD₅₀ of 275 mg/kg—low compared to related compounds. Although only somewhat dangerous to humans, coumarin is a potent rodenticide: rats and other rodents largely metabolize it to 3,4-coumarin epoxide, a toxic compound that can cause internal hemorrhage and death. Humans largely metabolize it to 7-hydroxycoumarin, a compound of lower toxicity. The German Federal Institute for Risk Assessment has established a tolerable daily intake of 0.1 mg coumarin per kg body weight, but also advises that, [if] this level is exceeded for a short time only, there is no threat to health. For example, a person weighing 135 lbs or about 61 kg would have a TDI of approximately 6.1 mg of coumarin.

European health agencies have warned against consuming high amounts of cassia bark, one of the four species of cinnamon, because of its coumarin content. According to the German Federal Institute for Risk Assessment, 1 kg of (cassia) cinnamon powder contains approximately 2100 to 4400 mg of coumarin. Powdered Cassia Cinnamon weighs 0.56 g/cc; therefore, 1 kg of Cassia Cinnamon powder is equal to 362.29 teaspoons (1000 g divided by 0.56 g/cc multiplied by 0.20288 tsp/cc). This means 1 teaspoon of cinnamon powder contains 5.8 to 12.1 mg of coumarin, which may be above the Tolerable Daily Intake for smaller individuals. Coumarin was banned as an adulterant in cigarettes by tobacco companies in 1997, but due to the lack of reporting requirements to the US Department of Health and Human Services it was still being used as a flavoring additive in pipe tobacco. Coumarin is currently listed by the United States Food and Drug Administration (FDA) among "Substances Generally Prohibited From Direct Addition or Use as Human Food", according to 21 CFR 189.130, but some natural additives containing coumarin (such as Sweet Woodruff) are allowed "in alcoholic beverages only" (21 CFR 172.510). In Europe, such beverages are very popular, for example Maiwein (white wine with woodruff) and Żubrówka (vodka flavoured with bison grass).

Coumarin should be avoided by people with perfume allergy.

Related compounds and derivatives

Compounds derived from coumarin are also called "coumarins". Compounds within this coumarin family include: brodifacoum bromadiolone coumafuryl difenacoum

auraptene

ensaculin

phenprocoumon (Marcoumar)

Scopoletin can be isolated from the bark of Shorea pinanga

warfarin

Many of the above compounds (specifically the 4-hydroxycoumarins) are used as anticoagulant drugs and/or as rodenticides which work by the anticoagulant mechanism.

Use as pesticides

Coumadins, dicoumerol derivatives of coumarin, are potent rodenticides because they block the synthesis of vitamin K, especially in rodents, giving it strong anticoagulatory and rodenticidal properties. Death occurs after a period of between several days to two weeks, usually from internal hemorrhaging.

Vitamin K is a true antidote for poisoning by coumadins such as bromadiolone. Treatment usually comprises a large dose of vitamin K given intravenously immediately, followed by doses in pill form for a period of at least two weeks, though usually three to four, afterwards. If caught early, prognosis is good, even when large amounts are ingested. Transfusion with fresh frozen plasma to provide clotting factors also provides time for vitamin K to reverse enzyme poisoning in the liver and allow new clotting factors to be synthesized there.

See also

Żubrówka

References

External links

More info about coumarin

Coumarin in tobacco

More info about Coumane(TM)

Coumarin as an ingredient of perfume.

Category:Types of phenylpropanoids Category:Fluorescent dyes Category:Fuel dyes Category:Laser gain media Category:Coumarins