Coumarins natural products

Hardt, TJ. Ritschel, W.A. (1983) Dose-related pharmacokinetics of coumarin, 7-hydroxy-coumarin and 7-hydroxycoumarin glucuronide upon intraperitoneal administration of coumarin and 7-hydroxycoumarin in the rat. Arzneim.-Forsch., 33, 1442-1446 Haworth, S., Lawlor, T, Mortelmans, K., Speck, W. Zeiger, E. (1983) Salmonella mutagenicity test results for 250 chemicals. Environ. Mutagen., 5 (Suppl. 1), 3-142 Hazleton, L.W., Tusing, T.W., Zeitlin, B.R., Thiessen, R., Jr Murer, H.K. (1956) Toxicity of coumarin. J. Pharmacol, exp. Ther., 118, 348-358 Hoult, J. Payd, M. (1996) Pharmacological and biochemical actions of simple coumarins natural products with therapeutic potential. Gen. Pharmacol., 27, 713-722... 

Hoult JR, Paya M. Pharmacological and biochemical actions of simple coumarins natural products with therapeutic potential. Gen Pharmacol 1996 27 713-22. 

In a similar manner, reaction of enol ether 2-787, hydroxycoumarin (2-781), and a-diketone 2-786 led to the cycloadduct 2-788 in 79% yield using Yb(OTf)3 as catalyst (Scheme 2.174). 2-788 could be transformed into the natural product preethulia coumarin (2-789). 

Shikimates, which include phenylalanine, tyrosine, tryptophan, and their derivatives, are represented by many aromatic natural products, including hydroquinones found inbrownalgae such as Sargassum (Segawaand Shirahama 1987). Flavonoids are a structural class of shikimates found in plants, including isoflavonoids or neo-flavonoids, as is the y-pyrone (coumarin) core structure (Knaggs 2003). 

A review of Claisen rearrangements in aqueous solution has appeared. The synthesis of natural products utilizing tandem Diels-Alder additions with sigmatropic rearrangement processes has been reviewed, and a brief review of the regioselective synthesis of coumarins, quinolones and thiocoumarins with 3,4-fused pyran or furan ring systems by the Claisen rearrangement has been presented. ... 

To design a supercritical fluid extraction process for the separation of bioactive substances from natural products, a quantitative knowledge of phase equilibria between target biosolutes and solvent is necessary. The solubility of bioactive coumarin and its various derivatives (i.e., hydroxy-, methyl-, and methoxy-derivatives) in SCCO2 were measured at 308.15-328.15 K and 10-30 MPa. Also, the pure physical properties such as normal boiling point, critical constants, acentric factor, molar volume, and standard vapor pressure for coumarin and its derivatives were estimated. By this estimated information, the measured solubilities were quantitatively correlated by an approximate lattice equation of state (Yoo et al., 1997). 

Coumarin is a natural product found at high levels in some essential oils, particularly ciimamon leaf oil (40 600 ppm (mg/kg)), ciimamon bark oil (7000 ppm), other types of cinnamon (900 ppm), cassia leaf oil (17 000-87 300 ppm), peppermint oil (20 ppm), lavender oil, woodruff and sweet clover as well as in green tea (0.2-1.7 ppm), fruits such as bilberry and cloudberry and other foods such as chicory root (Boisde Meuly, 1993 TNO, 1996 Lake, 1999). It is also found in Mexican vanilla extracts (Sullivan, 1981 Maries etal, 1987). 

Coumarin is a natural product occurring in the essential oils of a large number of plants, such as cinnamon, cassia, lavender and woodruff. It is used for its fragrance in many personal care products (perfumes, deodorants, soaps) and in tobacco, in household and industrial products to mask unpleasant odours and, in some countries, as a flavouring agent in food and beverages. It has also been used to treat several medical conditions. Exposure to coumarin may occur from its production, its natural presence in many plants and essential oils, and its several industrial, medical and consumer uses. 

A substantial listing of UV spectra of coumarins is available (71PMH(3)190) and examples of the identification of natural products based on the coumarin ring system by UV analysis, amongst other methods, have been reported (58JA3686,69MI22202). 

Phloroglucinol (42) is a colorless and odorless solid which is only sparingly soluble in cold water (82). It was discovered in 1855 in the hydrolysis products of the glucoside phloretin, which was obtained from the bark of fruit trees. Phloroglucinol occurs in many other natural products in the form of derivatives such as flavones, catechins, coumarin derivatives, anthocyanidins, xanthins, and glucosides. 

Matern U, LUer P and Kreusch D (1999) Biosynthesis of coumarins. Comprehensive Natural Products Chemistry, Vol 1. Elsevier, Amsterdam, pp 623-637. 

Several natural products contain substances that have coumarin, salicylate, or exhibit antiplatelet properties. Therefore, a theoretical risk for potentiation of the pharmacological activity of warfarin exists when these herbs are taken with warfarin. Herbs thought to contain coumarin or coumarin derivatives include the following ... 

The use of coumarin in Diels-Alder reactions is, by comparison to pyran-2-ones, still largely unexplored. This is likely due to the low reactivity of the double bond at positions 3 and 4. Diels-Alder reactions with 3-substituted coumarins are rare, despite the potential to synthesize tetrahydro-6//-benzo[c]chromen-6-ones, important precursors to functionalized biphenyls and several natural products. Electron-withdrawing substitution at C-3 does not serve to efficiently activate the dienophilic system thus, it has been found that high temperatures and pressures are necessary to effect the reaction (e.g., Equation 25) <2006JOC70>. 

Diels-Alder homo-dimerizations of hydroxybutenyl and pentadienyl coumarins have been explored in the context of the plant-derived natural products phebalin, thamnosin, and toddasin <2000TL9909>. The Diels-Alder union of two identical coumarin units occurs under thermal, Lewis acid, or mineral acid conditions (e.g., 294 —> 295 Scheme 38). 

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. 

Coumarin 9.5 is itself a natural product which been found in over sixty species of plants. 

The continuous search for germination inductors to control parasitic weeds has led to testing a great variety of natural products. Some positive results have been obtained for Striga with compounds such as the coumarin scopoletin (11), the... 

The direct irradiation of the parent coumarin in the presence of alkenes results only in an inefficient photodimerization and [2 + 2]-photocycloaddition. Lewis acid coordination appears to increase the singlet state lifetime, and leads to improved yields in the stereospecific [2 + 2]-photocycloaddition [95]. Alternatively, triplet sensitization can be employed to facilitate a [2 + 2]-photocycloaddition. Yields of intramolecular [2 + 2]-photocycloadditions remain, however, even with electron-rich alkenes in the medium range at best. The preference for HT addition and for formation of the exo-product is in line with mechanistic considerations discussed earlier for other triplet [2 + 2]-photocycloadditions [96, 97]. Substituted coumarins were found to react more efficiently than the parent compound, even under conditions of direct irradiation. 3-Substituted coumarins, for example, 3-methoxy-carbonylcoumarin [98], are most useful and have been exploited extensively. The reaction of 3-ethoxycarbonylcoumarin (100) with 3-methyl-l-butene yielded cleanly the cyclobutane 101 (Scheme 6.36) with a pronounced preference for the exo-product (d.r. = 91/9). Product 101 underwent a ring-opening/ring-closure sequence upon treatment with dimethylsulfoxonium methylide to generate a tetrahydrodibenzofur-an, which was further converted into the natural product ( )-linderol A (102) [99]. 

At the time when Shalimar was made it was customary to use a high proportion of the alcoholic tinctures made from natural products, rather than the concentrated absolutes and resins. These would have included such products as vanilla, benzoin, and tonka to give naturalness to the ethyl vanillin and coumarin, as well as tinctures of civet, castoreum, ambergris, and musk. Such products retain more of the most volatile components of the starting material, giving a wonderful quality and life to the finished product. 

Many natural products are formed from the shikimate pathway. Most can be recognized by the aromatic ring joined to a three-carbon atom side chain. Two simple examples are coumarin, responsible for the smell of mown grass and hay, and umbelliferone, which occurs in many plants and is used in suntan oils as it absorbs UV light strongly. These compounds have the same aryl-C3 structure as Phe and Tyr, but they have an extra oxygen atom attached to the benzene ring and an alkene in the C3 side chain. 

With nearly 20 years of experience on plant-derived natural products, NPRL has identified numerous active anti-HIV compounds including polycyclic diones, saponins, alkaloids, triterpenes, polyphenols, flavonoids and coumarins. Triterpenes have diverse structures and pharmacological activities. 

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