Clover, sweet

Coum rinic Acid Compounds. These synthetic phyUoquinone derivatives and congeners have been employed as anticoagulants since the isolation of 3,3 -methylenebis(4-hydroxy-2H-l-benzopyran-2-one) [66-76-2] (bis-4-hydroxycoumarin or dicoumarol) (1) from spoiled sweet clover in 1939. The ingestion of the latter was responsible for widespread and extensive death of bovine animals at that time. The parent compound for the synthesis of many congeners is 4-hydrocoumarin, which is synthesized from methyl salicylate by acetylation and internal cyclization. The basic stmctures of these compounds are shown in Figure 2, and their properties Hsted in Table 6 (see Coumarin). 

Dicoumarol [66-76-2] (5) was isolated from spoiled sweet clover hay. It is prepared synthetically by reaction of 4-hydroxycoumarin with formaldehyde (85). It is used in anticoagulant therapy often associated with heparin. 

Honig-harnruhr, f. diabetes mellitus. -klee, m. sweet clover, melilot. -saft, m. nectar, -silure, /. Pharm.) oxymel mellitic acid, -acheibe, /. honeycomb, -aeim, m. liquid honey. -stein, m. honeystone, mellite. -steinsilure, /. mellitic acid, honigsliss, a. honey-sweet. 

Dicoumarol is found in sweet clover and can cause hemorrhaging in cattle because of its anticoagulant action. It acts as a vitamin K antagonist and has served as a model for the development of warfarin and related anticoagulant rodenticides. 

E. S. P. Bromfield, L. R. Barran, and R. Weathcroft, Relative genetic structure of a population of Rhizobium meliloti isolated directly from soil and from nodules of alfalfa (Medicago. sativa) and sweet clover (Melilotus alba). Mol. Ecol. 4 183-188 (1995). 

Rue Sweet clover Turmeric Vitamin E Willow bark ... 

White Sweet Clover (Melllotus alba Desr.)... 

The last of the fat-soluble vitamins to be identified was vitamin K, found by Dam to be an anti-hemorrhagic factor for young chicks, distinct from vitamin C. Its structure was determined by Dam in collaboration with Karrer. Interest in the vitamin was intensified when it was discovered (Link, 1941) that dicoumarol, present in spoiled sweet clover, was the agent producing hypothrombinemia (giving prolonged blood-clotting time) in cattle. Since vitamin K is structurally similar to dicoumarol, the vitamin was presumptively implicated in thrombin formation. This has been fully substantiated by recent work on the role of vitamin K in the synthesis of prothrombin in the liver. 

Coumarin glycosides are found throughout the plant kingdom (Burrows and Tyrl, 2001). Seeds of Aesculus glabra (Ohio buckeye) contain the coumarin esculin, which is a mild neurotoxin. Sweet clovers Melilotus spp.) contain coumarins that are considered harmless unless moldy conditions exist, in which fungal activity produces the double coumarin dicoumarol. Dicoumarol is a... 

Many plants produce coumarins coumarin itself is found in sweet clover and contributes to the smell of new-mown hay. However, if sweet clover is allowed to ferment, oxidative processes initiated by the microorganisms lead to the formation of 4-hydroxycoumarin rather than coumarin. 4-Hydroxycoumarin then reacts with formaldehyde, also produced via the microbial degradative reactions, and provides dicoumarol. 

Animals fed spoiled sweet clover were prone to fatal haemorrhages. The canse was traced to the presence of dicoumarol. This compound interferes with the effects of vitamin K in blood coagulation, the blood loses its ability to clot, and minor injnries can lead to severe internal bleeding. Synthetic dicoumarol has been nsed as an oral blood anticoagnlant in the treatment of thrombosis, where the risk of blood clots becomes life threatening. It has since been snperseded by warfarin, a synthetic development based on the natnral prodnct. 

UDPG-GTases that use phenolic acids as acceptor molecules have been Isolated from several plant tissues. These include leaves of sweet clover (28), geranium (29), Oestrum euenthes (30), oak (31,... 

Rodenticides are a broad class of chemicals designed to kill mammals, particularly rats and mice. Compounds that inhibit blood clotting, anticoagulants, are commonly used to control rat populations. One of the first was warfarin, which is related to the plant-derived coumadin (from spoiled sweet clover). In the 1950s rats developed resistance to warfarin, which prompted the development of more potent anticoagulants. Other rodenticides include fluoroacetic acid and zinc phosphide (very toxic) and thiourea-based compounds. The primary alternative to using rodenticides is trapping. 

Coumarins are also synthesized by a variety of plant species. Medically, the most significant coumarins are dicoumarol and its derivative, warfarin. Dicoumarol was initially discovered as the active substance in mouldy sweet clover hay, which could induce haemorrhagic disease in cattle. Dicoumarol and warfarin are now used clinically as anticoagulants, as discussed in Chapter 9. 

The only major side-effect of these oral anticoagulants is prolonged bleeding, thus the dosage levels are chosen with care. Dicoumarol was first isolated from spoiled sweet clover hay, as the agent which promoted haemorrhage disease in cattle. Both dicoumarol and warfarin have also been utilized (at high doses) as rat poisons. 

Bishydroxycoumarin (dicoumarol) is a natural occurring anticoagulant found in sweet clover. A number of coumarin derivatives have been synthesized as anticoagulants, warfarin, phenprocoumon and acenocoumarol being most frequently used. The nonpolar carbon substituent at the 3 position required for activity is asymmetrical. The enantiomers differ in both pharmacokinetic and pharmacodynamic properties. The coumarins are marketed as racemic mixtures. 

R = CH2CH2CH(CH3)2, C12H16O3, M, 208.26, bp2 151-152X, df 1.0535, nf 1.5065, has been found in a number of fruit aromas. It is a colorless liquid with a sweet, clover-like odor and is used in perfumery for floral and herbal notes, particularly in soap perfumes. 

Coumarin was first isolated by Vogel in 1820 by extraction from tonka beans (Dipteryx odorata). It was subsequently identified in a large number of plants belonging to many different families. Its better known occurrences are in sweet clover (Melilotus alba and M. officinalis), sweet woodruff (Asperula odorata), vanilla leaf (Trilisa odoratissima), vanilla beans (Vanillaplanifolia), cassia (Cinnamorum cassia), lavender (Lavendula officinalis) and balsam of Peru (Myroxylon pereirae) (Perone, 1972 Maries et al, 1987 Boisde Meuly, 1993 Budavari, 1998). 

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). 

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