Dicoumarol formation

Davies, E. G. and W. M. Ashton, Coumarin and related compounds of Anthoxanthum puelii and Melilotus alba and dicoumarol formation in spoiled sweet vernal and sweet clover hay, J. Sci. Food Agric., 15, 733-738 (1964). 

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. 

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. 

Synthetic dihydro form (KH2) coenzyme for "y-carboxyglutamic acid formation on procagulant factors II, VII, IX, X, anticoagulant proteins C S, matrix Gla protein osteocalcin Synthetic cf. Dicoumarol, Vitamins K,K2 K3... 

Dicoumarol is found in spoiled sweet clover warfarin is used as a rat poison. Similar antagonists may be used clinically to reduce the probability of blood clotting in patients with a tendency to thrombus formation. Several other clotting factors also contain g-carboxyglutamate and they, too, will be affected by vitamin K antagonists. 

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