The Coumarins

4-hydroxycoumarin is a fungal metabolite, and starting chemical in the preparation of Warfarin. The phytochemical coumarin {2H-chromen-2-one} is the parent of a series of natural products. Coumarin has a vanilla-like odour, and the odour of freshly cut grass or new-mown hay will be familiar to most people. The coumarins occur naturally in essential oils such as Cinnamon, Lavender, Tonka, Lemongrass, Rose, Tagettes, and Tarragon. Perfumers have used various coumarins since the early 1800s. Nowadays you can find coumarins in the fresh handmade cosmetics sold by a company such as Lush. The name coumarin derives from the Tupi language of French Guiana where "cumaru" or "kumaru" is a flowering tree which produces black coumarin containing Tonka beans.

Coumarins can be synthesised via the Pechmann condensation. Thus phenol reacts with ethylacetoacetate in the presence of aluminium trichloride in nitrobenzene above 100°C to produce 4-methylcoumarin in high yield.

Warfarin

The author found himself the somewhat unwilling recipient of Warfarin tablets after diagnosis of AF - a medical condition which is much more prevalent than many people, including GPs realize. The idea of consuming rat poison, albeit in milligram amounts, is not very appealing! Modern rats have found some routes around the poison, either through the suspicions of an intelligent animal (they are very wary of new food items), or through natural selection.

Rattus rattus, the common black rat and its northern temperature cousin the brown rat, rattus norvegicus, are vectors for some very unpleasant diseases such as bubonic plague, typhus, Weil's disease, toxoplasmosis and trichinosis. In 1920’s North American cattle were dying from internal haemorrhaging, the poison source turned out to be from mouldy clover leaf silage. From these observations Warfarin was developed. Rat immunity to Warfarin appeared within ten years of its use as a rodenticide, and has forced the development of other "super-warfarins" such as brodifacoum, another 4-hydroxycoumarin. However this highly toxic poison is very persistent, is lipid soluble, and has been classed as an environmental pollutant.

New anticoagulants medicines have been developed, we also need to stop fighting natural selection by trying to develop even more potent super-warfarins.