Compounds Derived from Fluoroacetic Acids

Compounds Derived from Fluoroacetic Acids 11.3.1 From Monofluoroacetic Acid... 

Monhaloacetic acids are compounds derived from acetic acid with the substitution of a halogen to replace one of the hydrogens. Chloroacetate, fluoroac-etate, iodoacetate, and bromoacetate are compounds that vary in toxicity and mode of action although they are closely related. Sodium fluoroacetate was a widely used mammalian pesticide known as compound 1080. Chloroacetic acid is used as a feedstock and is manufactured in large quantities. 

Compounds Derived from Fluoroacetic Adds [5958] p. 1264 11.3.1 From Monofluoroacetic Acid [5958] p. 1264... 

The work described in this section was carried out in Cambridge during the war, and was originally submitted by us to the Ministry of Supply in communications entitled Fluoroacetates and related compounds . These communications were made available to American workers from the inception of the work. The present section is concerned mainly with a description of methyl fluoroacetate, CH2F C02Me, and of certain other derivatives of fluoroacetic acid. 

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. 

The toxicity of fluoroacetic acid and of its derivatives has played an historical decisive role at the conceptual level. Indeed, it demonstrates that a fluorinated analogue of a natural substrate could have an activity profile that is far different from that of the nonfluorinated parent compound. The toxicity of fluoroacetic acid is due to its ability to block the citric acid cycle (Krebs cycle), which is an essential process of the respiratory chain. The fluoroacetate is transformed in vivo into 2-fluorocitrate by the citrate synthase. It is generally admitted that aconitase (the enzyme that performs the following step of the Krebs cycle) is inhibited by 2-fluorocitrate the formation of aconitate through elimination of the water molecule is a priori impossible from this substrate analogue (Figure 7.1). 

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