Fluorocitric acid

The synthetic fluorocitric acid, to which reference has been made in the foregoing pages, has been prepared3 in low yield (12 per cent) by the following method from ethyl fluoroacetate 4... 

Scheme 18. Biosynthesis of (2R, 3 )-fluorocitric acid with citrate synthetase...

Fluoroacetic acid, fluorocitric acid and lethal synthesis . 1504... 

Disposition in the Body. Rapidly absorbed after ingestion or through cuts and abrasions. It is converted to fluoroacetic acid and then to fluorocitric acid. 

Disposition in the Body. Fluoroacetic acid and sodium fluoroacetate are absorbed rapidly through cuts and abrasions but less rapidly from intact skin. Sodium fluoroacetate is converted to fluorocitric acid which inhibits the citric acid cycle and leads to accumulation of citrate. 

Fluorobenzoylpropylpiperidinopiperidinecarboxamide, 904 Fluorobenzoylpropylpiperidylbenzimidazolinone, 378 Fluorobenzoylpropyltetrahydropyridylbenzimidazolinone, 576 Fluorobiphenylylpropionic acid, 631 Fluorocitric acid, 627 Fluorocytosine, 621... 

Peters, R.A., Wakelin, R.W. (1953). Fluoroacetate poisoning comparison of syntetic fluorocitric acid with the enzymi-cally synthesized fluorotricarboxylic acid. Nature 171 1111-12. 

The discovery that fluorocitric acid is a powerful inhibitor of aconitase led to a search for similar inhibitors. It was in this connection that 6-deoxy-... 

The biochemical mechanism of the toxicity of fluoroacetate in mammals was first elucidated by the notable researches of the late Sir Rudolph Peters, who showed that in liver and kidney, the compound was metabolically transformed into an even more toxic fluorocitric acid isomer, a powerful inhibitor of the tricarboxylic acid cycle. These results together with those of others, Li ecq, Bergmann,... 

Fanshier et al. (1964) have shown that the aconitase-inhibitory effect of synthetic monofluorocitrate is due to one isomer, synthesized enzymatically from fluoroacetyl coenzyme A and oxaloacetate. They separated diastereoisomers of synthetic mono-fluorocitric acid, compared the chemical and enzyme-inhibitory properties of these with enzymatically formed isomers, and found that the DL-erythro form of fluoro-citrate is the diastereoisomer which inhibits aconitase action. Infrared spectroscopy helped to characterize the DL-erythro and DL-threo isomers. 

Other cases are described in Section 13.5 under the heading Lethal examples . Thus fluoroacetic acid is transformed to fluorocitric acid which blocks the enzyme aconitase. Several amines, such as benzidine and 2-aminonaph-thalene are converted to carcinogenic hydroxylamines and polycyclic hydrocarbons such as benzopyrene are converted to carcinogenic epoxides. The liver converts carbon tetrachloride to a free radical which causes liver necrosis (Slater, 1966). 

Brandange S, Dahlman O, Morch L (1981) Highly selective re additions to a masked oxa-loacetate. Absolute configurations of fluorocitric acids. J Am Chem Soc 103 4452-4458 Pette JW (1934) Condensation of polyhydric alcohols, sugars and hydroxy-acids with aldehydes under influence of phosphorous pentoxide. Rec Trav Chim Pay-Bas et de la Belg... 

Hornfeldt, C.S., Larson, A.A., 1990. Seizures induced by fluoroacetic acid and fluorocitric acid may involve chelation of divalent cations in the spinal cord. Eur. J. Pharmacol. 179, 307-313. 

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