Plant Dichapetalum

Fluoroacetic acid [144-49-OJ, FCH2COOH, is noted for its high, toxicity to animals, including humans. It is sold in the form of its sodium salt as a rodenticide and general mammalian pest control agent. The acid has mp, 33°C bp, 165°C heat of combustion, —715.8 kJ/mol( —171.08 kcal/mol) (1) enthalpy of vaporization, 83.89 kJ /mol (20.05 kcal/mol) (2). Some thermodynamic and transport properties of its aqueous solutions have been pubHshed (3), as has the molecular stmcture of the acid as deterrnined by microwave spectroscopy (4). Although first prepared in 1896 (5), its unusual toxicity was not pubhshed until 50 years later (6). The acid is the toxic constituent of a South African plant Dichapetalum i mosum better known as gifirlaar (7). At least 24 other poisonous plant species are known to contain it (8). 

Biotransformation, especially phase I metabolic reactions, cannot be assumed to be synonymous with detoxification because some drugs (although a minority) and xenobiotics are converted to potentially toxic metabolites (e.g. parathion, fluorine-containing volatile anaesthetics) or chemically reactive intermediates that produce toxicity (e.g. paracetamol in cats). The term lethal synthesis refers to the biochemical process whereby a non-toxic substance is metabolically converted to a toxic form. The poisonous plant Dichapetalum cymosum contains monofluoroacetate which, following gastrointestinal absorption, enters the tricarboxylic acid (Krebs) cycle in which it becomes converted to monofluorocitrate. The latter compound causes toxicity in animals due to irreversible inhibition of the enzyme aconitase. The selective toxicity of flucytosine for susceptible yeasts (Cryptococcus neoformans, Candida spp.) is attributable to its conversion (deamination) to 5-fluorouracil, which is incorporated into messenger RNA. 

Monofluoroacetate, a toxin from the poison leaf plant Dichapetalum cymosum, was isolated and analyzed on a specialty organic acid analysis column (2 = 210nm) using an aqueous 20 mM H3PO4 mobile phase [1580]. This compound waS well separated from formic, acetic, and propionic acids. Peak shapes were excellent and elution was complete in 35 min. Linearity was achieved over the range 25-... 

Fluoroacetic acid occurs in a South African plant Dichapetalum and has killed many cattle in that country. The toxic action of fluoroacetic acid does not depend on any chemical reactivity on the part of fluorine, but on the small size of the fluorine atom (Table 9.1) (Bartlett and Barron, 1947). 

As might be expected, bacteria have been isolated from the plants that prodnce flnoroacetate, and these include an unidentified Pseudomonas sp. (Goldman 1965), a strain of Burkholderia Pseudomonas) cepacia from Dichapetalum cymosum (Meyer et al. 1990), and a strain of Morax-ella sp. (Kawasaki et al. 1981). In addition, fluoroacetate is an unusual product of microbial metabolism ... 

It is interesting to note that the toxic sodium fluoroacetate (above, p. 11) occurs in the poisonous South African plant gifblaar (Dichapetalum cymosum, PI. I). It has recently been shown that sodium fluoroacetate is a highly effective systemic insecticide, but it is difficult to say exactly how this substance will be applied on a large scale.6 There are many other insecticides containing fluorine and phosphorus, and special precautions must be taken when handling these toxic compounds. 

Fluorine can be acccumulated and metabolised by a number of plant species, in particular the African Dichapetalum species and the Australian Acacia georginae. These plants all contain fluoroacetate which may be up to 50 mg kg-1 dry weight. High concentrations of up to 1 % F in dry plant tissues have been found in plants growing on fluorite-rich spoil (Cooke et al., 1976) as compared with normal values of around 30 mg kg 1 (Kabata-Pendias and Pendias, 1984). 

Fluoroacetic acid is the toxic principle of the South African plant gifblaar, Dichapetalum cymosum = Chailletia cymosa) (Dichapetalaceae). Crystals. M.p. 33° to 35°. B.p. 165° to 168°. Soluble in water and ethanol practically insoluble in most common organic solvents. 

Fluoroacetic acid has been identifled as the toxic component of the South African plant gijblaar (Dichapetalum cymosum) [34]. Its mechanism of action is based on inhibition of the citric acid cycle, the main source of metabolic energy in all animals [35]. In this cyde, fluoroacetate can replace acetate as a substrate of aconi-tase, an enzyme complex which usually forms dtrate by addition of acetate to a-oxoglutarate. The resulting fluorocitrate is binds tightly to the enzyme, but cannot be further converted to ds-aconitate and isocitrate [36], thus inhibiting aconitase. 

Fluoroacetate (3), the sodium salt of monofluoroacetic acid, is also a substance of vegetable origin, reported to poison sheep and cattle repeatedly. It is the toxic substance of a South African plant called gifblaar (Dichapetalum cymostm) and of the Australian plant Acacia georginae (Marais, 1944). The compound is readily soluble in water and is very toxic. Its acute oral lDj for rats is 0.2-2 mg/kg. The compound is converted via the citrate cycle into fluorocitrate and this blocks the citrate cycle. 

Douglas fir, Pseudotsuga menziesii, 183, 255 Eluoroacetate accumulator plants Acacia georginae, 783, 795 Dichapetalum spp., 783, 795 Giffblaar, Dichapetalum cymosium, 783, 795 Oxylobium spp., 798 Palicourea spp., 783... 

C2H3FO2, Mr 78.04, needles, mp. 35 °C, bp. 165 °C. The highly toxic F. was first discovered in 1943 as the toxic principle of the South African plant Dichape-talum cymosum (Dichapetalaceae) which is responsible for the death of a large number of cattle. Since then F. has been detected in many other plants, in particular in African Dichapetalum species (D. braunii... 

Huoroacetic add CHjF-COOH, a very poisonous carboxylic acid which is converted in the tricarboxylic acid cycle to fluorocitrate, a strong inhibitor of aconitase. The Thcarboxylic add cycle (see) therefore ceases to operate, with lethal results. Free F.a. occurs in the leaves of Dichapetalum cymosum, a poisonous African plant which is reponsible for cattle poisoning in South Africa. It is aira present in other plants to which it confers toxidty. [L.P. Miller and EFIemion Phytochemistry 3 (1973) 1- j nuorodtric add see Fluoroacetic add. 

Fluoroacetic acid was identified as the toxic principle of Dichapetalum cymosum, which is one of the most poisonous plants growing in South Africa (70). This acid was subsequently found in many plants belonging to several families in Africa and Australia. The seeds of D, toxicarium contain, besides a small amount of fluoroacetic acid, cofluorooleic acid as the major toxic compound (91). The presence of cu-fluoropalmitic, o>fluorocapric, and cu-fluoromyristic acids have also been reported (122). Biosynthesis of fluoroacetic acid has been proposed to occur by a nucleophilic incorporation of a fluoride ion into a C3 unit linked to... 

Esters, V, Karangwa, C., Tits, M., et al., 2013. Unusual amino adds and monofluoroacetate from Dichapetalum michelsonii (Umutambasha), a toxic plant from Rwanda. Planta Med. 79 (5), 334-337. 

Fluoroacetate. Fluoroacetate 1 is the most ubiquitous fluorine-containing natural product and has been identified in over 30 plants, principally species from Africa and Australia, and also as a secondary metabolite in the bacteria Streptomyces cattleya (see below). The compoimd was first identified by Marais (4) in South Africa as the toxic principle in plants of Dichapetalum cymosum (gifblaar). The young leaves of this plant are particularly toxic in the spring when levels of fluoroacetate of up to... 

---