Fluorofatty acid

Several F-labeled fatty acid derivatives have been successfully prepared and evaluated as potential FAO assessing tracers [19-24]. Methyl-branched-chain (w- F-fluorofatty acids, such as 3-methyl-(3-MFHA) and 5-methyl-17-[ F]fluoro-heptadecanoic acid (5-MFHA), have been reported [23]. In a comparative study, it was found that rw-[ F]fluoropalmitic acid (FPA) exhibits the highest myocardial uptake, followed by 5-MFHA and 3-MFHA. FPA possesses the fastest myocardial washout rate, and 3-MFHA the slowest. In lipid analysis studies, 5-MFHA... 

M.M. Goodman, F.F. Knapp Jr, Radiochemical synthesis of [ F]-3-methyl-branched omega fluorofatty acids, J. Label. Compd. Radiopharm. 26 (1989) 233-235. 

T. Takahashi, S. Nishimura, T. Ido, K. Ishiwata, R. Iwata, Biological evaluation of 5-methyl-branched-chain omega-[ F]-fluorofatty acid A potential myocardial imaging tracer for positron emission tomography, Nucl. Med. Biol. 23 (1996) 303-308. 

Monofluoroacetic acid (fluoroacetate, figure 7,39) is a compound found naturally in certain South African plants, and which causes severe toxicity in animals eating such plants. The compound has also been used as a rodenticide. The toxicity of fluoroacetate was one of the first to be studied at a basic biochemical level, and Peters coined the term lethal synthesis to describe this biochemical lesion. Fluoroacetate does not cause direct tissue damage and is not intrinsically toxic but requires metabolism to fluoroacetyl CoA (figure 7,39). Other fluorinated compounds which are metabolized to fluoroacetyl CoA therefore produce the same toxic effects. For instance, compounds such as fluoroethanol and fluorofatty acids with even numbers of carbon atoms may undergo /1-oxidation to yield fluoroacetyl CoA. 

At that time, the techniques for quantitative microanalysis of organic fluorides were quite inadequate until an outstanding complexometric method was devised in Belcher s laboratory (13). It appeared from extensive surveys that fluorofatty acids in fact were widespread in trace quantities in many species of green plants. 

In the 1950 s further exploration of this route, modifying solvent, blocking groups and conditions, led to 6F-galactose and a number of monosaccharides F-substituted in the extra cyclic position. Unlike the even-numbered 0)-fluorofatty acids, none of these o)-substituted sugars were metabolised to fluoroacetate and exhibited little or no toxicity. 

In the cellular metabolism F. reacts with citrate synthase to form (2R,3R)-2-fluorocitrate (QH7FO7, Mr 210.12), which inhibits transport of citrate through mitochondrial membranes. The lethal synthesis of fluorocitrate, however, only contributes to a small extent to the toxic activity. D. toxicarium stores F. in its extremely toxic seeds in the form of cu-fluorofatty acids, principally co-fluorooleic acid (C,gH33F02, Mr 300.46). Fluoroacetyl-CoA functions here as a starter unit. The biosynthesis of F. from fluoride ions has not been elucidated. 

A number of (o-fluorofatty acids are known to occur in seeds of species of the genus Dichapetalum, especially in Di-... 

Varying degrees of vitro antifungal activity have been claimed for a variety of chemical types. Among these are substituted 8-hydroxyquino-lines,J 2 acetylenic con5>oun, 3 2-fluorofatty acids,alkyl phenyl sulfides,aryl thiocyanates,substituted phenylhydrazines and phenyl-pyrazolones methyl-5-(3,3-dimethyl-l-triazeno)imidazole- -carboxylate p-hydroxypropiophenone,50 substituted benzimidazoles,51 2,U-bis(arylamino)-5-methylpyrimidines52 and isothiocyanates.53... 

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