Monofluoro Aliphatic Compounds

Pattison, F. L. M.; Peters, R. A.

doi:10.1007/978-3-662-25198-0_8

Cited by 14 publications

(13 citation statements)

References 161 publications

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“…For the same reason, its derivatives and homologs having an even number of carbon atoms in their chains and a single fluorine atom in the w-positions must also be handled with proper care [2].…”

Section: Handling Of Fluorine Hydrogen Fluoride and Fluorine Compoundsmentioning

confidence: 99%

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Organic Fluorine Chemistry

Hudlický

1971

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Section: Handling Of Fluorine Hydrogen Fluoride and Fluorine Compoundsmentioning

confidence: 99%

“…However, one exception is worth quoting: Conversion of I-methoxybicyclo (2,2,2)octane to I-fluorobicyclo (2,2,2)octane by acetyl fluoride in the presence of boron trifluoride (134) [Equation (78)]. …”

Section: Cleavage Of Ethers and Epoxidesmentioning

confidence: 99%

Organic Fluorine Chemistry

Hudlický

1971

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“…FAC is known to be a highly cardiotoxic and neurotoxic poison. Indeed, it also enters the Krebs cycle, is then transformed into fluorocitrate (FC) which inhibits citrate metabolism resulting in accumulation of intracellular citrate (Pattison & Peters, 1966) (Figure 1). …”

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confidence: 99%

Cardiotoxicity of commercial 5-fluorouracil vials stems from the alkaline hydrolysis of this drug

Lemaire

Mc²,

Forni³

et al. 1992

Br J Cancer

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Summary The cardiotoxicity of 5-fluorouracil (FU) was attributed to impurities present in the injected vials. One of these impurities was identified as fluoroacetaldehyde which is metabolised by isolated perfused rabbit hearts into fluoroacetate (FAC), a highly cardiotoxic compound. FAC was also detected in the urine of patients treated with FU. These impurities were found to be degradation products of FU that . However, the precise biochemical mechanism underlying this toxic side-effect still remains unknown even if the metabolic pathways of FU have now been largely elucidated (Heidelberger et al., 1983). The cytotoxic activity of this drug stems from the anabolic pathway that leads to fluoronucleosides (FNUCs) then fluoronucleotides (FNUCt). The degradative pathway of FU biotransformation is called the catabolic pathway and mainly leads to a-fluoro-p-alanine (FBAL), an a-fluoro-13-amino-acid which closely resembles the natural P-amino-acid, 0-alanine. P-alanine is converted into acetate which enters the Krebs cycle and undergoes a metabolic conversion to citrate. By analogy with the natural substrate, it has been suggested but never demonstrated that FBAL might be transformed into fluoroacetate (FAC) (Philips et al., 1959;Koenig & Patel, 1970;Matsubara et al., 1980). FAC is known to be a highly cardiotoxic and neurotoxic poison. Indeed, it also enters the Krebs cycle, is then transformed into fluorocitrate (FC) which inhibits citrate metabolism resulting in accumulation of intracellular citrate (Pattison & Peters, 1966) (Figure 1).Having at our disposal a powerful method for studying the metabolism of fluorinated drugs, especially fluoropyrimidines (Malet-Martino et al., 1990), we explored the possibility of a direct toxic effect of FU or one of its metabolites on the mycocardium using fluorine-19 nuclear magnetic resonance ('9F NMR) and the isolated perfused rabbbit heart (IPRH) model. We also report in this paper the results of the '9F NMR analysis of biofluids from patients treated with FU. We demonstrate that a degradation compound of FU, resulting from the storage of this drug in alkaline conditions and found in the injected vials, is responsible for the cardiotoxicity of this antineoplastic drug since it is metabolised into FAC. Materials and methods MaterialsCommercial FU Roche vials from France (50 mg FU ml-' of an aqueous solution buffered with Tris, pH = 8.5), Germany (25 mg FU ml-' of an aqueous NaOH solution, pH = 8.5), Great Britain (25 mg FU ml-I of an aqueous NaOH solution, pH = 8.5), USA (50 mg FU ml-of an aqueous NaOH solution, pH = 9.2) and a commercial US generic from SoloPak Laboratories (50 mg FU ml-' of an aqueous NaOH solution, pH = 9

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“…More than two dozen plant species are known to synthesize fluoroacetate and most of these are from Australia (Weinstein et ai., 1972;Peters, 1972). Other compounds containing C-F bonds appear in these plants, including w-fluorooleic, w-fluorocaproic, wfluoromyristic, w-fluoropalmitic, fluorocitric, fluoropyruvate, and fluoroma-Ionic acids and esters (Pattison and Peters, 1966). However, there has been produced no evidence for fluorine-containing amino acids in plants that synthesize other fluorine-containing materials (Fowden, 1972).…”

Section: Fluorine Magnetic Resonance In Biochemistry 1 Introductionmentioning

confidence: 99%

Biological Magnetic Resonance

1978

Biological Magnetic Resonance

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Monofluoro Aliphatic Compounds

Cited by 14 publications

References 161 publications

Organic Fluorine Chemistry

Organic Fluorine Chemistry

Cardiotoxicity of commercial 5-fluorouracil vials stems from the alkaline hydrolysis of this drug

Biological Magnetic Resonance

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