Pyrimidines, fluoro-, formation

Treatment of the enol tosylate obtained with amines led to the formation of / -amino-a-fluoro acrylaldehydes (Eq. 90) when bifunctional nitrogen nucleophiles were used, pyrazoles and pyrimidines were obtained [267]. More recently the reaction has been used to prepare the alkyl- or arylthio congeners [268]. 

Radiolabelled derivatives of the herbicide florasulam (N-(2,6-difluo-rophenyl)-5-methoxy-8-fluoro(l,2,4)-triazolo-[l,5-c]-pyrimidine-2-sulphon-amide) (VII) were exposed to natural sunlight in a sterile pH 5 buffer water and in a natural lake water collected from 20 to 30 cm below the surface [70]. The photo degradation was much faster in the natural water system, with a half-life of 3.3 days against 73 days in the buffered aqueous medium. Moreover, the photoproducts produced in the distilled and natural waters were found to be different. Direct photolysis led to the cleavage of the N - S bond with formation of the sulphonic acid derivative (Vila) after 10% of conversion (see Scheme 7). 

Capecitabine is a pyrimidine analog. It is an oral systemic prodrug that is enzymatically converted to 5-fluorouracil (5-FU). Healthy and tumor cells metabolize 5-FU to 5-fluoro-2-deoxyuridine monophosphate (FdUMP) and 5-flu-orouridine triphosphate (FUTP). These metabolites cause cell injury by two different mechanisms. First, they inhibit the formation of thymidine triphosphate, which is essential for the synthesis of DNA. Second, nuclear transcriptional enzymes can mistakenly incorporate FUTP during the synthesis of RNA. This metabolic error can interfere with RNA processing and protein synthesis. Capecitabine is indicated in the treatment of resistant metastatic breast cancer alone or in combination with docetaxel, and colorectal cancer. 

Mukherjee KL, Heidelberger C (1962) Studies of fluorinated pyrimidines. XV. Inhibition of the incorporation of formate-C14 into DNA thymine of ehrlich ascites carcinoma cells by 5-fluoro-2 -deoxyuridine-5 -monophosphate and related compounds. Cancer Res 22 815-822... 

In another work, fluoromethyl group in pyrimidines 1225 acted as CH-acid in an intramolecular condensation with carbonyl compound, leading to the formation of 8-fluoro-pyrrolo[l,2-a]pyrimid-4-one derivatives 1226 (Schane 268) [358,756],... 

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