5-Fluoro-2 -deoxyuridine-5 -phosphate

Fluorouracil (5-FU) undergoes metabolism to form 5-fluoro-2 -deoxyuridine 5 -phosphate (5-dUMP). This metabolite forms a covalently bound ternary complex with thymidylate synthase and its coenzyme A-methylenetetrahydrofolate. The synthesis of thymine nucleotides is blocked, and a thymineless death of cells results. The answer is (E). 

When 5 -0-tritylthymidine-3 -phosphate is treated with excess tri-isopropyl benzenesulphonylchloride (TPS) and thymidine, and then deprotected, the trinucleoside monophosphate (7a) is obtained. The 5-bromo- and 5-fluoro-deoxyuridine analogues (7b) and (7c) are prepared similarly. All are resistant to snake venom and spleen phosphodiesterases, and hydrolyse too slowly under physiological conditions for the cytotoxic moiety to be effective. When protected UpU is treated with bis-(4-nitrophenyl) phosphorochloridate, and subsequently with an amine or amino-acid ester, the dinucleoside phosphor-amidates (8) are formed. Although the compounds investigated split the P—N bond under the conditions required for protecting-group removal, the method has potential for the preparation of easily fissionable neutral phospho-triesters. 

The limited therapeutic activity of the fluorinated pyrimidines 5-fluorouracil (FU) and 5-fluoro-2 -deoxyuridine (FUdR) in certain forms of adenocarcinoma, principally of the digestive tract, have led to the synthesis of a variety of analogues. Dinucleoside phosphates containing FU... 

Deoxy 3 -Deoxy-5-flnoroitridine. 5-Fluoro-3 -deoxyuridine CgHiiFNjOs 246.195 Cryst. (EtOH). Mp 169-171°. 5 -Phosphate [796-66-7]... 

Fluorouracil and six anabolites (5-fluoro- and 5-fluoro-2 -deoxyuridine and their monophosphate analogs, and uridine di- and triphosphate) were isolated from excised tumor and separated on a C,g column (A = 254 nm). Excellent peak shapes and resolution were obtained using a 100/0-> 67/33 (at 25min)-> 10/90 (at 30min)-> 0/100 (at 35min) (99/1 water [1.5mM ammonium phosphate with 1 mM tetrabutylammonium phosphate pH 3.3]/acetonitrile)/(70/30 water [25 mM ammonium phosphate with ImM tetrabutylammonium phosphate pH 3.3]/ acetonitrile) gradient [1398]. 

Fluoro-2 -deoxyuridine 5 -monophosphate has been considered to be the cytotoxic anabolite of 5-fluorouracil, but the phosphates of 5-fluorouridine are also anabolites and are incorporated into RNA. The importance of this incorporation to the action of 5-fluorouracil is under... 

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