No abstract

5-Fluoro-1,3-oxazine-2,6(3H)-dione (3-oxa-FU) was synthesized by reacting 3-oxauracil with fluoroxytrifluoromethane and decomposing the adduct in the presence of a catalytic amount of Et3N. 5-Methyl-1,3-oxazine-2,6(3H)-dione (3-oxathymine) was prepared by polyphosphoric acid catalyzed ring closure of beta-(N-ethoxycarbonylamino)-2-methacrylic acid and by treatment of citraconimide with sodium hypochlorite. As determined in vitro, 3-oxa-FU was markedly inhibitory to S. faecium (ID50 = 9 X 10(-8) M) and E. coli (ID50 = 1 X 10(-7) M) but was less active against leukemia L-1210 cells (ID50 = 1 X 10(-5) M). At 1 x 10(-4) M, 3-oxathymine was inactive in these cell systems. Inhibition of the growth of S. faecium by 3-oxa-FU was reversed competitively by the natural pyrimidines. The relatively rapid hydrolysis of the compounds in the growth media is a major factor in determining their biological effectiveness.

Beim Behandeln mit Phosphorpentoxid geben die beiden β‐N‐Äthoxycarbonylamino‐acrylsäuren (Ia) und (Ib) die Dihydrooxazindione (IIa) und (IIb), die in Form der Silylverbindungen zu den Nucleosiden (IIIa) und (IIIb) kondensiert werden.

Das Oxauracil (I) liefert mit Fluoroxytrifluormethan ein Addukt, das mit Triethylamin zu (II) zersetzt wird.