Synthesis of Glucuronides of Fluoropyrimidine Drugs: N- and O-Glucuronides of 5-Fluorocytosine and 5-Fluorouracil

Abstract

The protected (4a-9a) and deprotected (4b-6b, 8b) glucuronides of 5-fluorocytosine and 5-fluorouracil were synthesized and characterized by mass spectrometry and ¹⁹F, ¹H and ¹³C NMR. The substitution position of the sugar moiety on the pyrimidine ring was determined from the ¹³C NMR chemical shift of the C1′ of the sugar. The α or β configuration of the glucuronide linkage was assigned on the basis of the value of the coupling constant between H1′ and H2′ of the sugar.