A new synthesis of 3-(β-D-ribofuranosyl)uracil (isouridine)via the intermediacy of an O6,5′-cyclotetrahydropyrimidinone nucleoside

Abstract

A specific and efficient synthesis for 3-(β-D-ribofuranosyl)uracil, isouridine (1), has been devised. Starting with the easily accessible 1-(β-D-ribofuranosyl)-1,2-dihydropyrimidin-2-one (3b) the C-6 carbonyl function of isouridine was built via formation of the corresponding O⁶, 5′-cyclonucleoside (5) followed by a two-step oxidation with o-chloranil and base-catalyzed hydrolysis of the intermediate 6-chloro-O⁶,5′-cyclonucleoside (12a). The resulting isopropylideneisouridine (11) was easily deblocked to give the desired target (1). A 25% overall yield of (1) from pyrimidin-2-one and 1-O-acetyl-2,3,5-tri-O-benzoyl-β-D-ribofuranose was obtained.