A synthesis of pseudouridine

Abstract

2,3,5-Tri-O-benzylribose and 2,4-di-t-butoxy-5-lithiopyrimidine (from the 5-bromo-compound and butyllithium) in THF at –78 °C give 5-(2,3,5-tri-O-benzyl-D-altro-pentahydroxypentyl)-2,4-di-t-butoxypyrimidine and its D-allo-epimer (ratio 5:2), which cyclise stereospecifically in ethanolic hydrochloric acid to 5-(2,3,5-tri-O-benzyl-β-D-ribofuranosyl)uracil and its α-anomer. Debenzylation by boron trichloride gives 5-β-D-ribofuranosyluracil, pseudouridine, and its α-anomer. 2,3,5-Tri-O-methylribose reacts analogously. 2,3-O-Isopropylideneribose and its 5-O-trityl derivative give no polyol, but instead 2,4-di-t-butoxy-5-(2-hydroxyisopropyl)pyrimidine.