The synthesis of 8-aza-3-deazaguanosine [6-amino-1-(β-D-ribofuranosyl)-υ-triazolo[4,5-c]pyridin-4-one] via a novel 1,3-dipolar cycloaddition reaction

Abstract

8-Aza-3-deazaguanosine (2) bas been prepared via a route which used a 1,3-dipolar cycloaddition reaction to provide a key intermediate. The reaction of 2′,3′,5′-tri-O-benzoyl-β-D-ribofuranosyl azide (13) with methyl 4-hydroxy-2-butynoate (11) provided a good yield of crystalline methyl 5-hydroxymethyl-1-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)-υ-triazole-4-carboxylate (14). A series of functional group transformations were then used to convert 14 into methyl 5-cyanomethyl-1-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)-υ-triazolo-4-carboxylate (19). Treatment of 19 with liquid ammonia effected not only a smooth removal of the blocking groups, but also an aminolysis of the ester function which was then followed by a ring annulation to provide 8-aza-3-deazaguanosine (2). The structures of these nucleosides were established on the basis of proton nmr spectral data and nuclear Overhauser enhancement data. The nucleosides obtained in this study were also converted through a chemical degradation sequence into nucleosides which had been obtained during an earlier work from our laboratory. The present study also provides unequivocal proof of the structures of some triazole nucleosides obtained in the earlier study.