8‐Azaguanine 2′,3′‐Dideoxyribonucleosides: Glycosylation of the 5‐amino‐7‐methoxy‐3H‐1,2,3‐triazolo[4,5‐d]pyrimidinyl anion with 2,3‐dideoxy‐D‐glycero‐pentofuranosyl chloride

Abstract

AbstractThe synthesis of the regioisomeric 8‐azaguanine N7‐, N8‐, and N9‐(β‐D‐2′,3′‐dideoxyribonucleosides) (1, 2, and 3, respectively) and of the diamino derivative 13 is described. The anion of 5‐amino‐7‐methoxy‐3H‐1,2,3‐triazolo[4,5‐d]pyrimidine (5) was glycosylated with 5‐O‐[(tert‐butyl)dimethylsilyl]‐2,3‐dideoxy‐D‐glycero‐pentofuranosyl chloride (6; anomeric mixture), yielding the regioisomeric 2′,3′‐dideoxyribofuranosides as anomeric mixtures 7a/10a, 8a/11a, and 9a/12a. They were desilylated with Bu4NF in THF affording the 5‐amino‐7‐methoxy‐nucleosides 7b–12b. Treatment with aqueous NaOH gave the 8‐azaguanine β‐D‐2′,3′‐dideoxynucleosides 1–3 and their α‐D‐anomers 14–16. The reaction of 7b with NH3/MeOH yielded the diamino compound 13. The N‐glycosylic bond of 8‐aza‐2′,3′‐dideoxyguanosine (1) is four‐times more stable against acid than that of 2′,3′‐dideoxyguanosine. Compounds 1, 2, and 13 were converted to their 5′‐triphosphates 17–19 which showed only modest inhibitory activity against HIV‐reverse transcriptase.