Synthesis of 8‐Aza‐2′‐deoxyadenosine and related 7‐Amino‐3H‐1,2,3‐triazolo[4,5‐d]pyrimidine 2′‐Deoxyribofuranosides: Stereoselective glycosylation via the nucleobase anion

Abstract

AbstractThe synthesis of 8‐aza‐2′‐deoxyadenosine ( = 7‐amino‐3H‐1,2,3 triazolo[4,5‐d]pyrimidine N3‐(2′‐deoxy‐β‐D‐ribofuranoside); 1) as well as the N2‐ and N1‐(2′‐deoxy‐β‐D‐ribofuranosides) 2 and 3 is described. Glycosylation of the anion of 7‐amino‐3H‐1,2,3‐triazolo[4,5‐d]pyrimidine (6) in DMF yielded three regioisomeric protected 2′‐deoxy‐β‐D‐ribofuranosides, i.e. the N3‐, N2‐, and N4‐glycosylated isomers 7 (14%), 9 (11%), and 11 (3%), respectively, together with nearly equal amounts of their α‐D‐anomers 8 (13%), 10 (12%), and 12 (4%; Scheme 1). The reaction became Stereoselective for the β‐D‐nucleosides if the anion of 7‐methoxy‐3H‐1,2,3‐triazolo[4,5‐d]pyrimidine (13) was glycosylated in MeCN: only the N3‐, N2, and N1‐(2′‐deoxy‐β‐D‐nucleosides) 14 (29%), 15 (32%), and 16 (23%), respectively, were formed (Scheme 2). NH3 Treatment of the methoxynucleosides 14–16 afforded the aminonucleosides 1–3. The anomeric configuration as well as the position of glycosylation were determined by combination of 13C‐NMR, 1H‐NMR, and 1D‐NOE difference spectroscopy. Compound 1 proved to be a substrate for adenosine deaminase, whereas the regioisomers 2 and 3 were not deaminated.