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

The synthesis of 8‐aza‐2′‐deoxyadenosine ( = 7‐amino‐3 H ‐1,2,3 triazolo[4,5‐ d ]pyrimidine N 3 ‐(2′‐deoxy‐β‐D‐ribofuranoside); 1 ) as well as the N 2 ‐ and N 1 ‐(2′‐deoxy‐β‐D‐ribofuranosides) 2 and 3 is described. Glycosylation of the anion of 7‐amino‐3 H ‐1,2,3‐triazolo[4,5‐ d ]pyrimidine ( 6 ) in DMF yielded three regioisomeric protected 2′‐deoxy‐β‐D‐ribofuranosides, i.e. the N 3 ‐, N 2 ‐, and N 4 ‐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‐3 H ‐1,2,3‐triazolo[4,5‐ d ]pyrimidine ( 13 ) was glycosylated in MeCN: only the N 3 ‐, N 2 , and N 1 ‐(2′‐deoxy‐β‐D‐nucleosides) 14 (29%), 15 (32%), and 16 (23%), respectively, were formed (Scheme 2). NH 3 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 13 C‐NMR , 1 H‐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.