8‐Azaadenosine and Its 2′‐Deoxyribonucleoside: Synthesis and oligonucleotide base‐pair stability

The synthesis of 8‐azaadenosine ( 1a ; z 8 A) has been performed by SnCl 4 ‐catalyzed glycosylation of 8‐azaadenine ( 4 ) with 1,2,3,5‐tetra‐ O ‐acetyl‐β‐ D ‐ribofuranose ( 5 ), followed by the separation of the regioisomers 6 and 7 and subsequent deacetylation. The ribonucleoside 1a as well as its 2′‐deoxy derivative 1b (z 8 A d ) were converted into oligonucleotide building blocks–the phosphonate 2 as well as the phosphoramidites 3 and 19 . They were used to prepare the oligoribonucleotide (z 8 A‐U) 6 and oligodeoxyribonucleotides. The T m values and the thermodynamic data of duplex formation of the modified duplexes showed no significant changes compared to those containing A d or A residues. This indicates that the stereoelectronic effect of the 8‐azaadenine base which was found for the monomeric nucleoside has only a minor influence on the duplex stability.