A new, but old, nucleoside analog: the first synthesis of 1‐deaza‐2′‐deoxyguanosine and its properties as a nucleoside and as oligodeoxynucleotides

摘要

The first synthesis of 5‐amino‐3‐(2′‐deoxy‐β‐d‐ribofuranosyl)imidazo[4,5‐b]pyridin‐7‐one (1‐deaza‐2′‐deoxyguanosine) is described. The compound was converted from the known AICA‐deoxyriboside. The tautomeric structure of the base moiety was determined by theoretical calculation to be a hydroxyl form. Although the analog was found to be labile to acidic conditions, 1‐deaza‐2′‐deoxyguanosine was successfully converted into a phosphoramidite derivative, which was incorporated into oligodeoxynucleotides by the standard phosphoramidite method. Thermal stabilities of oligodeoxynucleotides containing 1‐deaza‐2′‐deoxyguanosine were investigated by thermal denaturing experiments. Also, a triphosphate analog of 1‐deaza‐2′‐deoxyguanosine was synthesized for polymerase extension reactions. Single nucleotide insertion reactions using a template containing 1‐deaza‐2′‐deoxyguanosine, as well as 1‐deaza‐2′‐deoxyguanosine triphosphate, were performed using the Klenow fragment (exonuclease minus) polymerase and other polymerases. No hydrogen bonded base pairs, even a 1‐deaza‐2′‐deoxyguanosine:cytidine base pair, were indicated by thermal denaturing studies. However, though less selective and less effective than the natural guanosine counterpart, the polymerase extension reactions suggested the formation of a base pair of 1‐deaza‐2′‐deoxyguanosine with cytidine during the insertion reactions.