Improved Synthesis of Phosphoramidite-Protected -Methyladenosine via BOP-Mediated SAr Reaction.

-methyladenosine(mA) is the most abundant modification in mRNA. Studies on proteins that introduce and bind mA require the efficient synthesis of oligonucleotides containing mA. We report an improved five-step synthesis of the mA phosphoramidite starting from inosine, utilising a 1--benzotriazol-1-yloxytris(dimethylamino)phosphoniumhexafluorophosphate (BOP)mediated SAr reaction in the key step. The route manifests a substantial increase in overall yield compared to reported routes, and is useful for the synthesis of phosphoramidites of other adenosine derivatives, such as ethanoadenosine, an RNA analogue of the DNA adduct formed by the important anticancer drug Carmustine.