The synthesis of C8-Aryl purines, nucleosides, and phosphoramidites

C8-Aryl purines, their nucleosides, and phosphoramidites have been synthetic targets for more than 60 years. Interest in these compounds stems from their utility as fluorescent markers, biomarkers, biomolecular probes, and supramolecular building blocks, as well as their uses in therapy and for conformational studies. Until recently, the selective arylation of the C8 position of purines has been a challenging task. Several approaches have been explored, including building them up from a pyrimidine or selective C8 modification of an unsubstituted purine. Neither of these approaches has proven to have broad scope. The discovery that C8-aryl purine nucleosides can be made via the Suzuki cross-coupling reaction has allowed a diverse array of analogs to be prepared and, in turn, the corresponding phosphoramidites. The latter is particularly significant as C8-aryl purine adducts are a major mutation observed from aromatic carcinogens, and ready access to C8-aryl phosporamidites will facilitate the synthesis and study of C8-aryl purine biomarkers and modified oligonucleotides.