Efficient Synthesis of 6-Substituted Purine Derivatives Using Pd-Catalyzed Cross-Coupling Reactions with 2’-Deoxyguanosine O6-Tosylate

Abstract

6-Substituted purine analogs function in a variety of biological activities including antiviral pathways. A number of studies have reported on the development of the efficient synthesis of these nucleoside analogs. We previously demonstrated that oligonucleotides containing 2-amino-6-vinylpurine derivatives react with the cytosine at the target site with extreme selectivity. This was the first finding that O 6 -tosylate derivative of guanosine worked as an efficient substrate for Pd(0)-catalyzed cross-coupling reaction with vinyltributylstannane to produce 2-amino-6-vinylpurine. In order to demonstrate usefulness of the tosylate precursor, in this study we investigated transition metal catalysts and ligands in achieving the cross-coupling reaction using boronic acids or Grignard reagents as a coupling partner.