Azolo substitution into the purine scaffold in nucleoside cyclic 3',5'-phosphorothioates

Azolation in the 8-position in the purine scaffold of cAMP (adenosine 3′,5′-cyclic monophosphate) and cAMPS (adenosine 3′,5′-cyclic monophosphorothioate) provided derivatives with an azole ring directly attached to the purine via an annular azole nitrogen. Electrophilic bromination in the 8-position was followed by nucleophilic substitution with metalated azoles to afford 8-imidazo and 8-triazolo derivatives. The substrates were appropriately protected ( S p )-3′,5′-cyclic N -benzylphosphoramidate. A subsequent carbon disulfide promoted thiation reaction afforded corresponding ( R p )-8-azolo-3′.5′-cAMPS products. The reactions were stereoselective. The products as tri- n- butylammonium salts were soluble in organic solvents and were purified by chromatography. The ammonium salts were converted to sodium salts. Graphical abstract