Synthesis of iodo-aryl-azido adenosine analogs as affinity ligands for adenylyl cyclase

Potential affinity probes for adenylyl cyclase were synthesized that take advantage of the enzyme’s sensitivity to “P”-site-mediated inhibition by 2’,5’-dideoxyadenosine analogs and its tolerance for large 3’-ribose substitutions. We report the synthesis of a series of 3’-substituted 2’,5’-dideoxyadenosine analogs. The syntheses involved the intermediate formation of symmetric anhydrides that were then coupled to 2’,5’-dideoxyadenosine by base-catalyzed esterification at the 3’-ribose position.