Synthesis of 5′-Substituted Derivatives of the Pyrrolo[2,3-d]-Pyrimidine Nucleoside Sangivamycin and Their Effect on Protein Kinase A and C Activity

Under cell-free conditions, where the antibiotic sangivamycin is not phosphorylated, it is an effective inhibitor of PKC and to a lesser extent of PKA activity. In intact cells, the antibiotic is phosphorylated, thereby, extending its range of activity to other targets including DNA and RNA. To preserve selective inhibitory activity for the protein kinases, analogs potentially resistant to phosphorylation were prepared by replacing the 5′-hydroxy group with O-nitro, O-sulfamoyl, O-methane-sulfonyl or azido groups. These compounds were more potent inhibitors of PKA and PKC activity than was the parent nucleoside.