Intracellular Ca2+-mobilizing adenine nucleotides. Synthesis and biological activity of cyclic ADP-carbocyclic-ribose and C-glycosidic analog of adenophostin A

We designed novel Ca2+-mobilizing purine nucleotides, cyclic ADP-carbocycli cribose 4, and its inosine congener 5, and C-glycosidic adenophostin A 6. I n the synthesis of cADPR analogs, the intramolecular condensation to form t he pyrophosphate linkage should be the key step. We developed an efficient method for forming such an intramolecular pyrophosphate linkage by the acti vation of the phenylthiophosphate group with I-2 or AgNO3. Using this metho d, we achieved to synthesize the target compounds 4 and 5. The synthesis of C-glycosidic analog 6 of adenophostin A was achieved using a temporary sil icon-tethered radical coupling reaction for constructing (3'alpha, 1 " alph a)-C-glycosidic structure as the key step.