Design and synthesis of 4″,6″-unsaturated cyclic ADP-carbocyclic ribose as a Ca2+-mobilizing agent

4″,6″-Didehydro-cADPcR (3), an unsaturated carbocyclic ribose analog of a Ca2+-mobilizing second messenger cyclic ADP-ribose (cADPR), was designed and successfully synthesized using a key intramolecular condensation reaction forming the 18-membered pyrophosphate ring structure with a S-phenyl phosphorothioate-type substrate. Biological evaluation showed that 4″,6″-didehydro-cADPcR is a potent Ca2+-mobilizing agent in T cells.