Total synthesis of a cyclic adenosine 5'-diphosphate ribose receptor agonist.

Stable cyclic adenosine 5'-diphosphate ribose (cADPR) analogues are chemical biology tools that can probe the Ca(2+) release mechanism and structure-activity relationships of this emerging potent second messenger. However, analogues with an intact "northern" ribose have been inaccessible due to the difficulty of generating the sensitive N1-ribosyl link. We report the first total synthesis of the membrane permeant, hydrolytically stable, cADPR receptor agonist 8-Br-N1-cIDPR via regio- and stereoselective N1-ribosylation of protected 8-bromoinosine.