Intracellular Ca(2+)-mobilizing adenine nucleotides. Synthesis and biological activity of cyclic ADP-carbocyclic-ribose and C-glycosidic analog of adenophostin A.
We designed novel Ca(2+)-mobilizing purine nucleotides, cyclic ADP-carbocyclicribose 4, and its inosine congener 5, and C-glycosidic adenophostin A 6. In the synthesis of cADPR analogs, the intramolecular condensation to form the pyrophosphate linkage should be the key step. We developed an efficient method for forming such an intramolecular pyrophosphate linkage by the activation of the phenylthiophosphate group with I2 or AgNO3. Using this method, 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 silicon-tethered radical coupling reaction for constructing (3'alpha, 1" alpha)-C-glycosidic structure as the key step.
Shuto
S
S
Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan. shu@pharm.hokudai.ac.jp
Fukuoka
M
M
Abe
H
H
Matsuda
A
A
D000227:Adenine Nucleotides / Q000138:chemical synthesis* / Q000494:pharmacology*; D000241:Adenosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002120:Calcium Channel Agonists / Q000138:chemical synthesis* / Q000494:pharmacology*; D015220:Calcium Channels / Q000378:metabolism; D006027:Glycosides / Q000138:chemical synthesis / Q000494:pharmacology; D053496:Inositol 1,4,5-Trisphosphate Receptors; D008024:Ligands; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism
D000227:Adenine Nucleotides; D002120:Calcium Channel Agonists; D015220:Calcium Channels; D006027:Glycosides; D053496:Inositol 1,4,5-Trisphosphate Receptors; D008024:Ligands; D018160:Receptors, Cytoplasmic and Nuclear; C085029:adenophostin A; D000241:Adenosine; D002118:Calcium