Synthesis of the C-glycosidic analogue of adenophostin A and its uracil congener as potential IP(3) receptor ligands. Stereoselective construction of the C-glycosidic structure by a temporary silicon-tethered radical coupling reaction.
Synthesis of the C-glycosidic analogue 9 of adenophostin A, a very potent IP(3) receptor agonist, and its uracil congener 10 was achieved via a temporary silicon-tethered radical coupling reaction as the key step. Phenyl 3,4, 6-tri-O-(p-methoxybenzyl)-1-seleno-beta-D-glucopyranoside (27) and 3-deoxy-3-methylene-1, 2-O-isopropylidene-alpha-D-erythro-pentofuranose (30) were connected by a dimethylsilyl tether to give the radical coupling reaction substrate 24, which was successively treated with Bu(3)SnH/AIBN in benzene and TBAF in THF to give the coupling product 25 with the desired (3alpha,1'alpha)-configuration as the major product. From 25, the targets 9 and 10 were synthesized via introduction of adenine or uracil base by Vorbrüggen's method and phosphorylation of the hydroxyls by the phosphoramidite method.
Abe
H
H
Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
Shuto
S
S
Matsuda
A
A
D000241:Adenosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D006027:Glycosides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D053496:Inositol 1,4,5-Trisphosphate Receptors; D008024:Ligands; D008958:Models, Molecular; D008968:Molecular Conformation; D018160:Receptors, Cytoplasmic and Nuclear / Q000187:drug effects / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014498:Uracil / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology
D015220:Calcium Channels; D006027:Glycosides; D053496:Inositol 1,4,5-Trisphosphate Receptors; D008024:Ligands; D018160:Receptors, Cytoplasmic and Nuclear; C085029:adenophostin A; D014498:Uracil; D015544:Inositol 1,4,5-Trisphosphate; D000241:Adenosine