Synthesis of 3,7-anhydro-D-glycero-D-ido-octitol 1,5,6-trisphosphate as anIP3 receptor ligand using a radical cyclization reaction with a vinylsilyltether as the key step. Conformational restriction strategy using steric repulsion between adjacent bulky protecting groups on a pyranose ring

3,7-Anhydro-D-glycero-D-ido-octitol 1,5,6-trisphosphate (5) was designed as a novel IP3-receptor ligand having a C-glycosidic structure and was synthe sized via a radical cyclization reaction with a temporary connecting vinyls ilyl tether as the key step. The phenyl 2-O-dimethylvinylsilyl-3,4,6-tri-O- benzyl-1-seleno-beta-D-glucopyranoside (7), in the usual C-4(1)-conformatio n, was successively treated with Bu3SnH/AIBN and under Tamao oxidation cond itions to give a mixture of five C-glycosidic products, On the other hand, similar successive treatment of the corresponding 3,4-di-O-TBS-protected su bstrates 13 and 24, which were in an unusual C-1(4)-conformaion due to the steric repulsion between the bulky silyl protecting groups, gave the desire d 1 alpha-C-glycosides 18 and 25, respectively, as the major products. Thus , the course of the radical cyclization was effectively controlled by a cha nge in the conformation of the pyranose ring into a C-1(4)-form due to ster ic repulsion between the adjacent bulky TBS-protecting groups at the 3- and 4-hydroxyl groups. From 25, the target 5 was synthesized via phosphorylati on of the hydroxyls by the phosphoramidite method. The C-glycoside trisphos phate 5 has significant binding affinity for IP3 receptor of calf cerebella .