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

Abstract

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.