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4,8-Anhydro-d-glycero-d-ido-nonanitol 1,6,7-trisphosphate (9), designed as a novel IP 3 receptor ligand having an α-C-glycosidic structure, was synthesized via a radical cyclization reaction with a temporary connecting allylsilyl group as the key-step. Phenyl 2-O-allyldimethylsilyl-3,4-bis-O-TBS-1- seleno-β-d-glucopyranoside (10a), conformationally restricted in the unusual 1 C 4 -conformation, was treated with Bu 3 SnH/AIBN to form the desired α-cyclization product 16a almost quantitatively. On the other hand, when a conformationally unrestricted O-benzyl-protected 2-O-allyldimethylsilyl -1-selenoglucoside 15 was used as the substrate, the radical reaction was not stereoselective and gave a mixture of the α-and β-products. From 16a, the target C-glucoside trisphosphate 9 was synthesized via phosphorylation of the hydroxyls by the phosphoramidite method. During the synthetic study, an efficient procedure for the oxidative C-Si bond cleavage, via a nucleophilic substitution at the silicon with p-MeOPhLi followed by Fleming oxidation, was developed. The C-glycoside 9 was found to be a full agonist for Ca 2+ mobilization, although its activity was weaker than that of the natural ligand IP 3 . Thus, the α-C-glucosidic structure was shown to be a useful mimic of the myo-inositol backbone of IP 3 . © 2005 Elsevier Ltd. All rights reserved.

Original publication

DOI

10.1016/j.tet.2005.02.025

Type

Journal article

Journal

Tetrahedron

Publication Date

11/04/2005

Volume

61

Pages

3697 - 3707