Apr, 2005
Synthesis of 4,8-anhydro-D-glycero-D-ido-nonanitol 1,6,7-trisphosphate as a novel IP3 receptor ligand using a stereoselective radical cyclization reaction based on a conformational restriction strategy
TETRAHEDRON
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- Volume
- 61
- Number
- 15
- First page
- 3697
- Last page
- 3707
- Language
- English
- Publishing type
- Research paper (scientific journal)
- DOI
- 10.1016/j.tet.2005.02.025
- Publisher
- PERGAMON-ELSEVIER SCIENCE LTD
4,8-Anhydro-D-glycero-D-ido-nonanitol 1,6,7-trisphosphate (9), designed as a novel IP3 receptor ligand having an alpha-C-glycosidic\ structure, was synthesized via a radical cyclization reaction with a temporary connecting allylsilyl group as the key-step. Phenyl 2-O-allyldimethylsilyt-3,4-bis-O-TBS-1-seleno- beta-D-glucopyranoside (10a), conformationally restricted in the unusual C-1(4)-conformation, was treated with Bu3SnH/AIBN to form the desired alpha-cyclization product 16a almost quantitatively. On the other hand, when a conformationally unrestricted O-benzyl-protected 2-O-allyldimethylsilyl -l-selenoglucoside 15 was used as the substrate, the radical reaction was not stereoselective and gave a mixture of the alpha-and beta-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 Ca2+ mobilization, although its activity was weaker than that of the natural ligand IP3. Thus, the alpha-C-glucosidic structure was shown to be a useful mimic of the myo-inositol backbone of IP3. (c) 2005 Elsevier Ltd. All rights reserved.
- Link information
- ID information
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- DOI : 10.1016/j.tet.2005.02.025
- ISSN : 0040-4020
- Web of Science ID : WOS:000228147400008