CARB 49 |
| Intracellular postranslational phosphoprotein glycosylation, through which N-acetylglucosamine (GlcNAc) residues are beta-glycosidically linked to the hydroxy group of threonine and serine, has been observed. Furthermore, it has been shown that beta-amyloid precursor protein (APP), which is associated with Alzheimer's disease, is also postranslationally modified by O-GlcNAc residues. The specific functions of O-GlcNAc attachment to proteins have not yet been fully elucidated. Indirect evidence led to the hypothesis that O-GlcNAc linkage has a reciprocal realtionship to the regulatory effect of protein phosphorylation and dephosphorylation. Therefore, access to potential O-GlcNAc hydrolase inhibitors carrying hydrolytically stable C-linked GlcNAc residues is of great interest. To this end, C-linked D-GlcNAc-L-threonine analogue 1 has been synthesized using dilithiated D-GlcNAc precursor 2 as nucleophilic glycosyl donor (Umpolung) and L-Asp derived, amino 9-phenylfluorenyl (PhFl) protected chiral aldehyd 3 (scheme). Nucleophilic addition occurs with high Cram-selectivity, thereby yielding exclusively D-gluco-D-manno configurated Cram product 1 after complete deprotection.
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General Posters
8:00 PM-10:00 PM, Tuesday, 12 September 2006 Moscone Center -- Hall D, Poster
Division of Carbohydrate Chemistry |
