Construction Of High-efficiency Stereo-?-mannosidic Linkages And Their Applications

?-Mannosides are important structural units of natural products and natural glycans such as mannans,glycolipids and N-linked glycoproteins.Many of the compounds containg ?-mannosides unit play important roles in biological activities that include cell signaling,protein folding and immune responses.In addition,some of antibiotics widely used in clinic also have ?-mannoside motifs.Therefore,highly steroselective construction of p-mannosidic linkage is of great importance.The stereoselective synthesis of ?-mannosides has been recognized as one of the great challenges in glycochemistry since both the anomeric effect and the steric effect of the C2 axial substituent on the mannopyranosyl ring favor the formation of a-mannosides.Therefore,it is difficult to construct p-mannoside bonds.In this study,we developed a new strategy for highly steroselective construction of?-mannosides by using of a lactone donor via C4 remote acyl group participation and the assistance of C4 substituent's steric effect.The remote acyl participation and steric effect are enabled through the conversion of a regular mannopyranosyl 4C1 conformation into 2,6-lactone confromation.The lactone donor were readily prepared in 3 steps on a gram scale and the ?-mannosylation proceeded smoothly with high stereoselectivity for primary,secondary and tertiary alcohol acceptors.Furthermore,both p-mannuronic acids and ?-mannosides can be rapidly synthesized just by ring-opening of the lactone via hydrolysis or reduction after glycosylation.In addition,this strategy was applied successfully to synthesize a natural product of trisaccharide.