The synthesis of β-mannopyranosides by intramolecular aglycon delivery: scope and limitations of the existing methodology

Abstract

The synthesis of β-mannopyranosides by intramolecular aglycon delivery is shown to proceed with complete stereoselectivity in six separate cases. This strategy has been successfully applied to the synthesis of several disaccharides, including octyl 3,6-di-O-benzyl-4-O-(3,4,6-tri-O-benzyl-β-D-mannopyranosyl)-2-deoxy-2-phthalimido-β-D-glucopyranoside, a precursor of the naturally occurring β-D-Man-(1→4)-β-D-GlcNAc linkage, present in all N-linked glycoproteins. Exclusive formation of the β-mannosidic linkage has been confirmed in all six cases, since independently synthesized α-linked mannopyranoside standards were shown to be absent from the reaction products. The intramolecular stereocontrolled reaction proceeds even in the presence of competing methanol. The extension of this strategy to the synthesis of the core pentasaccharide of N-linked glycoproteins has revealed limitations to the methodology, especially when a block synthesis approach is investigated.