Synthesis of a core trisaccharide building block for the assembly of N-glycan neoconjugates

A short and high yielding synthesis of a core trisaccharide 1 as the key building block in the assembly of a library of N-glycan neoconjugates is presented. The β-d-Manp-(1→4)-d-GlcpNAc linkage was introduced by inversion of the C-2 position of a β-glucoside. The glucosyl donor was efficiently synthesised following a recently published one-pot strategy. 2-Naphthylmethyl and benzylidene-acetal protection in the terminal mannose permitted selective liberation of main branching sites for subsequent glycosylation. A C5 azido linker attached to the anomeric position, which is stable throughout the synthesis, will allow for the posterior immobilisation of deprotected glycans on a microarray surface.

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p-Toluenyl 4,6-O-benzylidene-2-O-levulinoyl-3-O-(2-naphthylmethyl)-l-thio-β-d-glucopyranosideC36H36O7SiEe = 100%[α]D20=+7.3 (c 0.76, CHCl3)Source of chirality: d-glucose

tert-Butyldimethylsilyl 4,6-O-benzylidene-2-O-levulinoyl-3-O-(2-naphthylmethyl)-β-d-glucopyranosyl-(l→4)-3,6-di-O-benzyl-2-deoxy-2-phthalamido-β-d-glucopyranosideC63H69NO14SiEe = 100%[α]D20=+5.7 (c 0.5, CHCl3)Source of chirality: d-glucose, d-glucosamine

tert-Butyldimethylsilyl 4,6-O-benzylidene-3-O-(2-naphthylmethyl)-β-d-glucopyranosyl-(l→4)-3,6-di-O-benzyl-2-deoxy-2-phthalamido-β-d-glucopyranosideC58H63NO12SiEe = 100%[α]D20=+22.1 (c 0.95, CHCl3)Source of chirality: d-glucose, d-glucosamine

tert-Butyldimethylsilyl 2-O-acetyl-4,6-O-benzylidene-3-O-(2-naphthylmethyl)-β-d-mannopyranosyl-(l→4)-3,6-di-O-benzyl-2-deoxy-2-phthalamido-β-d-glucopyranosideC60H65NO13SiEe = 100%[α]D20=+3.0 (c 0.20, CHCl3)Source of chirality: d-mannose, d-glucosamine

tert-Butyldimethylsilyl 4-O-acetyl-3,6-di-O-benzyl-2-deoxy-2-phthalamido-β-d-glucopyranosideC36H43NO8SiEe = 100%[α]D20=+47.2 (c 1.06, CHCl3)Source of chirality: d-glucosamine

4-O-Acetyl-3,6-di-O-benzyl-2-deoxy-2-phthalamido-β-d-glucopyranoside N-phenyl trifluoroacetimidateC38H33F3N2O8Ee = 100%[α]D20=+246.0 (c 2.90, CHCl3)Source of chirality: d-glucosamine

5-Azidopentyl 4-O-acetyl-3,6-di-O-benzyl-2-deoxy-2-phthalamido-β-d-glucopyranosideC35H38N4O8Ee = 100%[α]D20=+122.6 (c 2.70, CHCl3)Source of chirality: d-glucosamine

5-Azidopentyl 3,6-di-O-benzyl-2-deoxy-2-phthalimido-β-d-glucopyranosideC33H36N4O7Ee = 100%[α]D20=+36.0 (c 0.9, CHCl3)Source of chirality: d-glucosamine

5-Azidopentyl 2-O-acetyl-4,6-O-benzylidene-3-O-(2-naphthylmethyl)-β-d-mannopyranosyl-(l→4)-3,6-di-O-benzyl-2-deoxy-2-phthalamido-β-d-glucopyranosyl-(l→4)-3,6-di-O-benzyl-2-deoxy-2-phthalamido-β-d-glucopyranosideC83H77N5O19Ee = 100%[α]D20=+3.9 (c 0.15, CHCl3)Source of chirality: d-mannose, d-glucosamine