Solid-phase synthesis of glycopeptide carrying a tetra-N-acetyllactosamine-containing core 2 decasaccharide

A novel synthesis of tetralactosaminyl O-glycoamino acid is described The stereoselective assemblage of a lactosaminyl unit was performed by 2-trichloroacetamido group-assisted beta-glycosylation. Initial investigation into the synthesis of decasaccharyl threonine 2 showed limited Success because of the low yield in the step concerning the removal of 4-O-chloroacetyl groups In contrast, 4-O-benzylated decasaccharyl threonine 50 was efficiently synthesized from key LacNAc derivative 35 carrying a 3-O-allyl protecting group at the Gal residue by reiterative glycosylation using the (N-phenyl)trifluoroacetimidate method Decasaccharide 50 was used as a building block in the solid-phase synthesis of a MUC1-related glycopeptide Synthetic glycopeptide was obtained through two acidic processes cleavage from resin with reagent K at a lowered temperature and debenzylation with a diluted cocktail of low-acidity TfOH Desired glycopeptide 54 was isolated as the major product, while a series of the saccharide-shortened minor products were generated due to the acid-labile property of the beta-GlcNAc glycosidic linkages (C) 2009 Elsevier Ltd All rights reserved