Unprotected oligosaccharides as phase tags: solution-phase synthesis of glycopeptides with solid-phase workups

[reaction--see text] N-Linked glycopeptides were synthesized from glycosyl asparagines containing unprotected oligosaccharides and other simple amino acids by an Fmoc method. The free oligosaccharide chains were used as phase tags to facilitate the product isolation by a precipitation method. Thus, while the elongation of glycopeptides was achieved in a solution of N-methylpyrrolidinone (NMP), the product of each step could be precipitated by adding ether to the reaction mixtures. The strategy also eliminated the final step of carbohydrate deprotection in glycopeptide synthesis.