Efficient Synthesis of Complex Glycopeptides Based on Unprotected Oligosaccharides.

Abstract

N-Glycopeptides containing 1 to 4 trisaccharide chains, with the carbohydrates vicinal to each other in the multivalent glycopeptides, were efficiently synthesized by using the glycosylated Fmoc-asparagine as a key building block. While the couplings of amino acids with glycopeptides could be achieved in the homogeneous solutions in N-methylpyrrolidinone (NMP) to give excellent yields, all products were conveniently isolated from the reaction mixtures through a precipitation method by using the free carbohydrate chains as phase tags. Commercially available pentafluorophenyl (Pfp) esters of amino acids were employed for the glycopeptide elongation. Longer glycopeptides were constructed by means of a highly convergent synthetic design that is based on the coupling of glycopeptide/peptide fragments. Hydrogen bond interactions between free oligosaccharides were proposed to explain the exceptionally high efficiency of the couplings between two glycosylated building blocks.