Unprotected Oligosaccharides as Phase Tags for Solution-Phase Glycopeptide Synthesis with Solid-Phase Workup

Abstract

A new method was developed for glycopeptide synthesis with unprotected glycosyl amino acids as key building blocks and tags. After oligosaccharides were prepared and linked to appropriate amino acids, the carbohydrate moieties were deprotected. Glycopeptides were assembled upon the resultant glycosyl amino acids containing unprotected oligosaccharides. While all reactions for glycopeptide assembly were performed in homogeneous N-methylpyrrolidinone (NMP) solutions, the product of each reaction was expediently isolated from the reaction mixture by precipitation method via addition of a less polar solvent, such as diethyl ether. Therefore, the unprotected oligosaccharides were acting as phase tags to facilitate product isolation. The final synthetic targets were purified by HPLC. This method, which is defined as solution-phase glycopeptide synthesis with solid-phase workup, proved to be very efficient and expedient, and it has a number of advantages. It has thus been successfully employed to synthesize several complex glycopeptides, including one of CD52 with an especially acid-labile oligosaccharide chain.