Preparation of glycosylated amino acids suitable for Fmoc solid-phase assembly

Many biological interactions and functions are mediated by glycans, consequently leading to the emerging importance of carbohydrate and glycoconjugate chemistry in the design of novel drug therapeutics. Despite the challenges that carbohydrate moieties bring into the synthesis of glycopeptides and glycoproteins, considerable progress has been made during recent decades. Glycopeptides carrying many simple glycans have been chemically synthesized, enzymatic approaches have been utilized to introduce more complex glycans, and most recently native chemical ligation has enabled synthesis of glycoproteins from well-designed peptide and glycopeptide building blocks. Currently, general synthetic methodology for glycopeptides relies on preformed glycosylated amino acids for the stepwise solid-phase peptide synthesis. The formation of glycosidic bonds is of fundamental importance in the assembly of glycopeptides. As such, every glycosylation has to be regarded as a unique problem, demanding considerable systematic research. In this chapter we will summarize the most common chemical methods for the stereoselective synthesis of N- and O-glycosylated amino acids. The particular emphasis will be given to the preparation of building blocks for use in solid-phase glycopeptide synthesis based on the 9-fluorenylmethoxycarbonyl (Fmoc) protective group strategy.