Synthesis of Glycopeptides in Solution

Synthesis of glycopeptides in solution has been successfully applied in the preparation of glycopeptides of moderate lengths (see Sections 6.3.2 and 6.3.3). However, yields in solution synthesis are often only modest and isolation of intermediates makes the approach inconvenient. 

H Kunz, W Kosch, J Maerz, M Ciommer, W Guenther, C Unverzagt. Synthesis of glycopeptides in solution and on solid phase. Proceedings of Innovation and Perspectives in Solid Phase Synthesis. Second International Symposium, Canterbury, 1991, pp 171-178. 

The step-by-step assembly of glycopeptides in solution is still the method of choice if larger quantities of the target compounds (>1 mmol) are required. The synthesis of glycopeptides containing important but complex saccharide residues remains a major task of glycopeptide chemistry. The introduction of sialic acid residues—considered to be a limitation in the past—can now be achieved efficiently. 

The improved availability of glycosyltransferases has led to increased use of che-moenzymatic synthesis, where chemical synthesis is combined with the use of glycosyltransferases to build up saccharides on a parent glycopeptide in solution or on solid phase (Section 6.3.3.6).1200"2061... 

Scheme 27 Synthesis of Glycosylated Hydroxylysine Building Blocks and Glycopeptide in Solution Using the Glycosyl Halide as Donorl74 ...

Polystyrene-based resins have been used successfully for the solid-phase synthesis of glycopeptides and oligosaccharides. Experiments that compare the rates of a reaction on a PS-resin compared to TentaGel have revealed that the rate of reaction completely depends on the nature of the reaction itself [36], Some reactions perform better on hydro-phobic resins, while others are better on hydrophilic resins. Another issue of particular importance for the synthesis of oligosaccharides on solid phase is the influence of the solid support on the stereochemical outcome of the reaction. There are few detailed studies that address this issue however, preliminary results are contradictory, but indicate that as in solution-phase reactions, the anomeric ratio is strongly influenced by the solvent, C-2 group on the donor and temperature [37-39]. In some cases there seems to be an enhancement of anomer selectivity on the solid phase [38]. 

As for peptides, yields obtained in solution synthesis of glycopeptides are often only modest and isolation of intermediates makes the approach cumbersome when performed on a small scale. Recent efforts have therefore mainly focused on solid phase synthesis, which today constitutes the most reliable and effident method for preparation of glycopeptides (12-15). Consequently, efficient synthetic routes to glycosylated amino adds are of central importance for the preparation of glycopeptides. 

Carbohydrates and polysaccharides, on the one hand, and peptides and proteins, on the other, have been considered as separate classes of natural products for a long time. Fundamental chemical methodology for the synthesis of both saccharides and peptides was developed by Emil Fischer et al. at the beginning of the 20th century. 1,2 However, the harsh conditions employed in early solution and solid-phase peptide synthesis hindered the combination of peptide and carbohydrate chemistry, i.e. glycopeptide synthesis. Considerable efforts were made to combine the two branches of natural product chemistry, and the state of the art within glycopeptide synthesis has improved dramatically during the last decades, as described in a number of reviews. 3 23,512"514 ... 

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