Solution-phase glycopeptide synthesis

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

Figure 1. Solution-phase glycopeptide synthesis with solid-phase workup...

Solution-phase and solid-phase glycopeptide synthesis... 

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 ... 

In solution, phase amino acid derived methyl ester N-Fmoc-Tyr-OMe 4 was successfully condensed under Mitsunobu conditions with 2,3,4,6-tetra-Oacetyl-D-glucose 2 to afford the fully protected glucosylamine 5. The reaction provides products of analytical purity and predictable stero-chemistry, as confirmed by H/ C NMR. Synthetic conditions and protective groups for glycopeptides synthesis have been investigated. Mitsunobu conditions employed in solution phase are based on the improved redox system l,l -azodicarbonyldipiperidine (ADDP)—tributylphosphine (TBP) in... 

Fragment coupling method was first applied to glycopeptide 11 (Scheme 3). The C-terminal peptide 12 was prepared by traditional solution-phase synthesis, while the activated -terminal glycopeptide 13 was prepared by solution-phase synthesis with solid-phase workup as described. The coupling between 12 and 13 was achieved in NMP and the product was readily isolated by precipitation. Target glycopeptide 11 was obtained in 89% overall yield (28). 

Wen, S, Guo, Z, Unprotected oligosaccharides as phase tags solution-phase synthesis of glycopeptides with sohd-phase workups, Org. Lett., 3, 3773-3776, 2001. 

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]. 

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