Methodology glycopeptides

The solid-phase synthesis of glycopeptides was first realized by applying the polymeric benzyl ester principle of Merrifield. According to this methodology, Lavielle and associates (50) used 7V-(tm-butyloxycarbonyl)-<9-glycosyl serine derivative 153 for condensation with resin-linked alanine 154. 

Otvos et al. (27) adopted the Fmoc-pentafluorophenyl ester methodology and have applied O-deacetylated glycopeptide intermediates (170 and 171) for solid-phase synthesis of glycopeptides. In this way, the A-glycopep-tide (26) H-Gly-L-Lys-L-Ala-L-Tyr-L-Thr-L-Ile-L-Phe-L-... 

The convergent synthesis of glycopeptides in which the carbohydrate moiety is attached to the solid support proved an efficient alternative methodology.64 The carbohydrate structure itself was synthesized on solid support via glycal assembly and anomeric amine synthesis (Scheme 13.20). 

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 ... 

Caddick [ 19] applied this methodology in the first solid-phase radical synthesis of C-glycosides (Scheme 30). Intermolecular addition of the radical derived from iodide 135 to acceptor 132 followed by cleavage with an amino acid derivative such as phenylalanine ethyl ester gave glycopeptide 137 in good overall yield. 

In addition, Caddick [19] has extended the methodology to the successful addition of the glycosyl radical derived from glycosyl bromide 138 to acceptor 132 allowing the synthesis of glycopeptide 140 in moderate overall yield (Scheme 31). 

Table 1 summarizes the carbohydrate structural data deduced from the three detection methodologies, MALDI-TOF, ES-MS, and high pH anion exchange chromatography. The N-glycosylation site proved to be occupied with several structures. The glycopeptides were partially separated as five peptides, at retention times of 19.4, 20.3, 20.7, 20.9, and 21.3 minutes, and all of these glycopeptides contained the same amino acid sequence, N-terminal amino acids 1-17. 

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