Application of serine- and threonine-derived cyclic sulfamidates for the preparation of S-linked glycosyl amino acids in solution- and solid-phase peptide synthesis.

Cyclic sulfamidates were synthesized in 60% yield from L-serine and allo-L-threonine, respectively. These sulfamidates reacted with a variety of unprotected 1-thio sugars in aqueous bicarbonate buffer (pH 8) to afford the corresponding S-linked serine- and threonine-glycosyl amino acids with good diastereoselectivity (> or =97%) after hydrolysis of the N-sulfates. The serine-derived sulfamidate was incorporated into a simple dipeptide to generate a reactive dipeptide substrate that underwent chemoselective ligation with a 1-thio sugar to afford an S-linked glycopeptide. This sulfamidate was also incorporated into a peptide on a solid support in conjunction with solid-phase peptide synthesis. Chemoselective ligation of a 1-thio sugar with the cyclic sulfamidate was achieved on the solid support, followed by removal of the N-sulfate. Finally, the peptide chain of the resulting support-bound S-linked glycopeptide was extended using standard peptide synthesis procedures.