1,3-Dithian-2-ylmethyl Esters as Two-Step Carboxy-Protecting Groups in the Synthesis of N-Glycopeptides

Article abstract of DOI:10.1021/jo00253a003

The synthesis of totally protected N-acetylglucosaminylasparagine glycopeptides using the 1,3-dithian-2-ylmethyl (Dim) ester for selective C-terminal deprotection is described.Dim esters of amino acids can be conveniently synthesized by aluminum isopropoxide catalyzed transesterification of amino acid methyl esters with 1,3-dithian-2-ylmethanol or esterification of Boc amino acids with this alcohol followed by selective cleavage of the Boc group under acidic conditions.For the construction of N-glycopeptides Boc-asparatic acid α-Dim ester was synthesized and condensed with 2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-β-D-glucopyranosylamine.The Dim group was cleaved under very mild conditions (pH 8) after oxidation of sulfur in the dithiane ring.During this reaction the Boc group, the O-acetates, and the glycoside bond remained intact.The selectively deblocked glycosylated asparagine thus obtained was condensed with amino acid Dim esters to yield totally protected glycodipeptides in high yields.