Toward the Chemical Syntheses of Fucosylated Peptides: A Combination of Protecting Groups for the Hydroxy Groups of Fucose

Abstract

Abstract A combination of protecting groups for the hydroxy groups of fucose is presented. Notably, this combination enables the synthesis of glycopeptides containing acid-sensitive fucose. The relationship between the design of the protecting groups for the alcohols of fucose and the acid stability of the fucosidic linkage is elucidated. The hydrolysis of pseudo-glycopeptides incorporating various fucose-alcohol-protecting groups is investigated in a trifluoroacetic acid cocktail. The nature of the protecting group significantly affected the acid stability of the fucosidic bond, with a combination of 4-methylbenzyl and levulinoyl groups offering optimal protection of the fucosidic bond. These protecting groups were employed to realize the practical synthesis of glycopeptides containing fucose. To demonstrate the usefulness of this protecting group combination, a model octapeptide was synthesized by 9-fluorenylmethoxycarbonyl solid-phase peptide synthesis. The decomposition of the fucosidic linkage during the final deprotection of solid-phase peptide synthesis was prevented, yielding the desired fucosylated peptide. Finally, the remaining levulinoyl group was removed by hydrazine under neutral conditions to give the fully deprotected glycopeptide.