Linear synthesis of the tumor-associated carbohydrate antigens globo-h, SSEA-3, and Gb3

The tumor-associated carbohydrate antigens Globo-H, SSEA-3, and Gb3 were synthesized in a linear fashion using glycosyl phosphate monosaccharide building blocks. All of the building blocks were prepared from readily available common precursors. The difficult alpha-(1-->4-cis)-galactosidic linkage was installed using a galactosyl phosphate donor with high selectivity. Introduction of the beta-galactosamine unit required the screening a variety of amine protecting groups to ensure good donor reactivity and protecting group compatibility. An N-trichloroacetyl-protected galactosamine donor performed best for the installation of the beta-glycosidic linkage. Conversion of the trichloroacetyl group to the N-acetyl group was achieved under mild conditions, fully compatible with the presence of multiple glycosidic bonds. This synthetic strategy is expected to be amenable to the synthesis of the globo-series of tumor antigens on solid-support.