Exploration of Modalities in Building α-O-Linked Systems through Glycal Assembly: A Total Synthesis of the Mucin-Related F1α Antigen

The total synthesis of the F1α antigen, a member of the tumor-associated O-linked mucin glycopeptides, was achieved via two alternative routes. In the first approach, an α-O-linkage between serine/threonine and GalNAc (2-deoxy-2- N -acetylamino- d -galactose) was fashioned first. This prebuilt cassette was then linked to a lactosamine unit. Alternatively, assembly of the trisaccharide glycal preceded activation of the glycal double bond and the construction of the glycopeptide linkage. Both strategies lead to the desired glycosyl amino acid derivatives. During our investigation, we uncovered remarkable effects of even remote protecting groups on the reactivity and stereoselectivity of glycosidations.