Selective protection of 2-azido-lactose and in situ Ferrier rearrangement during glycosylation: synthesis of a dimeric Lewis X fragment.

In our efforts to design new anti-cancer vaccines based on the tumor associated carbohydrate antigen dimeric Le x , we have synthesized the fragment GlcNAc-β -(1→3)-Gal -β-(1→4 )-GlcNAc-β -(1→O)-Me. Although it is notoriously difficult to chemically protect the primary OH groups in β-lactoside derivatives, a 6,6'-disilylated intermediate was prepared in 82% yield. It was converted to a glycosyl acceptor free at 0-3' that was glycosylated with a 2-deoxy-2-phthalimido trichloroacetimidate glucosyl donor. This glycosylation required large amounts of TMSOTf to proceed. Such conditions led to the formation of a Ferrier rearrangement glycosylation product. Despite these hurdles, the desired trisaccharide was isolated in 53% yield and easily deprotected in four steps.