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 Lex, we have synthesized the fragment GlcNAc-beta-(1-->3)-Gal-beta-(1-->4)-GlcNAc-beta-(1-->O)-Me. Although it is notoriously difficult to chemically protect the primary OH groups in beta-lactoside derivatives, a 6,6'-disilylated intermediate was prepared in 82% yield. It was converted to a glycosyl acceptor free at O-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.
Wang
An
A
Department of Chemistry, University of Guelph, Guelph, Ontario N1G 2W1, Canada.
Auzanneau
France-Isabelle
FI
D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D002625:Chemistry, Organic / Q000379:methods*; D019281:Dimerization; D005690:Galactose / Q000737:chemistry; D006031:Glycosylation; D007785:Lactose / Q000737:chemistry; D016256:Lewis X Antigen / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data
D016256:Lewis X Antigen; D007785:Lactose; D005690:Galactose