title: Linear synthesis of the tumor-associated carbohydrate antigens Globo-H, SSEA-3, and Gb3.
abstract: 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.
authors.affiliation: Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
authors.forename: Folkert
authors.initials: F
authors.lastname: Bosse
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Marcaurelle
authors.forename: Peter H
authors.initials: PH
authors.lastname: Seeberger
mesh_terms: D000951:Antigens, Neoplasm; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000737:chemistry*; D002240:Carbohydrate Sequence; D002384:Catalysis; D020650:Combinatorial Chemistry Techniques / Q000379:methods*; D005697:Galactosides / Q000138:chemical synthesis* / Q000737:chemistry; D006028:Glycosphingolipids / Q000138:chemical synthesis*; D006031:Glycosylation; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D009844:Oligosaccharides / Q000138:chemical synthesis* / Q000737:chemistry; D055746:Stage-Specific Embryonic Antigens; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000951:Antigens, Neoplasm; D015295:Antigens, Tumor-Associated, Carbohydrate; D005697:Galactosides; C472766:Gb3 antigen; C472765:Globo-H; D006028:Glycosphingolipids; D009844:Oligosaccharides; D055746:Stage-Specific Embryonic Antigens; C052924:stage-specific embryonic antigen-3