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.
Bosse
Folkert
F
Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Marcaurelle
Lisa A
LA
Seeberger
Peter H
PH
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
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