Linear synthesis of the tumor-associated carbohydrate antigens Globo-H, SSEA-3, and Gb3

J Org Chem. 2002 Sep 20;67(19):6659-70. doi: 10.1021/jo025834+.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antigens, Neoplasm
  • Antigens, Tumor-Associated, Carbohydrate / chemistry*
  • Carbohydrate Sequence
  • Catalysis
  • Combinatorial Chemistry Techniques / methods*
  • Galactosides / chemical synthesis*
  • Galactosides / chemistry
  • Glycosphingolipids / chemical synthesis*
  • Glycosylation
  • Magnetic Resonance Spectroscopy
  • Molecular Structure
  • Oligosaccharides / chemical synthesis*
  • Oligosaccharides / chemistry
  • Stage-Specific Embryonic Antigens
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Antigens, Neoplasm
  • Antigens, Tumor-Associated, Carbohydrate
  • Galactosides
  • Gb3 antigen
  • Globo-H
  • Glycosphingolipids
  • Oligosaccharides
  • Stage-Specific Embryonic Antigens
  • stage-specific embryonic antigen-3