Ganglioside GQ1b: efficient total synthesis and the expansion to synthetic derivatives to elucidate its biological roles

J Org Chem. 2009 Apr 17;74(8):3009-23. doi: 10.1021/jo8027888.

Abstract

The convergent total synthesis of ganglioside GQ1b based on the "cassette approach" between the nonreducing end GQ1b-core heptasaccharide and glucosylceramide building blocks was accomplished in high overall yield. The use of a sialylalpha(2-->8)sialylalpha(2-->3)galactose sequence as the key building block enhanced the efficiency of the glycan assembly and led to preparative-scale synthesis readily applicable for large-scale preparation. In addition, a judicious choice of p-methoxybenzyl protecting groups on glucosylceramide provided a solution to the previous synthetic problems, including a decrease in the yield of the deprotection steps, and led to elevation of the total yield. Furthermore, unnatural-type GQ1b derivatives were synthesized systematically in good yields by capitalizing on a similar approach in order to elucidate their biological roles.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carbohydrate Sequence
  • Chromatography, Gel
  • Crystallography, X-Ray
  • Galactose / analogs & derivatives*
  • Galactose / chemical synthesis
  • Galactose / chemistry
  • Gangliosides / chemical synthesis*
  • Glucosylceramides / chemistry
  • Glycosphingolipids / chemistry
  • Magnetic Resonance Spectroscopy
  • Molecular Sequence Data
  • Molecular Structure
  • Oligosaccharides / chemical synthesis*
  • Oligosaccharides / chemistry
  • Stereoisomerism

Substances

  • Gangliosides
  • Glucosylceramides
  • Glycosphingolipids
  • Oligosaccharides
  • sialylalpha(2-3)galactose
  • GQ1b ganglioside
  • Galactose