Synthesis of GD3-lactam: a potential ligand for the development of an anti-melanoma vaccine

Carbohydr Res. 2002 Apr 2;337(7):569-80. doi: 10.1016/s0008-6215(02)00036-8.

Abstract

The novel sialyl donor methyl (ethyl 4,7,8,9-tetra-O-acetyl-5-N,N-diacetylamino-3,5-dideoxy-2-thio-3-thiophenyl-D-erythro-beta-L-gluco-non-2-ulopyranosid)onate was used for glycosylation of a lactosyl acceptor to give the GM3-trisaccharide derivative in 83% yield. Introduction of an azido group at C-9" of the GM3-trisaccharide derivative, transformation into a glycosyl acceptor, and sialylation with the above mentioned novel sialyl donor gave a GD3-trisaccharide in 50% yield. Reduction of the azido group gave the corresponding amine, which underwent spontaneous lactamization to the GD3-[1"'-9"]-lactam in an overall yield of 86%. Removal of protecting groups of over five steps, followed by per-O-acetylation gave an acetylated GD3-[1"'-9"]-lactam TMSEt glycoside in 27% overall yield. The acetylated GD3-[1"'-9"]-lactam TMSEt glycoside is suitable for glycosylation of linker-arms and the resulting linker-glycosides are planned to be coupled to carrier proteins, thus providing immunogens for trial vaccinations against malignant melanoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cancer Vaccines / immunology
  • Cancer Vaccines / therapeutic use
  • Gangliosides / chemical synthesis*
  • Gangliosides / chemistry
  • Glycosylation
  • Immunotherapy
  • Lactams / chemistry*
  • Melanoma / immunology
  • Melanoma / therapy
  • Oligosaccharides / chemical synthesis
  • Oligosaccharides / chemistry

Substances

  • Cancer Vaccines
  • Gangliosides
  • Lactams
  • Oligosaccharides
  • ganglioside, GD3