Synthesis of GD3-lactam: a potential ligand for the development of an anti-melanoma vaccine.
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.
Hossain
Nafizal
N
Center for Chemistry and Chemical Engineering, Organic and Bioorganic Chemistry, Lund University, PO Box 124, SE-221 00 Lund, Sweden.
Zapata
Amparo
A
Wilstermann
Mikael
M
Nilsson
Ulf J
UJ
Magnusson
Göran
G
D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use; D005732:Gangliosides / Q000138:chemical synthesis* / Q000737:chemistry; D006031:Glycosylation; D007167:Immunotherapy; D007769:Lactams / Q000737:chemistry*; D008545:Melanoma / Q000276:immunology / Q000628:therapy; D009844:Oligosaccharides / Q000138:chemical synthesis / Q000737:chemistry
D019496:Cancer Vaccines; D005732:Gangliosides; D007769:Lactams; D009844:Oligosaccharides; C026226:ganglioside, GD3