Synthesis of the fully phosphorylated GPI anchor pseudohexasaccharide of Toxoplasma gondii.
Retrosynthesis of the fully phosphorylated glycosylphosphatidyl inositol (GPI) anchor pseudohexasaccharide 1a led to building blocks 2-6, of which 5 and 6 are known. The formation of pseudodisaccharide building block 2 is based on readily available building block 7, which gave, via derivative 11 and its glycosylation with known donor 12, the desired compound 2. Building block 3, with the required access to all hydroxy groups being permitted, was prepared from mannose in five steps. From a readily available precursor, building block 4 was obtained, which on reaction with 3 gave disaccharide 23. The synthesis of the decisive pseudohexasaccharide intermediate 32 was based on the reaction of 23 with 5, then with 6, and finally with 2. To obtain high stereoselectivity and good yields in the glycosylation reactions, anchimeric assistance was employed. To enable regioselective attachment of the two different phosphorus esters, the 6f-O-silyl group of 32 was first removed and the aminoethyl phosphate residue was attached. Then the MPM group was oxidatively removed, and the second phosphate residue was introduced. Unprotected 1a was then liberated in two steps: treatment with sodium methanolate removed the acetyl protecting groups, and finally, catalytic hydrogenation afforded the desired target molecule, which could be fully structurally assigned.
Pekari
K
K
Fachbereich Chemie, Universität Konstanz, Fach M725, D-78457 Konstanz, Germany.
Tailler
D
D
Weingart
R
R
Schmidt
R R
RR
D000818:Animals; D000953:Antigens, Protozoan / Q000737:chemistry; D017261:Glycosylphosphatidylinositols / Q000138:chemical synthesis*; D009844:Oligosaccharides / Q000138:chemical synthesis*; D012995:Solubility; D014122:Toxoplasma / Q000737:chemistry* / Q000276:immunology
D000953:Antigens, Protozoan; D017261:Glycosylphosphatidylinositols; D009844:Oligosaccharides