(2-O-hexadecyl)PI], were tested as substrates or inhibitors of glycosylphosphatidylinositol (GPI) bio-synthetic pathways using cell-free systems of the proto-zoan parasite Trypanosoma brucei (the causative agent of human African sleeping sickness) and human HeLa cells. Neither these compounds nor their N-acetyl derivatives are substrates or inhibitors of GPI bio-synthetic enzymes in the HeLa cell-free system but are potent inhibitors of GPI biosynthesis in the T.brucei cell-free system. GlcN-(2-O-hexadecyl)PI was shown to inhibit the first α-mannosyltransferase of the trypano-somal GPI pathway. The N-acetylated derivative GlcNAc-(2-O-octyl)PI is a substrate for the trypano-somal GlcNAc-PI deN -acetylase and this compound, like GlcN-(2-O-octyl)PI, is processed predominantly to Man 2 GlcN-(2-O-octyl)PI by the T.brucei cell-free system. Both GlcN-(2-O-octyl)PI and GlcNAc-(2-O-octyl)PI also inhibit inositol acylation of Man 1-3 GlcN-PI and, consequently, the addition of the ethanolamine phosphate bridge in the T.brucei cell-free system. The data establish these substrate analogues as the first generation of in vitro parasite GPI pathway-specific inhibitors.

This report describes a simple synthesis of 2-azido-3,4,6-tri-O-benzyl-2-deoxy-d-glucopyranose. Glycosylation using this as well as 2-azido-3,4,6-tri-O-benzyl-2-deoxy-d-galactopyranose and -mannopyranose was achieved with the aid of a reagent system consisting of p-nitrobenzenesulfonyl chloride, silver trifluoromethanesulfonate, and triethylamine, and its modifications. O-(2-Acetamido-2-deoxy-β-d-glucopyranosyl)-(1→4)-O-α-d-mannopyranosyl-(1→4)-α-d-mannopyranose, the repeating unit of the main chain of the O-specific cell wall polysaccharide of E. coli 058 was synthesized.

The one-stage β-glucosylation of benzyl 3-O-acetyl-2,4-di-O-benzyl-α-D-glucopyranoside (1) with 2,3,4,6-tetra-O-benzyl-α-D-glucopyranose (2) using a mixture of p-nitrobenzenesulfonyl chloride, silver trifluoromethanesulfonate, and triethylamine, followed by deacetylation, gave benzyl O-(2,3,4,6-tetra-O-benzyl-β-D-glucopyranosyl)-(1 → 6)-2,4-di-O-benzyl-α-D-glucopyranoside (3). The disaccharide derivative 3 was then subjected to the β-glucosylation, followed by catalytic hydrogénation, to afford O-β-D-glucopyranosyl-(1 → 3)-O-[β-D-glucopyranosyl-(1 → 6)]-D-glucopyranose (4). The key intermediate 1 was prepared from D-glucose by way of a Fischer reaction, triphenylmethylation, a controlled benzylation, and detriphenylmethylation.

d-Glucose, d-galactose, d-mannose, d-xylose, l-arabinose, l-fucose, l-rhamnose, maltose, cellobiose, lactose, d-glucosamine, d-galactosamine, and d-mannosamine were converted into the corresponding methyl per-O-acetyl 1-thioglycopyranosides by way of a three-step (acetobromination, methylthioation, and acetylation) through-process in a single vessel.

Ausgehend vom Glucosid (Ia) ist über die Stufen (Ib), (Ic) und (IIa) das Derivat (IIb) erhältlich, dessen Kondensation mit der Tetra‐O‐benzylglucose (III) unter den angegebenen Bedingungen ein Gemisch der anomeren Disaccharide (IVa) + (IVb) liefert; analoge weitere Umsetzung von (IVa) mit (III) gibt die Trisaccharid‐Derivate (IVc) + (IVd).