SYNTHETIC STUDIES ON CELL-SURFACE GLYCANS .85. STEREOSELECTIVE TOTAL SYNTHESIS OF THE GLYCOSYL PHOSPHATIDYLINOSITOL (GPI) ANCHOR OF TRYPANOSOMA-BRUCEI

The total synthesis of O-{O-[6-O-(2-aminoethylphosphono)-alpha-D-mannopyranosyl]-(1 --> 2)-O-alpha-D mannopyranosyl-(1 --> 6)-O-[O-alpha-D-galactopyranosyl-(1 --> 6)-alpha-D-galactopyranosyl-(1 --> 3)]-O-alpha-D mannopyranosyl-(1 --> 4)-2-amino-2-deoxy-alpha-D-glucopyranosyl)-(1 --> 6)-{1-O-(1,2-dimyristoyl-sn-glycero-3-phosphono)-1D-myo-inositol}, the GPI anchor of Trypanosoma brucei was achieved for the first time. The core structure of the GPI molecule, the glycoheptaosyl part, was constructed in a highly stereocontrolled manner from O-[O-(2,4-di-O-benzyl-alpha-D-mannopyranosyl-(1 --> 4)-2-azido-3,6-di-O benzyl-2-deoxy-D-glucopyranosyl]-(1 --> 6)-2,3,4,5-tetra-O-benzyl-1-O-(4-methoxybenzyl)-D-myo-inositol, O-(2,3,4,6-tetra-O-benzyl-alpha-D-galactopyranosyl)-(1 --> 6)-2,3,4-tri-O-benzy]-D-galactopyranosyl fluoride, 2-O-acetyl-3,4,6-tri-O-benzyl-alpha-D-mannopyranosyl chloride, and 6-O-acetyl-2,3,4-tri-O-benzyl-alpha-D-mannopyranosyl fluoride. The introduction of two phosphodiester functions was efficiently achieved using the H-phosphonate method.