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-deo xy- alpha-D-glucopyranosyl)-(1-->6)-[1-O-(1,2-dimyristoyl-sn-glycero-3-phosp hono) - 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-be nzyl- 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- benzyl-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.