A facile synthesis of 2-acetamido-2-deoxy-4-O-α-l-fucopyranosyl-3-O-β-d-galactopyranosyl-d-glucopyranose, the Lewis a blood-group antigenic determinant, and related compounds

A simple strategy was developed for the procurement of benzyl 2-acetamido-6-O-benzyl-2-deoxy-3-O-(2,3,4,6-tetra-O-acetyl-β-d-galactopyranosyl)-β-d-gluco-pyranoside (8). Reductive opening of the acetal ring of benzyl 2-acetamido-4,6-O-benzylidene-2-deoxy-3-O-(2,3,4,6-tetra-O-acetyl-β-d-galactopyranosyl)-β-d-gluco-pyranoside gave, exclusively, the desired, key intermediate 8. Fucosylation of 8 with 2,3,4-tri-O-benzyl-α-l-fucopyranosyl bromide, under catalysis by bromide ion, afforded the trisaccharide derivative which, on O-deacetylation, followed by hydrogenolysis, produced the title trisaccharide. Starting from methyl 2-acetamido-4,6-O-benzylidene-2-deoxy-3-O-(2,3,4,6-tetra-O-acetyl-β-d-galactopyranosyl)-α-d-glucopyranoside, the synthesis of methyl 2-acetamido-2-deoxy-4-O-α-l-fucopyranosyl-3-O-β-d-galactopyranosyl-α-d-glucopyranoside was accomplished by a similar reaction-sequence. The synthesis of 2-acetamido-2-deoxy-4-O-α-l-fucopyranosyl-d-glucopyranose is also described. The structures of the final saccharides, and of various other intermediates, were established by ¹H- and ¹³C-n.m.r. spectroscopy.