SYNTHESIS OF A PERIPHERAL TRISACCHARIDE SEQUENCE OF LUTROPIN, A PITUITARY GLYCOPROTEIN HORMONE - USE OF CHITOBIOSE AS A KEY STARTING MATERIAL

A chitobiose derivative, methyl O-(3,4,6-tri-O-acetyl-2-deoxy-2-phthalimido-β-d-glucopyranosyl)-(1→4)-3,6-di-O-acetyl-2-deoxy-2-phthalimido-β-d- glucopyranoside, was derived from the corresponding N-acetyl derivative and this was converted into the glycosyl bromide (5). Glycosidation reaction between 5 and methyl 3,4,6-tri-O-benzyl-α-d-mannopyranoside in the presence of silver trifluoromethanesulfonate gave a β-d-linked trisaccharide derivative. Replacement of the N,N-phthaloyl group by acetyl groups resulted in a product that was converted into methyl O-(2-acetamido-3,6-di-O-benzyl-2-deoxy-β-d-glucopyranosyl)-(1→4)-O-(2-acetamido-3,6-di-O-benzyl-2-deoxy-β-d- glucopyranosyl)-(1→2)-3,4,6-tri-O-benzyl-α-d-mannopyranoside (11) by use of a few reaction steps. The 43-hydroxyl group of 11 was methanesulfonylated, and the product subjected to SN2 replacement with acetate anion, to give the d-galactosamine-containing trisaccharide derivative (12). After basic hydrolysis of 12, the 43-hydroxyl group was sulfated, and all benzyl groups were removed by hydrogenolysis, giving methyl O-(2-acetamido-2-deoxy-4-O-sulfo-β-d-galactopyranosyl)-(1→4)-O-(2-acetamido-2-deoxy-β-d-glucopyranosyl)-(1→2)-α-d- mannopyranoside monosodium salt, the methyl α-glucoside derivative of the peripheral trisaccharide sequence of the pituitary glycoprotein hormone lutropin. © 1990.