Synthesis of a peripheral trisaccharide sequence of lutropin, a pituitary glycoprotein hormone; use of chitobiose as a key starting material

• Published in: Carbohydrate research 1990-10, Vol.206 (2), p.207-217
• Main Authors: Nishimura, Shin-Ichiro, Kuzuhara, Hiroyoshi
• Format: Article
• Language: English
• Subjects: Carbohydrate Sequence; Carbohydrates with 4, 5, 6, ... C atoms, dissacharides and oligosaccharides; Carbohydrates. Nucleosides and nucleotides; Chemistry; Disaccharides; Exact sciences and technology; Glucans; Luteinizing Hormone - chemistry; Methods; Molecular Sequence Data; Molecular Structure; Organic chemistry; Preparations and properties; Trisaccharides - chemical synthesis; Trisaccharides - chemistry
• ISSN: 0008-6215; 1873-426X
• DOI: 10.1016/0008-6215(90)80061-7

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 4 3-hydroxyl group of 11 was methanesulfonylated, and the product subjected to S N2 replacement with acetate anion, to give the d-galactosamine-containing trisaccharide derivative ( 12). After basic hydrolysis of 12, the 4 3-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.