ИСТИНА

The A and B antigens are present on the surface of blood cells and on cells in various tissues and organs throughout the human body and in secretions. The studies of their function require these oligosaccharides in amounts, which can not be obtained from natural sources. We have developed a new efficient method for block synthesis of B (type 1, type 2) tetrasaccharides as aminopropyl glycosides using block scheme [3+1]. Herein “3” is B trisaccharide glycosyl donor and “1” is a suitable derivative of glucosamine. Available B trisaccharide aminopropyl glycoside [1] was chosen as the glycosyl donor precursor. Acetylation and acid-catalysed acetolysis gave peracetylated trisaccharide, which was easily converted to glycosyl trichloroacetimidate. (3-Trifluoroacetamidopropyl)-2-acetamido-4,6-O-benzyliden-2-deoxy-β-D-glucopyranoside (I) was used as mono-OH glycosyl acceptor for the synthesis of type 1 tetrasaccharide. (3-Trifluoroacetamidopropyl)-2-acetamido-3-O-acetyl-6-O-benzyl-2-deoxy-β-D-glucopyranoside (II) and 2-acetamido-1,6-anhydro-3-О-benzoyl-2-deoxy-β-D-glucopyranoside (III) were chosen as glycosyl acceptors for type 2 tetrasaccharide. Also (3-trifluoroacetamidopropyl)-2-acetamido-6-O-benzyl-2-deoxy-β-D-glucopyranoside (IV) was tested as a glycosyl acceptor, which possesses reactive 3-OH and 4-OH groups potentially giving rise to type 1 and 2 tetrasaccharides. Glycosylation of I with B trisaccharide trichloroacetimidate was carried out in CH3CN with the use of TMSOTf as the promoter to provide high β-stereoselectivity and good yield. Glycosylation of (IV) gave only one product, B (type 1) tetrasaccharide. Glycosylation of II by B trisaccharide trichloroacetimidate did not give the desired oligosaccharide. The derivative (III) was glycosylated by B trisaccharide glycosyl trichloroacetimidate in CH3CN or CH3CN–CH2Cl2 mixture in the presence of catalytic amount of TMSOTf. It was found that addition of CH2Cl2 led to increase of total tetrasaccharide yield and to lower β-stereoselectivity. The obtained 1,6-anhydro derivative of B tetrasaccharide was subjected to acid-catalyzed acetolysis, selective 1-O-deacetylation, and treatment with MsCl and symm. collidine. The obtained oxazoline was spacer-armed with 3-trifluoroacetamidopropanol. Deprotection by usual methods gave required tetrasaccharides with good yields. [1] E.Yu.Korchagina, N.V.Bovin. Synthesis of spacered trisaccharides with blood group specificities A and B, their fragments and structural analogs. Bioorgan. Khim., 18, 283-298 (1992).