SYSTEMATIC CHEMICAL SYNTHESIS AND N.M.R. SPECTRA OF METHYL α-GLYCOSIDES OF ISOMALTO-OLIGOSACCHARIDES AND RELATED COMPOUNDS

Article abstract of DOI:10.1016/0008-6215(88)80008-9

Acid-catalyzed thiophenolysis of 1,6-anhydro-2,3,4-tri-O-benzyl-β-D-glucopyranose and acetylation of the resulting phenyl 2,3,4-tri-O-benzyl-1-thio-α-D-glucopyranoside (4) gave phenyl 6-O-acetyl-2,3,4-tri-O-benzyl-1-thio-α-D-glucopyranoside (5).Reaction of 5 with chlorine gave, stereospecifically, the corresponding β-glycosyl chloride, which was treated with 4 in the presence of silver perchlorate and 2,4,6-trimethylpyridine to afford phenyl O-(6-O-acetyl-2,3,4-tri-O-benzyl-α-D-glucopyranosyl)-(1->6)-2,3,4-tri-O-benzyl-1-thio-α-D-glucopyranoside (17).Crystalline O-(6-O-acetyl-2,3,4-tri-O-benzyl-α-D- glucopyranosyl)-(1->6)-2,3,4-tri-O-benzyl-β-D-glucopyranosyl chloride, readily obtainable in a stereospecific manner from 17 by treatment with chlorine, was used as the key glycosyl (isomaltosyl) donor in the bockwise synthesis of methyl glycosides of isomalto-oligosaccharides, up to and including the octasaccharide.The methyl α-glycoside of isomaltotetraose fluorinated at C-6 of the terminal D glucopyranosyl group was prepared by using SnCl2-activated 2,3,4-tri-O-benzyl-6-deoxy-6-fluoro-α,β-D-glucopyranosyl fluoride as the glycosyl donor, a suitably protected methyl α-isomaltotrioside as the nucleophile, and silver perchlorate as the promoter.The n.m.r. spectra (1H- and 13C-) of numereous synthetic intermediates were analyzed and completely assigned by a variety of two-dimensional homo- and hetero-nuclear n.m.r.-spectroscopic techniques, and the final deprotected title oligosaccharides were characterized by 13C-n.m.r. data.Silver perchlorate-mediated glycosylation reactions involving β-glycosyl chlorides were high-yielding and showed high stereoselectivity for the formation of an α-(cis)-glycosidic linkage.The practical limitation of obtaining high isomalto-oligosaccharides in this way appears to lie solely in the separation technique applied for the resolution of the crude products formed.