Systematic chemical synthesis and n.m.r. spectra of methyl alpha-glycosides of isomalto-oligosaccharides and related compounds.
Acid-catalyzed thiophenolysis of 1,6-anhydro-2,3,4-tri-O-benzyl-beta-D-glucopyranose and acetylation of the resulting phenyl 2,3,4-tri-O-benzyl-1-thio-alpha-D-glucopyranoside (4) gave phenyl 6-O-acetyl-2,3,4-tri-O-benzyl-1-thio-alpha-D-glucopyranoside (5). Reaction of 5 with chlorine gave, stereospecifically, the corresponding beta-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-alpha-D-glucopyranosyl)-(1----6)-2,3,4- tri-O- benzyl-1-thio-alpha-D-glucopyranoside (17). Crystalline O-(6-O-acetyl-2,3,4-tri-O-benzyl-alpha-D-glucopyranosyl)-(1----6)-2,3,4- tri- O-benzyl-beta-D-glucopyranosyl chloride, readily obtainable in a stereo-specific manner from 17 by treatment with chlorine, was used as the key glycosyl (isomaltosyl) donor in the blockwise synthesis of methyl glycosides of isomalto-oligosaccharides, up to and including the octasaccharide. The methyl alpha-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-alpha,beta-D-glucopyranosyl fluoride as the glycosyl donor, a suitably protected methyl alpha-isomaltotrioside as the nucleophile, and silver perchlorate as the promoter. The n.m.r. spectra (1H- and 13C-) of numerous 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 beta-glycosyl chlorides were high-yielding and showed high stereo-selectivity for the formation of an alpha-(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.
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National Institutes of Health, Bethesda, Maryland 20892.
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D002236:Carbohydrate Conformation; D006027:Glycosides; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D008745:Methylation; D008759:Methylglycosides / Q000138:chemical synthesis*; D009844:Oligosaccharides / Q000138:chemical synthesis*; D009904:Optical Rotation; D013329:Structure-Activity Relationship
D006027:Glycosides; D007202:Indicators and Reagents; D008759:Methylglycosides; D009844:Oligosaccharides; C021705:maltooligosaccharides