Alternative syntheses and related n.m.r. studies of precursors for internal beta-D-galactopyranosyl residues in oligosaccharides, allowing chain extension at O-4.
Crystalline 2,3,6-tri-O-benzoyl-4-O-(bromoacetyl)-alpha-D-galactopyranosyl chloride (5) was prepared from methyl 2,3,6-tri-O-benzoyl-4-O-(bromoacetyl)-alpha- or -beta-D-galactopyranoside by cleavage with dichloromethyl methyl ether (DCMME) in the presence of zinc chloride. Silver trifluoromethanesulfonate (triflate) condensation of 5 with methyl 2,3,6-tri-O-benzoyl-beta-D-galactopyranoside gave the corresponding beta-linked disaccharide, which was O-de(bromoacetyl)ated and the resulting disaccharide nucleophile condensed with 5. The beta-linked trisaccharide obtained was deprotected, to give the methyl beta-glycoside of (1----4)-beta-linked D-galactotriose. Compound 5 was converted in high yield into the corresponding 1-O-beta-acetyl derivative, which was O-de(bromoacetyl)ated with thiourea to afford crystalline 1-O-acetyl-2,3,6-tri-O-benzoyl-beta-D-galactopyranose (9). Condensation of 9 with 5 yielded O-[2,3,6-tri-O-benzoyl-4-O-(bromoacetyl)-beta-D- galactopyranosyl]-(1----4)-1-O-acetyl-2,3,6-tri-O-benzoyl-beta-D- galactopyranose (17), which was cleaved with DCMME to give the corresponding glycosyl chloride (20). The same sequence of reactions involving 1,2,3,6-tetra-O-benzoyl-alpha-D-galactopyranose and 2,3,4,6-tetra-O-benzoyl-alpha-D-galactopyranosyl bromide afforded O-(2,3,4,6-tetra-O-benzoyl-beta-D-galactopyranosyl)-(1----4)-2,3,6-tri-O - benzoyl-alpha-D-galactopyranosyl chloride, which can be used to construct in an oligosaccharide the terminal, beta-linked (1----4)-beta-D-galactobiosyl group. Compounds 5, 17, and 20, when used as glycosyl donors, allow further chain extension at O-4 of the (terminal) beta-D-galactopyranosyl group. The structures of all mono- and di-saccharide intermediates, including those of orthoesters formed during glycosylations under neutral conditions, were confirmed by combination of homo- and hetero-nuclear-correlation n.m.r. experiments. The sites of glycosidic linkages in orthoesters were directly determined by 1 D INAPT n.m.r. experiments. Characteristic features of the 1H- and 13C-n.m.r. spectra of orthoesters which distinguish them from the corresponding oligosaccharides have been summarized.
Kovác
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NIDDK, National Institutes of Health, Bethesda, MD 20892.
Taylor
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D002236:Carbohydrate Conformation; D005690:Galactose; D007202:Indicators and Reagents; D007536:Isomerism; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D009844:Oligosaccharides / Q000138:chemical synthesis*; D013329:Structure-Activity Relationship
D007202:Indicators and Reagents; D009844:Oligosaccharides; D005690:Galactose