title: Selective bromoacetylation of alkyl hexopyranosides: a facile preparation of intermediates for the synthesis of (1----6)-linked oligosaccharides.
abstract: Bromoacetylation of methyl beta-D-galacto- (1), alpha-D-galacto- (6), beta-D-gluco- (18), (22), and alpha-D-manno-pyranoside (31), and benzyl beta-D-glucopyranoside (27), gave the corresponding 6-O-bromoacetyl derivatives 2, 7, 19, 23, 32, and 28 in 50-60% yields. Bromoacetylation of methyl 3-O-benzyl-beta-D-galactopyranoside (11) afforded methyl 3-O-benzyl-6-O-bromoacetyl-beta-D-galactopyranoside (12, 60%) as well as methyl 3-O-benzyl-2,6-di-O-bromoacetyl-beta-D-galactopyranoside (13, 14%). Compounds 2, 7, 19, 23, 32, 28, and 12 were benzoylated and the fully protected derivatives obtained were dehaloacetylated with thiourea to afford the methyl 2,3,4-tri-O-benzoyl-D-glycopyranosides of beta-galactose (5), alpha-galactose (9), beta-glucose (21), alpha-glucose (25), and alpha-mannose (34), as well as benzyl 2,3,4-tri-O-benzoyl-beta-D-glucopyranoside (30) and methyl 3-O-benzyl-2,4-di-O-benzoyl-beta-D-galactopyranoside (15). These compounds can be used as nucleophiles for the synthesis of (1----6)-linked oligosaccharides. The conversion 1----5 could be performed without isolation of the intermediates. The treatment of bromoacetyl derivatives with benzoyl chloride in pyridine resulted in the benzoylation of the remaining free hydroxyl groups and the simultaneous substitution of bromine by chlorine, yielding the corresponding mono-O-chloroacetyl derivatives. Benzoylations with benzoyl bromide avoided this secondary event. Glycosyl donors differentially substituted to allow further extension of the oligosaccharide chain at position 6 of D-glucose, D-galactose, and D-mannose, and sequentially at positions 6 and 3 in the case of the D-galactosyl donor derived from 15, were readily obtained by treatment of the appropriate, fully protected methyl glycosides with 1,1-dichloromethyl methyl ether in the presence of a catalytic amount of zinc chloride.
authors.affiliation: NIDDK, National Institutes of Health, Bethesda, MD 20892.
authors.forename: T
authors.initials: T
authors.lastname: Ziegler
authors.forename: P
authors.initials: P
authors.lastname: Kovác
authors.forename: C P
authors.initials: CP
authors.lastname: Glaudemans
mesh_terms: D000107:Acetylation; D000478:Alkylation; D001966:Bromine; D002236:Carbohydrate Conformation; D006027:Glycosides; D007202:Indicators and Reagents; D009844:Oligosaccharides / Q000138:chemical synthesis*; D009904:Optical Rotation
chemical_list: D006027:Glycosides; D007202:Indicators and Reagents; D009844:Oligosaccharides; D001966:Bromine