Synthesis of 2-acetamido-2-deoxy-4-O-(2-O-methyl-beta-D-galactopyranosyl)- D-glucopyranose (N-acetyl-2'-O-methyllactosamine).
1,3,4,6-Tetra-O-acetyl-2-O-methyl-D-galactopyranose, prepared from known methyl 6-O-acetyl-3,4-O-isopropylidene-beta-D-galactopyranoside, was treated with hydrogen bromide in dichloromethane to afford 3,4,6-tri-O-acetl-2-O-methyl-alpha-D-galactopyranosyl bromide. Condensation with benzyl 2-acetamido-3,6-di-O-benzyl-2-deoxy-alpha-D-glucopyranoside in acetonitrile in the presence of mercuric cyanide gave an approximately 1:1 mixture of benzyl 2-acetamido-3, 6-di-O-benzyl-2-deoxy-4-O-(3,4,6-tri-O-acetyl-2-O-methyl-beta- (8) and -alpha-D-galactopyranosyl)-alpha-D-glucopyranoside. O-Deacetylation and catalytic hydrogenolysis of the benzyl group furnished 2-acetamido-2-deoxy-4-O-(2-O-methyl-beta- and alpha-D-galactopyranosyl)-D-glucopyranose. Alternatively, benzyl 2-acetamido-3,6-di-O-benzyl-2-deoxy-4-O-beta-D- galactopyranosyl-alpha-D-glucopyranoside was treated with tert-butyldiphenyl-chlorosilane in N,N-dimethylformamide, in the presence of imidazole, to give a 6'-O-tert-butyldiphenylsilyl intermediate that was in turn converted into its 3',4'-O-isopropylidene acetal. Methylation with methyl iodide-silver oxide in N,N-dimethylformamide, followed by removal of the silyl and isopropylidene groups gave benzyl 2-acetamido-3,6-di-O-benzyl-2-deoxy-4-O-(2-O-methyl-beta-D- galactopyranosyl)-alpha-D-glucopyranoside, which was further characterized as its triacetate 8.
Department of Gynecologic Oncology, Roswell Park Memorial Institute, New York State Department of Health, Buffalo 14263.
S A
SA
Abbas
C F
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Piskorz
K L
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Matta
D000606:Amino Sugars / Q000138:chemical synthesis*; D002236:Carbohydrate Conformation; D007202:Indicators and Reagents; D009904:Optical Rotation; D013329:Structure-Activity Relationship
D000606:Amino Sugars; D007202:Indicators and Reagents; C048138:N-acetyl-2'-O-methyllactosamine