Synthesis of three tetrasaccharides containing 3-O-methyl-D-mannose, as model compounds for xylose-containing carbohydrate chains from N-glycoproteins.
The synthesis is reported of methyl 3,6-di-O-(3-O-methyl-alpha-D-mannopyranosyl)-2-O-beta-D-xylopyranosyl-be ta-D- mannopyranoside (2), methyl 6-O-alpha-D-mannopyranosyl-3-O-(3-O-methyl-alpha-D-mannopyranosyl)-2-O-b eta-D- xylopyranosyl-beta-D-mannopyranoside (3), and methyl 3-O-alpha-D-mannopyranosyl-6-O-(3-O-methyl-alpha-D-mannopyranosyl)-2-O-b eta-D- xylopyranosyl-beta-D-mannopyranoside (4). The various methyl beta-D-Manp acceptor derivatives were prepared from the corresponding methyl beta-D-Glcp derivatives via oxidation-reduction. All glycosyl donors were coupled using the trichloroacetimidate method at -40 degrees C in dichloromethane with trimethylsilyl triflate as a catalyst. Methyl-3-O-benzyl-4,6-O-benzylidene-beta-D-mannopyranoside (7) was condensed with 2,3,4-tri-O-acetyl-alpha-D-xylopyranosyl trichloroacetimidate (8). Regioselective reductive 4,6-O-benzylidene ring-opening on the resulting disaccharide derivative, followed by acetylation, and hydrogenation gave methyl 4-O-acetyl-2-O-(2,3,4-tri-O-acetyl-beta-D-xylopyranosyl)-beta-D-mannopyr anoside (12). Coupling of 12 with 2,4,6-tri-O-acetyl-3-O-methyl-alpha-D-mannopyranosyl trichloroacetimidate (18) afforded tetrasaccharide derivative 19, and subsequent O-deacetylation gave 2. Methyl 3-O-benzyl-4,6-O-prop-2-enylidene-beta-D-mannopyranoside (22) was condensed with 2,3,4-tri-O-acetyl-alpha-D-xylopyranosyl trichloroacetimidate (8). Regioselective reductive 4,6-O-prop-2-enylidene ring-opening on the resulting disaccharide derivative, followed by acetylation, and deallylation at O-6 gave methyl 4-O-acetyl-3-O-benzyl-2-O-(2,3,4-tri-O-acetyl-beta-D-xylopyranosyl)-beta -D- mannopyranoside (26-a), which was either condensed with 2,3,4,6-tetra-O-acetyl-alpha-D-mannopyranosyl trichloroacetimidate (27) or 18, to give trisaccharide derivatives 28 or 31, respectively. Debenzylation of 28 followed by condensation with 18 gave, after O-deacetylation, 3, whereas debenzylation of 31 followed by condensation with 27 gave, after O-deacetylation, 4.
van der Ven
J G
JG
Bijvoet Center, Department of Bio-Organic Chemistry, Utrecht University, Netherlands.
Wijkmans
J C
JC
Kamerling
J P
JP
Vliegenthart
J F
JF
D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D006023:Glycoproteins / Q000737:chemistry*; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D008766:Methylmannosides; D008956:Models, Chemical; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009844:Oligosaccharides / Q000138:chemical synthesis* / Q000737:chemistry; D009904:Optical Rotation; D014994:Xylose
D006023:Glycoproteins; D007202:Indicators and Reagents; D008766:Methylmannosides; D009844:Oligosaccharides; C043123:3-O-methylmannose; D014994:Xylose