The synthesis is reported of methyl O-β-d-galactopyranosyl-(1-4)-O-β-d-glucopyranosyl-(1-6)-O-[β-d-galactopyranosyl-(1-4)]-O-2-acetamido-2-deoxy-β-d-glucopyranoside (13), methyl O-β-d-galactopyranosyl-(1-4)-O-β-d-glucopyranosyl-(1-6)-O-[β-d-galactopyranosyl-(1-4)]-O-(2-acetamido-2-deoxy-β-d-glucopyranosyl)-(1-3)-O-β-d-galactopyranosyl-(1-4)-β-d-glucopyranoside (28), and O-β-d-galactopyranosyl-(1-4)-O-β-d-glucopyranosyl-(1-6)-O-[β-d-galactopyranosyl-(1-4)]-O-(2-acetamido-2-deoxy-β-d-glucopyranosyl)-(1-3)-O-β-d-galactopyranosyl-(1-4)-d-glucopyranose (38), representing fragments of the capsular polysaccharide of Streptococcus pneumoniae type 14 ({-3)-β-d-Galp-(1-4)-β-d-Glcp-(1-6)-[β-d-Galp-(1-4)]-β-d-GlcpNAc-(1-}n). 4-O-(2,3,4,6-Tetra-O-acetyl-β-d-galactopyranosyl)-2,3,6-tri-O-acetyl-α-d-glucopyranosyl trichloroacetimidate (6) was coupled regio- and stereoselectively with HO-6 of methyl 3-O-benzyl-2-deoxy-2-phthalimido-β-d-glucopyranoside (4) in dichloromethane, using boron trifluoroetherate as a promoter. Coupling of 2,3,4,6-tetra-O-acetyl-α-d-galactopyranosyl trichloroacetimidate (8) with HO-4 of the resulting trisaccharide derivative (9) in dichloromethane, using boron trifluoroetherate as a promoter, afforded methyl 4-O-(2,3,4,6-tetra-O-acetyl-β-d-galactopyranosyl)-6-O-[4-O-(2,3,4,6-tetra-O-acetyl-β-d-galactopyranosyl)-2,3,6-tri-O-acetyl-β-d-glucopyranosyl]-3-O-benzyl-2-deoxy-2-phthalimido-β-d-glucopyranoside (10). Debenzylation of 10, followed by dephthaloylation, N,O-acetylation, and de-O-acetylation gave tetrasaccharide methyl glycoside 13. Disaccharide derivative 6 was also coupled with HO-6 of allyl 3-O-benzyl-2-deoxy-2-phthalimido-β-d-glucopyranoside (16) in dichloromethane using trimethylsilyl trifluoromethanesulfonate as a promoter. Coupling of 8 with HO-4 of the resulting trisaccharide derivative (17) in dichloromethane, using trimethylsilyl trifluoromethanesulfonate as a promoter, afforded allyl 4-O-(2,3,4,6-tetra-O-acetyl-β-d-galactopyranosyl)-6-O-[4-O-(2,3,4,6-tetra-O-acetyl-β-d-galactopyranosyl)-2,3,6-tri-O-acetyl-β-d-glucopyranosyl]-3-O-benzyl-2-deoxy-2-phthalimido-β-d-glucopyranoside (18). Deallylation of 18, followed by imidation gave an activated tetrasaccharide (20), which was coupled to both methyl (24) and benzyl (33) 2,3,6-tri-O-benzyl-4-O-(2,4,6-tri-O-benzyl-β-d-galactopyranosyl)-β-d-glucopyranoside in dichloromethane, using trimethylsilyl trifluoromethanesulfonate as a promoter, to give the corresponding hexasaccharide derivatives 25 and 34. Debenzylation of 25, followed by dephthaloylation, N,O-acetylation, and de-O-acetylation gave hexasaccharide methyl glycoside 28. Dephthaloylation of 34, followed by N,O-acetylation, debenzylation, re-O-acetylation and de-O-acetylation gave hexasaccharide 38.
Publication DOI: 10.1080/07328309408009174Journal NLM ID: 8218151Publisher: Marcel Dekker
Institutions: Bijvoet Center, Department of Bio-Organic Chemistry, Utrecht University, Utrecht, The Netherlands
Methods: 13C NMR, 1H NMR
Found