SYNTHESIS OF STRUCTURAL ELEMENTS OF THE CAPSULAR POLYSACCHARIDE OF STREPTOCOCCUS-PNEUMONIAE TYPE-8

The synthesis is reported of propyl 4-O-alpha-D-galactopyranosyl-beta-D-glucopyranosiduronic acid (25), 4-O-[4-O-(beta-D-glucopyranosyluronic acid)-beta-D-glucopyranosyl]-D-glucopyranose (34), and 4-O-(4-O-beta-D-glucopyranosyl-alpha-D-glucopyranosyl)-D-galactopyranose (38), each representing a structural element of the repeating unit of the capsular polysaccharide of Streptococcus pneumoniae type 8, [-->4)-beta-D-GlcpA-(1-->4)-beta-D-Glcp-(1-->4)-alpha-D-Glcp-(1-->4)-alpha-D-Galp-(1-->]n. 2,3-Di-O-benzyl-4,6-O-benzylidene-alpha-D-galactopyranosyl trichloroacetimidate (12) was coupled to allyl 2-0-acetyl-3-O-benzyl-6-0-trityl-beta-D-glucopyranoside (7) in dichloromethane-ether, using trimethylsilyl trifluoromethanesulfonate as a promoter, to give disaccharide derivative 20. Detritylation of 20, followed by oxidation and deprotection, afforded disaccharide propyl glycoside 25. Coupling of 2,3,4,6-tetra-0-acetyl-alpha-D-glucopyranosyl trichloroacetimidate (8) to allyl 2,3,6-tri-O-benzyl-4-O-(2,3,6-tri-O-benzyl-beta-D-glucopyranosyl)-beta-D-glucopyranoside (17) in dichloromethane, with trimethylsilyl trifluoromethanesulfonate as a promoter, resulted in trisaccharide derivative 26. Deacetylation of 26, followed by 6-O-tritylation, benzylation, detritylation, and oxidation gave a protected trisaccharide derivative (31), which, after deprotection, afforded 34. Coupling of allyl 2,3,6-tri-O-benzyl-beta-D-galactopyranoside (10) to 4-O-(2,3-di-O-benzyl-4,6-O-benzylidene-beta-D-glucopyranosyl)-2,3,6-tri-O-benzyl-D-glucopyranosyl trichloroacetimidate (19) in ether, with trimethylsilyl trifluoromethanesulfonate as a promoter, gave trisaccharide derivative 35. Deallylation of 35, followed by hydrogenolysis afforded 38.