Mimics of the structural elements of type III group B Streptococcus capsular polysaccharide .1. Synthesis of a carboxylate-containing pentasaccharide

A carboxylate-containing pentasaccharide, methyl O-(beta-D-galactopyranosyl)-(1-->4)-O-(beta-D-glucopyranosyl)-(1-->6)-O-{3-O-[(S)-1-carboxyethyl]-beta-D-galactopyranosyl-(1-->4)-O}-(2-acetamido-2-deoxy-beta-D-glucopyranosyl)-(1-->3)-beta-D-galactopyranoside (27) was synthesized by block condensation of suitably protected donors and accepters. Phenyl 3-O-benzyl-4,6-di-O-chloroacetyl-2-deoxy-2-phthalimido-1-thio-beta-D-glucopyranoside (17) was condensed with methyl 2,4,6-tri-O-benzyl-beta-D-galactopyranoside (4) to afford a disaccharide, methyl O-(3-O-benzyl-4,6-di-O-chloroacetyl-2-deoxy-2-phthalimido-beta-D-glucopyranosyl)-(1-->3)-2,4,6-tri-O-benzyl-beta-D-galactopyranoside (18). Removal of chloroacetyl groups gave 4,6-diol, methyl O-(3-O-benzyl-2-deoxy-2-phthalimido-beta-D-glucopyranosyl)-(1-->3)-2,4,6-tri-O-benzyl-beta-D-galactopyranoside (19), in which the primary hydroxy group (6-OH) was then selectively chloroacetylated to give methyl O-(3-O-benzyl-6-O-chloroacetyl-2-deoxy-2-phthalimido-beta-D-glucopyranosyl)-(1-->3)-2,4,6-tri-O-benzyl-beta-D-galactopyranoside (20). This acceptor was then coupled with 2,4,6-tri-O-acetyl-3-O-[(S)-1-(methoxycarbonyl)ethyl]-alpha-D-galactopyranosyl trichloroacetimidate (14) to afford a trisaccharide, methyl O-{2,4,6-tri-O-acetyl-3-O-[(S)-1-(methoxycarbonyl)ethyl]-beta-D-galactopyranosyl}-(1-->4)-O-(3-O-benzyl-6-O-chloroacetyl-2-deoxy-2-phthalimido-beta-D-glucopyranosyl)-(1-->3)-2,4,6-tri-O-benzyl-beta-D-galactopyranoside (21). Removal of the 6-O-chloroacetyl group in 21 gave 22, which was coupled with 4-O-(2,3,4,6-tetra-O-acetyl-beta-D-galactopyranosyl)-2,3,6-tri-O-acetyl-alpha-D-glucopyranosyl trichloroacetimidate (23) to yield protected pentasaccharide 24. Standard procedures were used to remove acetyl groups and the phthalimido group, followed by N-acetylation, and debenzylation to yield pentasaccharide 27 and a hydrazide by-product (28) in a 5: 1 ratio, respectively. Compound 27 contains a complete repeating unit of the capsular polysaccharide of type III group B Streptococcus in which terminal sialic acid is replaced by an (S)-1-carboxyethyl group.