Synthesis of the methyl glycosides of a di- and two trisaccharide fragments specific for the Shigella flexneri serotype 2a O-antigen

The stereocontrolled synthesis of methyl alpha-D-glucopyranosyl-(1-->4)-alp ha-L-rhamnopyranoside (EC, 1), methyl alpha-L-rhamnopyranosyl-(1-->3)-[alph a-D-glucopyra- osyl-(1-->4)]-alpha-L-rhamnopyranoside (B(E)C, 3) and methyl alpha-D-glucopyranosyl-(1-->4)-alpha-L-rhamnopyranosyl-(1-->3)-2-acetamido -2-deoxy-beta-D-glucopyranoside (ECD, 4) is described; these constitute the methyl glycosides of branched and linear fragments of the O-specific polys accharide of Shigella flexneri serotype 2a. Emphasis was put on the constru ction of the 1,2-cis EC glycosidic linkage resulting in the selection of 2, 3,4,6-tetra-O-benzyl-alpha-D-glucopyranosyl fluoride (8) as the donor. Cond ensation of methyl 2,3-O-isopropylidene-4-O-trimethylsilyloside-alpha-L-rha mnopyranoside (11) and 8 afforded the fully protected alpha E-disaccharide 20, as a common intermediate in the synthesis of 1 and 3, together with the corresponding beta E-anomer 21. Deacetalation and regioselective benzoylat ion of 20, followed by glycosylation with 2,3,4-tri-O-benzoyl-alpha-L-rhamn opyranosyl trichloroacetimidate (15) afforded the branched trisaccharide 25 . Full deprotection of 20 and 25 afforded the targets 1 and 3, respectively . The corresponding beta E-disaccharide, namely, methyl beta-D-glucopyranos yl-(1-->4)-a-L-rhamnopyranoside (PEC, 2) was prepared analogously from 21. Two routes to trisaccharide 4 were considered. Route 1 involved the couplin g of a precursor to residue E and a disaccharide CD. Route 2 was based on t he condensation of an appropriate EC donor and a precursor to residue D. Th e former route afforded a 1:2 mixture of the alpha E and PE condensation pr oducts which could not be separated, neither at this stage, nor after deace talation. In route 2, the required alpha E-anomer was isolated at the disac charide stage and transformed into 2,3,4,6-tetra-O-benzyl-alpha-D-glucopyra nosyl-(1-->4)-2,3-di-O-benzoyl-alpha-L-rhamnopyranosyl trichloroacetimidate (48) as the EC donor. Methyl 2-acetamido-2-deoxy-4,6-O-isopropylidene-beta -D-glucopyran-oside (19) was preferred to its benzylidene analogue as the p recursor to residue D. Condensation of 19 and 48 and stepwise deprotection of the glycosylation product afforded the target 4.