Synthesis of the monosaccharide units of the O-specific polysaccharide of Shigella sonnei

The monosaccharide components of the O-specific polysaccharide 1 of the lipopolysaccharide of the enteropathogenic bacterium Shigella sonnei were synthesized as their methyl glycosides 2 and 3 in their natural anomeric form. The key intermediate to the diamino-trideoxygalactose derivative 2 was ethyl 3-O-acetyl-2-deoxy-2-phthalimido-1-thio-beta-D-glucopyranoside (9) that was converted to its ditosylate 10. Regioselective deoxygenation at C-6 followed by nucleophilic displacement of the secondary tosyloxy group by azide afforded the 4-azido thioglycoside 13. Methyl trifluoromethanesulfonate-assisted methanolysis of 13 gave the O-glycoside 14. Replacement of the phthalimido by an acetamido group followed by catalytic reduction of the azido group led to the diamino-trideoxygalactose derivative 2, The precursor to the L-altruronic acid derivative 3 was methyl alpha-L-glucopyranoside (19) that was routinely converted to the benzylidene-protected 2,3-anhydro-allopyranoside 22. Regioselective opening of the epoxide ring by NaN3 afforded the 2 azido derivative 23 that was benzylated at HO-3. Hydrolytic removal of the benzylidene group followed by TEMPO oxidation of C-6 and subsequent esterification with MeI gave the key L-azido-altruronic acid intermediate 29 that was transformed to the acetamido-altruronic acid derivative 3. High resolution NMR data of the altruronic acid derivatives indicate that the conformation of their pyranose ring is crucially dependent on the substitution pattern: the 2-azido altruronic acid derivatives prefer the C-4(1) conformation whereas the 2-acetamido congeners exist preferentially in the C-1(4) conformation.