SYNTHESIS OF A HEXADECASACCHARIDE FRAGMENT OF THE O-POLYSACCHARIDE OF SHIGELLA-DYSENTERIAE TYPE-1

A synthetic route is described to a hexadecasaccharide fragment of the O-polysaccharide portion of the lipopolysaccharide of Shigella dysenteriae type 1, a Gram-negative human pathogen. The key intermediate was a trichloroacetimidate derivative of the tetrasaccharide Rha alpha 1-->2Gal alpha 1-->3GlcNAc alpha 1-->3Rha alpha 1-->3 (23) which corresponds to a complete repeating unit of this polysaccharide. Important stages involved the stereoselective construction of a GlcNAc alpha 1-->3Rha synthon (7) which was transformed into a glycosyl acceptor (13) that was alpha-galactosylated in a stereocontrolled reaction with a thiogalactoside donor (14). Conversion of the Gal alpha 1-->3GlcNAc alpha 1-->3Rha intermediate 15 into the glycosyl acceptor 17 followed by stereoselective alpha-rhamnosylation afforded the fully protected tetrasaccharide glycoside from which the tetrasaccharide donor 23 was prepared that contains a selectively removable, benzyl protecting group at the site of the chain extension. The donor was first coupled with 1-decanol to give the tetrasaccharide glycoside 24. One-step conversion provided the tetrasaccharide acceptor 25. Subsequent, iterative glycosylations with the donor 23, used in excess, afforded the fully protected octa-, dodeca-, and hexadecasaccharides, conventional deprotection of which led to di- (2), tri- (3), and tetrameric (4) repeating units of the O-polysaccharide of Sh. dysenteriae type 1.