Synthesis of 6-deoxy-d-ido-heptopyranose-containing fragments of the Campylobacter jejuni strain CG8486 capsular polysaccharide.

Campylobacters are important causes of gastrointestinal illness and the capsular polysaccharides (CPS) they produce are key virulence factors and targets for vaccine development. We report here the synthesis of two fragments of the Campylobacter jejuni CG8486 strain CPS that contain a rare 6-deoxy-d-ido-heptopyranose residue and, in one target, two O-methyl phosphoramidate (MeOPN) motifs. The synthetic approach features the stereoselective construction of the ß-d-ido-heptopyranoside linkage via glycosylation with a ß-d-galacto-heptopyranoside donor followed by a one-pot sequential C-2 and C-3 inversion. During the syntheses, we uncovered a number of interesting conformational effects with regard to the 6-deoxy-ido-heptopyranose ring, the glycosidic linkage connecting the two monosaccharides, and the MeOPN groups.

One-Pot Regioselective Diacylation of Pyranoside 1,2-cis Diols.

A one-pot strategy for functionalizing pyranoside 1,2-cis-diols with two different ester protecting groups is reported. The approach employs regioselective acylation via orthoester hydrolysis promoted by a carboxylic acid, e.g., levulinic acid, acetic acid, benzoic acid, or chloroacetic acid. Upon removal of water and introduction of a coupling agent, the carboxylic acid is esterified to the hydroxyl group liberated during hydrolysis. Although applied to 1,2-cis-diols on pyranoside scaffolds, the method should be applicable to such motifs on any six-membered ring.

Synthesis of the Campylobacter jejuni 81-176 Strain Capsular Polysaccharide Repeating Unit Reveals the Absolute Configuration of its O-Methyl Phosphoramidate Motif.

The O-methyl phosphoramidate (MeOPN) motif is a non-stoichiometric modification of capsular polysaccharides (CPS) in ≈70 % of all Campylobacter jejuni strains. Infections by C. jejuni lead to food-borne illnesses and the CPS they produce are key virulence factors. The MeOPN phosphorus atom in these CPS is stereogenic and is found as a single stereoisomer. However, to date, the absolute stereochemistry at this atom has been undefined. We report the synthesis of the three repeating units found in C. jejuni 81-176 CPS; one of these possesses a MeOPN group. In the course of these studies we established that the stereochemistry of the phosphorus atom in this MeOPN group is R. These studies represent the first unequivocal proof of stereochemistry of this group in any C. jejuni CPS. The compounds produced are anticipated to be useful tools in investigations targeting the function and biosynthesis of this structurally-interesting modification, which so far has only been identified in campylobacter.

Synthesis of a C-glycoside analogue of ß-galactosyl ceramide, a potential HIV-1 entry inhibitor.

A ß-C-galactosyl ceramide was synthesized in a stereoselective manner, employing a Sharpless AD reaction and olefin cross metathesis as key steps.

Synthesis of ß-C-galactosyl D- and L-alanines.

Synthesis of ß-C-D-galactosyl D- and L-alanines is carried out via a highly stereoselective Grignard reaction of glycosyl iodides, Sharpless dihydroxylation and S(N)2 displacement of the corresponding mesylate or tosylate. Alternatively, attempted triflation of the intermediate alcohols triggers a stereoselective debenzylative cyclization leading to interesting bicyclic trans-fused compounds.