The pseudosymmetric relationship of the bacterial sialic acid, pseudaminic acid, and 3-deoxy-D-manno-oct-2-ulosonic acid (KDO) affords the hypothesis that suitably protected KDO donors will adopt the trans, gauche conformation of their side chain and consequently be highly equatorially selective in their coupling reactions conducted at low temperature. This hypothesis is borne out by the synthesis, conformational analysis, and excellent equatorial selectivity seen on coupling of per-O-acetyl or benzylprotected KDO donors in dichloromethane at −78 °C. Mechanistic understanding of glycosylation reactions is advancing to a stage at which predictions of selectivity can be made. In this instance, predictions of selectivity provide the first highly selective entry into KDO equatorial glycosides such as are found in the capsular polysaccharides of numerous pathogenic bacteria.

We describe the synthesis of the unusual bicyclic sugar bradyrhizose in 14 steps and 6% overall yield from D-glucose. The synthesis involves the elaboration of a trans-fused carbocyclic ring onto the pre-existing glucopyranose framework followed by adjustment of the oxidation levels. Key steps include radical extension of the glucopyranose side chain, ring closing metathesis, allylic oxidation, Luche reduction, hydroxy-directed epoxidation and acid-catalyzed epoxide opening at the more substituted position.