Stereocontrolled Synthesis of a Heptose- and Kdo-Containing Common Inner-Core Trisaccharide of Lipopolysaccharides from Multiple Pathogenic Bacteria

Abstract

Lipopolysaccharides (LPSs) are major virulence determinants in Gram-negative bacteria and are responsible for many pathophysiological processes during bacterial infections. However, the accessibility of LPS-associated oligosaccharides for infectious mechanism study and vaccine development remains challenging. We report an efficient stereocontrolled approach for the synthesis of a common inner-core trisaccharide containing difficult-to-access, rare, higher-carbon sugars: a heptose (Hep) and 3-deoxy-α-d-manno-oct-2-ulosonic acid (Kdo). Key features include comprehensive elaboration of a practical synthesis of versatile Hep and Kdo building blocks, and stereoselective assembly of an inner-core trisaccharide from multiple pathogenic bacteria.