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

Abstract

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