Chemoenzymatic Synthesis of Common Legionaminic Acid−Containing Pentasaccharide of Capsular Polysaccharides from <i>Acinetobacter baumannii</i><scp>K27</scp> and <scp>K44</scp>^†

Comprehensive Summary Acinetobacter baumannii infections pose a great threat to public health owing to upsurging antibiotic resistance. Capsular polysaccharides (CPS) are major virulence determinants of pathogenic bacteria and have attracted much attention as potential targets for vaccine development. However, the obtainability of structurally well‐defined CPS‐related oligosaccharides remains challenging. Herein, we report an efficient chemoenzymatic strategy for the first total synthesis of common CPS pentasaccharide repeating unit of Acinetobacter baumannii K27 and K44, containing a difficult‐to‐construct α‐linked 5,7‐di‐ N ‐acetyllegionaminic acid (Leg5,7Ac 2 ) residue. The chemical synthesis of a branched tetrasaccharide precursor was accomplished by flexible orthogonal protecting‐group manipulations and stereocontrolled glycosylations. Furthermore, the enzyme‐catalyzed stereoselective installment of legionaminic acid residue into the tetrasaccharide, using one‐pot multienzyme (OPME) synthesis system to produce sugar nucleotide CMP‐Leg5,7diN 3 and subsequent α2,6‐sialyltransferase‐catalyzed glycosylation, was achieved to synthesize the pentasaccharide.