Azide‐Functionalized Derivatives of the Virulence‐Associated Sugar Pseudaminic Acid: Chiral Pool Synthesis and Labeling of Bacteria

• Published in: Chemistry : a European journal Vol. 27; no. 41; pp. 10595 - 10600
• Main Authors: Vibhute, Amol M., Tamai, Hideki, Logviniuk, Dana, Jones, Peter G., Fridman, Micha, Werz, Daniel B.
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 21.07.2021; Wiley Subscription Services, Inc; John Wiley and Sons Inc
• Subjects: azidoacetamide; Bacteria; Cell surface; Chemistry; Chemistry, Multidisciplinary; chiral pool; Elongation; Glycoproteins; Labeling; metabolic labeling; Metabolism; Monosaccharides; Physical Sciences; Polysaccharides; pseudaminic acid; Reagents; Science & Technology; Strains (organisms); Synthesis; Virulence; CAPSULAR POLYSACCHARIDE; LEGIONAMINIC ACID; bacteria; PATHWAY; pseudaminic acid; PSEUDOMONAS-AERUGINOSA; BIOSYNTHESIS; LIPOPOLYSACCHARIDE; metabolic labeling; azidoacetamide; chiral pool
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.202100443

Pseudaminic acid (Pse) is a significant prokaryotic monosaccharide found in important Gram‐negative and Gram‐positive bacteria. This unique sugar serves as a component of cell‐surface‐associated glycans or glycoproteins and is associated with their virulence. We report the synthesis of azidoacetamido‐functionalized Pse derivatives as part of a search for Pse‐derived metabolic labeling reagents. The synthesis was initiated with d‐glucose (Glc), which served as a cost‐effective chiral pool starting material. Key synthetic steps involve the conversion of C1 of Glc into the terminal methyl group of Pse, and inverting deoxyaminations at C3 and C5 of Glc followed by backbone elongation with a three‐carbon unit using the Barbier reaction. Metabolic labeling experiments revealed that, of the four Pse derivatives, ester‐protected C5 azidoacetamido‐Pse successfully labeled cells of Pse‐expressing Gram‐positive and Gram‐negative strains. No labeling was observed in cells of non‐Pse‐expressing strains. The ester‐protected and C5 azidoacetamido‐functionalized Pse is thus a useful reagent for the identification of bacteria expressing this unique virulence‐associated nonulosonic acid. Tailor‐made derivatives of pseudaminic acid (Pse) allow for the detection of Gram‐positive and Gram‐negative bacteria expressing this unique virulence‐associated nonulosonic acid. The synthesis of azido‐labeled Pse derivatives starting from d‐glucose and respective labeling studies are described.