Total Syntheses of Conjugation-Ready Repeating Units of Acinetobacter baumannii AB5075 for Glycoconjugate Vaccine Development.
Shuo ZhangPeter H SeebergerPublished in: Chemistry (Weinheim an der Bergstrasse, Germany) (2021)
Acinetobacter baumannii is an opportunistic pathogen that causes serious nosocomial infections. One of the multidrug-resistant strains, AB5075, can result in bacteremia, pneumonia and wound infections associated with high morbidity and mortality. The structurally unique glycans on the surface of these bacteria are attractive targets for the development of glycoconjugate vaccines. Here, we report the first total synthesis of the densely functionalized trisaccharide repeating unit of A. baumannii AB5075 as well as two analogues. The construction of 1,2-cis linkages between the rare sugars relies on a double-serial inversion strategy. The judicious selection of building blocks and reaction conditions allowed for stereoselective glycosylations, the installation of acetamido groups and the (S)-3-hydroxybutanoyl chain.
Keyphrases
- acinetobacter baumannii
- multidrug resistant
- drug resistant
- gram negative
- pseudomonas aeruginosa
- klebsiella pneumoniae
- escherichia coli
- magnetic resonance imaging
- high resolution
- candida albicans
- contrast enhanced
- acute respiratory distress syndrome
- electron transfer
- respiratory failure
- structure activity relationship