Towards the Synthesis of Pseudaminic Acid & Related Analogues as Substrates for Chemoenzymatic Studies

Session: 
S5.2 Bacterial glycan assembly
Code: 
FL5.2.2
Location (hall): 
Mannose
Start/end time: 
Tuesday, July 2, 2019 - 15:20 to 15:25
Abdullah
Hassan

Abdullah A. Hassan1

1University College Dublin (UCD), Dublin, Ireland

Bacterial infections are one of the leading threats to both human health and food productions world-wide. The role of sialic acids in microbial pathogenesis has not been fully understood yet. Structural complexity and inability to gain access to pure material has impeded this effort. Sialic acids are a group of unusual sugars that consist of a 9-carbon backbone typically found at the non-reducing (terminal) end of oligosaccharide chains on glycoproteins and glycolipids. Proteins that bind sialic acids are responsible for a broad range of biological processes, including intercellular adhesion, signalling and microbial attachment.

Thus, in order to study substrate specificity of sialic acid enzymes unique to pathogenic bacteria, chemical preparation of their respective substrates and analogues were explored. Herein described is the chemical syntheses of novel precursors of pseudaminic acid and 6-O-functionalised N-acetyl-D-mannosamine derivatives from commercially available N-acetyl-D-glucosamine and N-acetyl-D-mannosamine respectively. Synthesis of an advanced intermediate towards pseudaminic acid, L-idosamine, was achieved via a Rh-catalysed hydrogenation of an exocyclic olefin, which itself was produced by elimination of an alkyl halide moiety. Subsequent oxidation of the secondary alcohol of L-idosamine gave rise to its corresponding ketone which was utilised to install the desired amine functionality by reductive amination of an oxime derivative. A convenient chemoenzymatic strategy for the synthesis of neuraminic acid analogues derivatised at C-9 is also described. Furthermore, a mini-library of novel sialic acid fluorophores at the anomeric position are presented.

Figure 1: Selected Sialic Acid Structures 

References: 
  1. Varki, A. Nature, 2007, 446, 1023–1029.
  2. Gurung, M.; Raeder, I.; Altermark, B.; Smalas, A. Glycobiology, 2013, 23, 806-819.
  3. Lee, Y.; Kubota, A.; Ishiwata, A.; Ito, Y. Tetrahedron Letters, 2011, 52, 418-421.
  4. Berg, T.; Gurung, M.; Altermark, B.; Smalås, A.; Ræder, I. Carbohydrate Research, 2015, 402, 133.
  5. C. Navuluri and D. Crich, Angew. Chem., Int. Ed., 2013, 52, 11339–11342.

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