Towards the Synthesis of the Unusual Monosaccharides Found in the Shigella sonnei O-Antigen and Analysis of Shigella flexneri 2a Glycoconjugate Vaccine Samples
type: CreativeWork
description: Shigellosis (bacillary dysentery) is a severe inflammatory diarrhoeal disease in humans caused by the Gram-negative bacteria belonging to the Shigella species. Despite over 60 years of vaccine research, no licensed vaccine to prevent shigellosis is commercially available. Bioconjugate vaccines based on the O-antigen against various Shigella serotypes are under development. Shigella sonnei and Shigella flexneri 2a are the most prevalent serotypes in industrialised and developed countries respectively and is the subject of this study. This project involves the design and evaluation of alternative synthetic routes to derivatives of 2-acetamido-4-amino-2,4,6-trideoxy-β-D-galactopyranose (FucNAc4N/AAT) and 2-acetamido2-deoxy-α-L-altruronic acid (AltNAcA), the two unusual monosaccharides found in the repeating unit of the Shigella sonnei O-antigen. Since these sugars are not commercially available, synthetic derivatives are required as authentic standards for the analysis of the bioconjugate. Various routes to the FucNAc4N derivative were investigated and evaluated. Routes proceeding either through 1,6-anhydro-D-glucose or cyclohexyl-2-acetamido-1-thioglucoside were shown to have potential, but ultimately both were rejected on the basis of inefficient conversions in the early stages of the synthetic sequence. However, important insights were gained into the crucial challenge of differentiating O-3 and O-4, common to any approach involving starting materials with the D-gluco configuration. This led to preparation in good yield of phenyl 2-amino-2-N,3-Ocarbonyl-2-deoxy-1-thio-β-D-glucopyranoside as a key oxazolidinone-protected intermediate, which allowed for successful preparation of a FucNAc4N derivative in the form of a 4-azido-βthioglycoside. This was achieved in 10 steps from the commercially available 2-acetamido1,3,4,6-tetra-O-acetyl-β-D-glucopyranose in an overall yield of 17%. Synthesis of an AltNAcA derivative was initially investigated via a sequence starting fro…
abstract: Shigellosis (bacillary dysentery) is a severe inflammatory diarrhoeal disease in humans caused by the Gram-negative bacteria belonging to the Shigella species. Despite over 60 years of vaccine research, no licensed vaccine to prevent shigellosis is commercially available. Bioconjugate vaccines based on the O-antigen against various Shigella serotypes are under development. Shigella sonnei and Shigella flexneri 2a are the most prevalent serotypes in industrialised and developed countries respectively and is the subject of this study. This project involves the design and evaluation of alternative synthetic routes to derivatives of 2-acetamido-4-amino-2,4,6-trideoxy-β-D-galactopyranose (FucNAc4N/AAT) and 2-acetamido2-deoxy-α-L-altruronic acid (AltNAcA), the two unusual monosaccharides found in the repeating unit of the Shigella sonnei O-antigen. Since these sugars are not commercially available, synthetic derivatives are required as authentic standards for the analysis of the bioconjugate. Various routes to the FucNAc4N derivative were investigated and evaluated. Routes proceeding either through 1,6-anhydro-D-glucose or cyclohexyl-2-acetamido-1-thioglucoside were shown to have potential, but ultimately both were rejected on the basis of inefficient conversions in the early stages of the synthetic sequence. However, important insights were gained into the crucial challenge of differentiating O-3 and O-4, common to any approach involving starting materials with the D-gluco configuration. This led to preparation in good yield of phenyl 2-amino-2-N,3-Ocarbonyl-2-deoxy-1-thio-β-D-glucopyranoside as a key oxazolidinone-protected intermediate, which allowed for successful preparation of a FucNAc4N derivative in the form of a 4-azido-βthioglycoside. This was achieved in 10 steps from the commercially available 2-acetamido1,3,4,6-tetra-O-acetyl-β-D-glucopyranose in an overall yield of 17%. Synthesis of an AltNAcA derivative was initially investigated via a sequence starting fro…
author: Anderson, Taigh Byrne
keywords: Chemistry
date modified: 2026-07-22T22:22:38Z
provider: University of Cape Town
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Department of Chemistry

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property ID: Handle
value: http://hdl.handle.net/11427/33192