{"id":{"repo_id":"cape-town","oai_identifier":"oai:open.uct.ac.za:11427/24464"},"canonical_url":"https://search.dev.ndltd.org/etd/cape-town/oai:open.uct.ac.za:11427/24464","repository":{"repo_id":"cape-town","name":"University of Cape Town","base_url":"https://open.uct.ac.za/oai/request"},"display":{"title":"Development of an alternative synthesis of 2-acetamido-2-deoxy-L-altruronic acid: an unusual sugar found in the O-specific polysaccharide of Shigella sonnei","abstract":"A new synthetic route has been explored for the preparation of derivatives of 2-acetamido-2-deoxy-L-altruronic acid (L-AltNAcA). This is a rare sugar found together with 2-acetamido-4-amino-2,4-dideoxy-D-fucose(D-FucNAc4N) in the repeating unit of Shigella sonnei. Derivatives are needed inter alia for chemical and spectroscopic calibration standards, and as building blocks for preparing oligomeric subunits of the O-polysaccharide antigen for possible incorporation into a synthetic glycoconjugate vaccine. Two synthetic routes were investigated. The first route successfully repeated a published four step sequence converting diacetone-D-glucose to 1,6-anhydro--L-idopyranose in a 38% yield overall, and a further selective benzylation at O-3. Attempts to discriminate between O-2, O-3 and O-4 using low temperature acylation or alkylation conditions were unsuccessful, but modest selectivity for the 4-benzoate was observed in a Bu₂SnO-mediated benzoylation, although this product could not be easily separated from other mono-benzoates. The second route started from N-acetyl-D-glucosamine which was successfully converted in the first step to 2-methyl-(1,2-dideoxyl-5,6-O-isopropylidene-α-D-glucofurano)-[2,1-d]-2-oxazoline. The oxazoline and dioxolane units could be selectively manipulated in a series of steps to afford 2-acetamido-2-deoxy-3-O-benzyl-6-O-t-butyldimethylsilyl-α-D-glucofuranosyl acetate in a 41% yield over four steps. This is a key synthetic intermediate in which the 5-OH is available for the required inversion step. During this study, an unusual minor side-product, 1,6-anhydro-2-acetamido-O-acetyl-2-deoxy-3-O-benzyl-α-D-glucofuranose, was isolated. While this was also a potentially useful intermediate, having only the 5-OH unprotected, it proved not possible to find conditions for optimizing this product. Inversion of configuration at C-5 in the 6-O-silylated glucofuranose was attempted via the 5-O-triflate and 5-O-mesylate: the triflate formed but was displaced in situ by the solvent pyridine to give an unusual 5-pyridinium derivative, while the mesylate was stable but unreactive towards subsequent SN2 inversion. These outcomes were attributed to the steric congestion imposed by the combination of the 3,4-cis-disubstitution of the furanose ring and the very bulky silyl substituent at O-6. While the goal of preparing L-AltNAcA was not achieved via these approaches, useful insights have been contributed towards the ongoing study.","abstract_html":"A new synthetic route has been explored for the preparation of derivatives of 2-acetamido-2-deoxy-L-altruronic acid (L-AltNAcA). This is a rare sugar found together with 2-acetamido-4-amino-2,4-dideoxy-D-fucose(D-FucNAc4N) in the repeating unit of Shigella sonnei. Derivatives are needed inter alia for chemical and spectroscopic calibration standards, and as building blocks for preparing oligomeric subunits of the O-polysaccharide antigen for possible incorporation into a synthetic glycoconjugate vaccine. Two synthetic routes were investigated. The first route successfully repeated a published four step sequence converting diacetone-D-glucose to 1,6-anhydro--L-idopyranose in a 38% yield overall, and a further selective benzylation at O-3. Attempts to discriminate between O-2, O-3 and O-4 using low temperature acylation or alkylation conditions were unsuccessful, but modest selectivity for the 4-benzoate was observed in a Bu₂SnO-mediated benzoylation, although this product could not be easily separated from other mono-benzoates. The second route started from N-acetyl-D-glucosamine which was successfully converted in the first step to 2-methyl-(1,2-dideoxyl-5,6-O-isopropylidene-α-D-glucofurano)-[2,1-d]-2-oxazoline. The oxazoline and dioxolane units could be selectively manipulated in a series of steps to afford 2-acetamido-2-deoxy-3-O-benzyl-6-O-t-butyldimethylsilyl-α-D-glucofuranosyl acetate in a 41% yield over four steps. This is a key synthetic intermediate in which the 5-OH is available for the required inversion step. During this study, an unusual minor side-product, 1,6-anhydro-2-acetamido-O-acetyl-2-deoxy-3-O-benzyl-α-D-glucofuranose, was isolated. While this was also a potentially useful intermediate, having only the 5-OH unprotected, it proved not possible to find conditions for optimizing this product. Inversion of configuration at C-5 in the 6-O-silylated glucofuranose was attempted via the 5-O-triflate and 5-O-mesylate: the triflate formed but was displaced in situ by the solvent pyridine to give an unusual 5-pyridinium derivative, while the mesylate was stable but unreactive towards subsequent SN2 inversion. These outcomes were attributed to the steric congestion imposed by the combination of the 3,4-cis-disubstitution of the furanose ring and the very bulky silyl substituent at O-6. While the goal of preparing L-AltNAcA was not achieved via these approaches, useful insights have been contributed towards the ongoing study.","abstract_has_math":false,"creators":["Anderson, Kirstin P C"],"institution":"Department of Chemistry","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":["Gammon, David W","Ravenscroft, Neil"],"committee_chairs":[],"committee_members":[],"year":2017,"date_issued":"2017","date_published":"2017","updated_at":"2026-07-24T01:33:36Z","subjects":[],"languages":["eng"],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/11427/24464","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Gammon, David W","Ravenscroft, Neil"]},{"key":"dc:creator","label":"Author","values":["Anderson, Kirstin P C"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2017-06-01T10:14:08Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2017-06-01T10:14:08Z"]},{"key":"dc:date.issued","label":"Date","values":["2017"]},{"key":"dc:publisher.department","label":"Dc Publisher Department","values":["Department of Chemistry"]},{"key":"dc:publisher.institution","label":"Dc Publisher Institution","values":["University of Cape Town"]},{"key":"dc:type","label":"Dc Type","values":["Master Thesis"]},{"key":"dc:type.qualificationlevel","label":"Dc Type Qualificationlevel","values":["Masters"]},{"key":"dc:type.qualificationname","label":"Dc Type Qualificationname","values":["MSc"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language.iso","label":"Language (ISO)","values":["eng"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["http://hdl.handle.net/11427/24464"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["A new synthetic route has been explored for the preparation of derivatives of 2-acetamido-2-deoxy-L-altruronic acid (L-AltNAcA). This is a rare sugar found together with 2-acetamido-4-amino-2,4-dideoxy-D-fucose(D-FucNAc4N) in the repeating unit of Shigella sonnei. Derivatives are needed inter alia for chemical and spectroscopic calibration standards, and as building blocks for preparing oligomeric subunits of the O-polysaccharide antigen for possible incorporation into a synthetic glycoconjugate vaccine. Two synthetic routes were investigated. The first route successfully repeated a published four step sequence converting diacetone-D-glucose to 1,6-anhydro--L-idopyranose in a 38% yield overall, and a further selective benzylation at O-3. Attempts to discriminate between O-2, O-3 and O-4 using low temperature acylation or alkylation conditions were unsuccessful, but modest selectivity for the 4-benzoate was observed in a Bu₂SnO-mediated benzoylation, although this product could not be easily separated from other mono-benzoates. The second route started from N-acetyl-D-glucosamine which was successfully converted in the first step to 2-methyl-(1,2-dideoxyl-5,6-O-isopropylidene-α-D-glucofurano)-[2,1-d]-2-oxazoline. The oxazoline and dioxolane units could be selectively manipulated in a series of steps to afford 2-acetamido-2-deoxy-3-O-benzyl-6-O-t-butyldimethylsilyl-α-D-glucofuranosyl acetate in a 41% yield over four steps. This is a key synthetic intermediate in which the 5-OH is available for the required inversion step. During this study, an unusual minor side-product, 1,6-anhydro-2-acetamido-O-acetyl-2-deoxy-3-O-benzyl-α-D-glucofuranose, was isolated. While this was also a potentially useful intermediate, having only the 5-OH unprotected, it proved not possible to find conditions for optimizing this product. Inversion of configuration at C-5 in the 6-O-silylated glucofuranose was attempted via the 5-O-triflate and 5-O-mesylate: the triflate formed but was displaced in situ by the solvent pyridine to give an unusual 5-pyridinium derivative, while the mesylate was stable but unreactive towards subsequent SN2 inversion. These outcomes were attributed to the steric congestion imposed by the combination of the 3,4-cis-disubstitution of the furanose ring and the very bulky silyl substituent at O-6. While the goal of preparing L-AltNAcA was not achieved via these approaches, useful insights have been contributed towards the ongoing study."]},{"key":"dc:title","label":"Title","values":["Development of an alternative synthesis of 2-acetamido-2-deoxy-L-altruronic acid: an unusual sugar found in the O-specific polysaccharide of Shigella sonnei"]}]}],"canonical_facts":{"dc:contributor.advisor":["Gammon, David W","Ravenscroft, Neil"],"dc:creator":["Anderson, Kirstin P C"],"dc:date.accessioned":["2017-06-01T10:14:08Z"],"dc:date.available":["2017-06-01T10:14:08Z"],"dc:date.issued":["2017"],"dc:description.abstract":["A new synthetic route has been explored for the preparation of derivatives of 2-acetamido-2-deoxy-L-altruronic acid (L-AltNAcA). This is a rare sugar found together with 2-acetamido-4-amino-2,4-dideoxy-D-fucose(D-FucNAc4N) in the repeating unit of Shigella sonnei. Derivatives are needed inter alia for chemical and spectroscopic calibration standards, and as building blocks for preparing oligomeric subunits of the O-polysaccharide antigen for possible incorporation into a synthetic glycoconjugate vaccine. Two synthetic routes were investigated. The first route successfully repeated a published four step sequence converting diacetone-D-glucose to 1,6-anhydro--L-idopyranose in a 38% yield overall, and a further selective benzylation at O-3. Attempts to discriminate between O-2, O-3 and O-4 using low temperature acylation or alkylation conditions were unsuccessful, but modest selectivity for the 4-benzoate was observed in a Bu₂SnO-mediated benzoylation, although this product could not be easily separated from other mono-benzoates. The second route started from N-acetyl-D-glucosamine which was successfully converted in the first step to 2-methyl-(1,2-dideoxyl-5,6-O-isopropylidene-α-D-glucofurano)-[2,1-d]-2-oxazoline. The oxazoline and dioxolane units could be selectively manipulated in a series of steps to afford 2-acetamido-2-deoxy-3-O-benzyl-6-O-t-butyldimethylsilyl-α-D-glucofuranosyl acetate in a 41% yield over four steps. This is a key synthetic intermediate in which the 5-OH is available for the required inversion step. During this study, an unusual minor side-product, 1,6-anhydro-2-acetamido-O-acetyl-2-deoxy-3-O-benzyl-α-D-glucofuranose, was isolated. While this was also a potentially useful intermediate, having only the 5-OH unprotected, it proved not possible to find conditions for optimizing this product. Inversion of configuration at C-5 in the 6-O-silylated glucofuranose was attempted via the 5-O-triflate and 5-O-mesylate: the triflate formed but was displaced in situ by the solvent pyridine to give an unusual 5-pyridinium derivative, while the mesylate was stable but unreactive towards subsequent SN2 inversion. These outcomes were attributed to the steric congestion imposed by the combination of the 3,4-cis-disubstitution of the furanose ring and the very bulky silyl substituent at O-6. While the goal of preparing L-AltNAcA was not achieved via these approaches, useful insights have been contributed towards the ongoing study."],"dc:identifier.uri":["http://hdl.handle.net/11427/24464"],"dc:language.iso":["eng"],"dc:publisher.department":["Department of Chemistry"],"dc:publisher.institution":["University of Cape Town"],"dc:title":["Development of an alternative synthesis of 2-acetamido-2-deoxy-L-altruronic acid: an unusual sugar found in the O-specific polysaccharide of Shigella sonnei"],"dc:type":["Master Thesis"],"dc:type.qualificationlevel":["Masters"],"dc:type.qualificationname":["MSc"]},"updated_at":"2026-07-24T01:33:36Z"}