Full Text Available
Note: Clicking the button above will open the full text document at the original institutional repository in a new window.
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
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 f...
Saved in:
| Main Author: | |
|---|---|
| Other Authors: | |
| Format: | Thesis |
| Language: | English |
| Published: |
Department of Chemistry
2017
|
| Subjects: | |
| Tags: |
No Tags, Be the first to tag this record!
|
| _version_ | 1867613140246593536 |
|---|---|
| access_status_str | Open Access |
| author | Anderson, Kirstin P C |
| author2 | Gammon, David W |
| author_browse | Anderson, Kirstin P C Gammon, David W |
| author_facet | Gammon, David W Anderson, Kirstin P C |
| author_sort | Anderson, Kirstin P C |
| collection | Thesis |
| description | 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. |
| format | Thesis |
| id | oai:open.uct.ac.za:11427/24464 |
| institution | University of Cape Town (South Africa) |
| language | eng |
| last_indexed | 2026-06-10T12:31:24.573Z |
| license_str | Not specified — see source repository |
| provenance_str_mv | Harvested via OAI-PMH from UCTD — University of Cape Town Open Access Repository |
| publishDate | 2017 |
| publishDateRange | 2017 |
| publishDateSort | 2017 |
| publisher | Department of Chemistry |
| publisherStr | Department of Chemistry |
| record_format | dspace |
| source_str | UCTD — University of Cape Town Open Access Repository |
| spelling | oai:open.uct.ac.za:11427/24464 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 Anderson, Kirstin P C Gammon, David W Ravenscroft, Neil Chemistry 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. 2017-06-01T10:14:08Z 2017-06-01T10:14:08Z 2017 Master Thesis Masters MSc http://hdl.handle.net/11427/24464 eng application/pdf Department of Chemistry Faculty of Science University of Cape Town |
| spellingShingle | Chemistry Anderson, Kirstin P C 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 |
| thesis_degree_str | Master's |
| 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | Chemistry |
| url | http://hdl.handle.net/11427/24464 |
| work_keys_str_mv | AT andersonkirstinpc developmentofanalternativesynthesisof2acetamido2deoxylaltruronicacidanunusualsugarfoundintheospecificpolysaccharideofshigellasonnei |