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The synthesis of polyfluorinated carbohydrates

The synthesis of polyfluorinated carbohydrates
The synthesis of polyfluorinated carbohydrates
Carbohydrates are essential to many fundamental biological processes throughout Nature. Although generally specific for their cognate protein receptors, typical protein-carbohydrate affinities are only in the micromolar to millimolar range. Polyfluorination has emerged as an attractive strategy to enhance this affinity in order to develop carbohydrate-based inhibitors and therapeutics. This thesis describes three syntheses of 3,4-dideoxy-3,3,4,4-tetrafluoro-Dmannopyranose and D-glucopyranose.

Polyfluorination of carbohydrates has important consequences on the hydrogen bond properties of the adjacent alcohols and particularly, difluorination in the β-position of an alcohol group is expected to significantly reduce its hydrogen bond acceptor capacity. For these cases, the substitution of the alcohol group for the intrinsically more nucleophilic amino group is proposed in order to restore this hydrogen bond accepting capacity. Hence, the synthesis of 2-amino-2,3,4-trideoxy-3,3,4,4-tetrafluoro-D-mannopyranose, D-glucopyranose, 4-amino-2,3,4-trideoxy-2,2,3,3-tetrafluoro-D-galactopyranose and D-glucopyranose as well as 3-amino-2,3-dideoxy-2,2-difluoro-D-galactopyranose is reported in this thesis.

In the course of this work, a novel diastereoselective Honda-Reformatsky addition reaction of ethyl bromodifluoroacetate to various α-chiral α-oxygenated N-tert-butanesulfinylimines is described to access to α,α-difluoro-β-amino acids and 2,2-difluoro-3-amino carbohydrate analogues. In addition, an extension of the Konno procedure to introduce a tetrafluoroalkylidene moiety was developed.
University of Southampton
Fontenelle, Clement
c746c5ea-96bc-46c2-849d-47215ab58c03
Fontenelle, Clement
c746c5ea-96bc-46c2-849d-47215ab58c03
Linclau, Bruno
19b9cacd-b8e8-4c65-af36-6352cade84ba

Fontenelle, Clement (2014) The synthesis of polyfluorinated carbohydrates. University of Southampton, Chemistry, Doctoral Thesis, 313pp.

Record type: Thesis (Doctoral)

Abstract

Carbohydrates are essential to many fundamental biological processes throughout Nature. Although generally specific for their cognate protein receptors, typical protein-carbohydrate affinities are only in the micromolar to millimolar range. Polyfluorination has emerged as an attractive strategy to enhance this affinity in order to develop carbohydrate-based inhibitors and therapeutics. This thesis describes three syntheses of 3,4-dideoxy-3,3,4,4-tetrafluoro-Dmannopyranose and D-glucopyranose.

Polyfluorination of carbohydrates has important consequences on the hydrogen bond properties of the adjacent alcohols and particularly, difluorination in the β-position of an alcohol group is expected to significantly reduce its hydrogen bond acceptor capacity. For these cases, the substitution of the alcohol group for the intrinsically more nucleophilic amino group is proposed in order to restore this hydrogen bond accepting capacity. Hence, the synthesis of 2-amino-2,3,4-trideoxy-3,3,4,4-tetrafluoro-D-mannopyranose, D-glucopyranose, 4-amino-2,3,4-trideoxy-2,2,3,3-tetrafluoro-D-galactopyranose and D-glucopyranose as well as 3-amino-2,3-dideoxy-2,2-difluoro-D-galactopyranose is reported in this thesis.

In the course of this work, a novel diastereoselective Honda-Reformatsky addition reaction of ethyl bromodifluoroacetate to various α-chiral α-oxygenated N-tert-butanesulfinylimines is described to access to α,α-difluoro-β-amino acids and 2,2-difluoro-3-amino carbohydrate analogues. In addition, an extension of the Konno procedure to introduce a tetrafluoroalkylidene moiety was developed.

Text
Final thesis C Fontenelle - Version of Record
Restricted to Repository staff only until 31 January 2021.
Available under License University of Southampton Thesis Licence.

More information

Published date: December 2014
Organisations: University of Southampton, Chemistry

Identifiers

Local EPrints ID: 374676
URI: http://eprints.soton.ac.uk/id/eprint/374676
PURE UUID: f4fa91fc-2ad6-46ec-8d5b-23629c01b503
ORCID for Clement Fontenelle: ORCID iD orcid.org/0000-0002-1630-3407
ORCID for Bruno Linclau: ORCID iD orcid.org/0000-0001-8762-0170

Catalogue record

Date deposited: 03 Mar 2015 09:52
Last modified: 24 May 2019 00:37

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Contributors

Author: Clement Fontenelle ORCID iD
Thesis advisor: Bruno Linclau ORCID iD

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