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Synthesis of gemcitabine and it's tetrafluorinated analogues

Synthesis of gemcitabine and it's tetrafluorinated analogues
Synthesis of gemcitabine and it's tetrafluorinated analogues
A novel synthesis of the 2-deoxy-2,2-difluorocytidine nucleoside analogue gemcitabine has been achieved. Starting from the known 3,5-O-dibenzoyl-2- deoxy-2,2-difluororibose, the nucleobase moiety is constructed in a linear fashion, using amino- or urea glycosylation methodology. This methodology has also been employed to synthesise nucleosides containing a tetrafluorinated ribose sugar and has been compared to conventional convergent nucleobase introduction methods. In this respect, a high-yielding Mitsunobu-based protocol has also been developed. Both purine and pyrimidine analogues have been synthesised. The aminoglycosylation methodology has been investigated with a range of amines. The methodology proves high-yielding for primary amines and lesshindered secondary amines. In contrast to expectations, their stability in acidic media was not very high. Anomerisation and ring isomerisation studies have been conducted
Brown, Kylie J.
4fa05c54-c25b-46c8-a521-2d5f9514aae7
Brown, Kylie J.
4fa05c54-c25b-46c8-a521-2d5f9514aae7
Linclau, Bruno
19b9cacd-b8e8-4c65-af36-6352cade84ba

Brown, Kylie J. (2011) Synthesis of gemcitabine and it's tetrafluorinated analogues. University of Southampton, Chemistry, Doctoral Thesis, 244pp.

Record type: Thesis (Doctoral)

Abstract

A novel synthesis of the 2-deoxy-2,2-difluorocytidine nucleoside analogue gemcitabine has been achieved. Starting from the known 3,5-O-dibenzoyl-2- deoxy-2,2-difluororibose, the nucleobase moiety is constructed in a linear fashion, using amino- or urea glycosylation methodology. This methodology has also been employed to synthesise nucleosides containing a tetrafluorinated ribose sugar and has been compared to conventional convergent nucleobase introduction methods. In this respect, a high-yielding Mitsunobu-based protocol has also been developed. Both purine and pyrimidine analogues have been synthesised. The aminoglycosylation methodology has been investigated with a range of amines. The methodology proves high-yielding for primary amines and lesshindered secondary amines. In contrast to expectations, their stability in acidic media was not very high. Anomerisation and ring isomerisation studies have been conducted

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More information

Published date: 26 April 2011
Organisations: University of Southampton

Identifiers

Local EPrints ID: 193063
URI: https://eprints.soton.ac.uk/id/eprint/193063
PURE UUID: c6cdd563-ba76-4f8b-b5ae-df8aee0b29a2
ORCID for Bruno Linclau: ORCID iD orcid.org/0000-0001-8762-0170

Catalogue record

Date deposited: 12 Jul 2011 10:02
Last modified: 06 Jun 2018 12:52

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Contributors

Author: Kylie J. Brown
Thesis advisor: Bruno Linclau ORCID iD

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