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The synthesis of A-ring fluorinated bile acid analogues

The synthesis of A-ring fluorinated bile acid analogues
The synthesis of A-ring fluorinated bile acid analogues
Bile acids are physiological detergent molecules with a function to absorb dietary lipids and hydrophobic molecules in the gastrointestinal tract. It has emerged that bile acids are also agonists for the FXR nuclear receptor and the TGR5 membrane-bound receptor, and are key in regulating metabolism via both genomic and non-genomic factors. It is also apparent that bile acids could play an important role in the treatment of Parkinson’s disease and some cancers. A number of pharmaceutical companies have developed selective BA receptor agonists, with some progressing through clinical trials for a variety of metabolic disorders.
Fluorine is used extensively in property optimisation due to its ability to modify a plethora of physicochemical effects. By selectively introducing fluorine into the bile acid skeleton, it is possible to modify hydrogen bonding properties, and thus improvements in receptor binding are conceivable. This thesis describes the synthesis of a number of fluorinated bile acid analogues, along with a discussion of some early biological results. Two interesting cases of an intramolecular C-F•••H-O hydrogen bond within the bile acid skeleton will also be presented
Watts, Joseph
09391492-1097-4cdd-bc4f-5b9f82421296
Watts, Joseph
09391492-1097-4cdd-bc4f-5b9f82421296
Linclau, Bruno
19b9cacd-b8e8-4c65-af36-6352cade84ba

Watts, Joseph (2016) The synthesis of A-ring fluorinated bile acid analogues. University of Southampton, Doctoral Thesis, 237pp.

Record type: Thesis (Doctoral)

Abstract

Bile acids are physiological detergent molecules with a function to absorb dietary lipids and hydrophobic molecules in the gastrointestinal tract. It has emerged that bile acids are also agonists for the FXR nuclear receptor and the TGR5 membrane-bound receptor, and are key in regulating metabolism via both genomic and non-genomic factors. It is also apparent that bile acids could play an important role in the treatment of Parkinson’s disease and some cancers. A number of pharmaceutical companies have developed selective BA receptor agonists, with some progressing through clinical trials for a variety of metabolic disorders.
Fluorine is used extensively in property optimisation due to its ability to modify a plethora of physicochemical effects. By selectively introducing fluorine into the bile acid skeleton, it is possible to modify hydrogen bonding properties, and thus improvements in receptor binding are conceivable. This thesis describes the synthesis of a number of fluorinated bile acid analogues, along with a discussion of some early biological results. Two interesting cases of an intramolecular C-F•••H-O hydrogen bond within the bile acid skeleton will also be presented

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Joe_Watts_07_02_207_thesis_final_copy_for_faculty_submission_1_ - Version of Record
Restricted to Repository staff only until 28 February 2023.
Available under License University of Southampton Thesis Licence.

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Published date: November 2016
Organisations: University of Southampton, Chemistry

Identifiers

Local EPrints ID: 410301
URI: http://eprints.soton.ac.uk/id/eprint/410301
PURE UUID: c4d05408-9df2-45eb-a6fe-55e5b3bb466a
ORCID for Bruno Linclau: ORCID iD orcid.org/0000-0001-8762-0170

Catalogue record

Date deposited: 07 Jun 2017 04:00
Last modified: 26 Feb 2020 01:26

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Contributors

Author: Joseph Watts
Thesis advisor: Bruno Linclau ORCID iD

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