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Synthesis of fluorinated bile acids and investigation of their hydrogen bond properties

Synthesis of fluorinated bile acids and investigation of their hydrogen bond properties
Synthesis of fluorinated bile acids and investigation of their hydrogen bond properties
Bile acids are naturally occurring steroidal compounds present in the bile of mammals. They are involved in the absorption and digestion of ingested fats, lipophilic vitamins and drugs. In addition, they also control secretion and regulation of cholesterol metabolism.
Bile acids have recently emerged as signalling molecules of receptors such as FXR and TGR5. Ursodeoxycholic acid (UDCA) and its taurine conjugate TUDCA were shown to inhibit the expression of angiotensin converting enzyme 2, a membrane receptor which facilitates entry of different coronaviruses into the human body. In addition, TUDCA was also shown to have a neuroprotective function over mitochondria and endoplasmic reticulum, whose malfunctions are critical in the progression of neurodegenerative diseases such as Parkinson’s, Alzheimer’s and amyotrophic lateral sclerosis.
Fluorine is widely used in drug discovery to selectively modify physiochemical properties such as acidity and hydrogen bond donating capacity. Therefore, the introduction of fluorine to potential bile acid drug candidates is of interest. This thesis describes syntheses of several fluorinated bile acid derivatives with the aim to evaluate how strategic incorporation of fluorine influences the hydrogen bond donating capacity of vicinal hydroxy groups. Strategies that enable fluorination of non-standard bile acid positions, namely the D-ring, are also investigated herein.
Bile Acids and Salts/chemistry
University of Southampton
Kovacic, Kristina
341dad39-1119-43de-8d1d-6c071f88da65
Kovacic, Kristina
341dad39-1119-43de-8d1d-6c071f88da65
Linclau, Bruno
19b9cacd-b8e8-4c65-af36-6352cade84ba
Thompson, Sam
99b7e34e-fe24-401c-b7b0-64e56cbbbcb1

Kovacic, Kristina (2023) Synthesis of fluorinated bile acids and investigation of their hydrogen bond properties. University of Southampton, Doctoral Thesis, 319pp.

Record type: Thesis (Doctoral)

Abstract

Bile acids are naturally occurring steroidal compounds present in the bile of mammals. They are involved in the absorption and digestion of ingested fats, lipophilic vitamins and drugs. In addition, they also control secretion and regulation of cholesterol metabolism.
Bile acids have recently emerged as signalling molecules of receptors such as FXR and TGR5. Ursodeoxycholic acid (UDCA) and its taurine conjugate TUDCA were shown to inhibit the expression of angiotensin converting enzyme 2, a membrane receptor which facilitates entry of different coronaviruses into the human body. In addition, TUDCA was also shown to have a neuroprotective function over mitochondria and endoplasmic reticulum, whose malfunctions are critical in the progression of neurodegenerative diseases such as Parkinson’s, Alzheimer’s and amyotrophic lateral sclerosis.
Fluorine is widely used in drug discovery to selectively modify physiochemical properties such as acidity and hydrogen bond donating capacity. Therefore, the introduction of fluorine to potential bile acid drug candidates is of interest. This thesis describes syntheses of several fluorinated bile acid derivatives with the aim to evaluate how strategic incorporation of fluorine influences the hydrogen bond donating capacity of vicinal hydroxy groups. Strategies that enable fluorination of non-standard bile acid positions, namely the D-ring, are also investigated herein.

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Synthesis of fluorinated bile acids and investigation of their hydrogen bond properties - Version of Record
Restricted to Repository staff only until 30 June 2028.
Available under License University of Southampton Thesis Licence.
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Final-thesis-submission-Examination-Miss-Kristina-Kovacic
Restricted to Repository staff only
Available under License University of Southampton Thesis Licence.

More information

Published date: 19 May 2023
Keywords: Bile Acids and Salts/chemistry

Identifiers

Local EPrints ID: 477051
URI: http://eprints.soton.ac.uk/id/eprint/477051
PURE UUID: 11ab0e24-8944-4116-93e5-7a9311d01300
ORCID for Bruno Linclau: ORCID iD orcid.org/0000-0001-8762-0170
ORCID for Sam Thompson: ORCID iD orcid.org/0000-0001-6267-5693

Catalogue record

Date deposited: 24 May 2023 16:56
Last modified: 28 Sep 2023 01:46

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Contributors

Author: Kristina Kovacic
Thesis advisor: Bruno Linclau ORCID iD
Thesis advisor: Sam Thompson ORCID iD

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