The University of Southampton
University of Southampton Institutional Repository

Synthesis of bioactive fluorinated bile acid analogues and investigating the influence of (deoxo)fluorination on alkanol and carbohydrate lipophilicity by a new logP determination method

Synthesis of bioactive fluorinated bile acid analogues and investigating the influence of (deoxo)fluorination on alkanol and carbohydrate lipophilicity by a new logP determination method
Synthesis of bioactive fluorinated bile acid analogues and investigating the influence of (deoxo)fluorination on alkanol and carbohydrate lipophilicity by a new logP determination method
Since the identification of bile acids as natural ligands for FXR and TGR5 receptors, huge interest has arisen in this field, including the synthesis of semi-synthetic bile acid derivatives to increase binding potency and selectivity. Fluorine introduction is an attractive strategy in drug design and property optimization. This thesis describes the synthesis of fluorinated analogues of bile acids and the lead compound 6-ECDCA. Interesting observations of effects of fluorination on crystal packing modes will also be discussed.

Another important application of fluorination is lipophilicity (logP) modulation. However, logP measurement of non-UV active compounds is rather cumbersome and hampers research toward the understanding how aliphatic fluorination influences lipophilicity. Over the course of this thesis, a novel and straightforward method was developed for accurate measurement of lipophilicity of fluorinated compounds by using 19F NMR. Unlike many other methods, there is no requirement of UV activity for quantification, or the need for calibration curves for logP estimation. Using this method, logP values for a large number of fluorinated compounds were determined. Interesting effects and trends from different fluorination patterns were observed, along with the impact of stereochemistry on lipophilicity.
University of Southampton
Wang, Zhong
ef9f8b13-c3f0-48d7-b8e2-95b0f757c30a
Wang, Zhong
ef9f8b13-c3f0-48d7-b8e2-95b0f757c30a
Linclau, Bruno
19b9cacd-b8e8-4c65-af36-6352cade84ba

Wang, Zhong (2016) Synthesis of bioactive fluorinated bile acid analogues and investigating the influence of (deoxo)fluorination on alkanol and carbohydrate lipophilicity by a new logP determination method. University of Southampton, Faculty of Natural and Environmental Sciences, Doctoral Thesis, 293pp.

Record type: Thesis (Doctoral)

Abstract

Since the identification of bile acids as natural ligands for FXR and TGR5 receptors, huge interest has arisen in this field, including the synthesis of semi-synthetic bile acid derivatives to increase binding potency and selectivity. Fluorine introduction is an attractive strategy in drug design and property optimization. This thesis describes the synthesis of fluorinated analogues of bile acids and the lead compound 6-ECDCA. Interesting observations of effects of fluorination on crystal packing modes will also be discussed.

Another important application of fluorination is lipophilicity (logP) modulation. However, logP measurement of non-UV active compounds is rather cumbersome and hampers research toward the understanding how aliphatic fluorination influences lipophilicity. Over the course of this thesis, a novel and straightforward method was developed for accurate measurement of lipophilicity of fluorinated compounds by using 19F NMR. Unlike many other methods, there is no requirement of UV activity for quantification, or the need for calibration curves for logP estimation. Using this method, logP values for a large number of fluorinated compounds were determined. Interesting effects and trends from different fluorination patterns were observed, along with the impact of stereochemistry on lipophilicity.

Text
Thesis Zhong Wang.pdf - Version of Record
Restricted to Repository staff only until 31 May 2022.
Available under License University of Southampton Thesis Licence.

More information

Published date: 31 January 2016
Organisations: University of Southampton, Chemistry

Identifiers

Local EPrints ID: 397966
URI: http://eprints.soton.ac.uk/id/eprint/397966
PURE UUID: 9ec5fd62-250b-448e-9231-6a4e8678a71b
ORCID for Bruno Linclau: ORCID iD orcid.org/0000-0001-8762-0170

Catalogue record

Date deposited: 15 Jul 2016 10:48
Last modified: 11 Jun 2019 00:36

Export record

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×