The University of Southampton
University of Southampton Institutional Repository

Towards the total synthesis of vibralactone and the miuraenamides

Towards the total synthesis of vibralactone and the miuraenamides
Towards the total synthesis of vibralactone and the miuraenamides
This thesis describes the efforts made towards the total synthesis of vibralactone and the miuraenamides. Initially, the attempted synthesis and derivatisation of vibralactone, a pancreatic lipase inhibiting fused bicyclic ?-lactone, will be discussed.

Vibralactone provides an interesting synthetic challenge not only because of its potent biological activity, but also due to its unique structure when compared to biologically related natural products. Herein, several ring closing metathesis (RCM) and aldol condensation strategies towards vibralactone’s cyclopentene ring are presented.

Following diastereoselective addition reactions, metathesis approaches have successfully provided two racemic ibralactone derivatives. A novel auxiliary was subsequently implemented towards a stereoselective formal synthesis of a vibralactone model compound. An alternative aldol condensation approach was then investigated to optimise the synthesis of vibralactone intermediates.

The synthetic approach towards the miuraenamide family is then described. The miuraenamides are macrocyclic depsipeptides which have been shown to possess potent anti-fungal activity. Miuraenamide A has also been shown to stabilise actin filaments. This biological activity makes the miuraenamide family interesting synthetic targets towards the development of novel anti-fungal and anti-cancer therapeutics.

The synthesis towards miuraenamide A, via miuraenamide E, is described. The synthesis of the miuraenamide hydrocarbon fragment using stereoselective catalytic procedures was successfully achieved. The remaining peptide fragment was then synthesised using developed amino acid functionalisation and coupling techniques.

Finally, optimisation of the union of each of the fragments was investigated, consequently leading to the successful synthesis of a linear, protected, miuraenamide E derivative.
Heap, Robert
c1557a74-f91f-4a3d-8767-23abe717065c
Heap, Robert
c1557a74-f91f-4a3d-8767-23abe717065c
Brown, Richard C.D.
21ce697a-7c3a-480e-919f-429a3d8550f5

Heap, Robert (2014) Towards the total synthesis of vibralactone and the miuraenamides. University of Southampton, Chemistry, Doctoral Thesis, 258pp.

Record type: Thesis (Doctoral)

Abstract

This thesis describes the efforts made towards the total synthesis of vibralactone and the miuraenamides. Initially, the attempted synthesis and derivatisation of vibralactone, a pancreatic lipase inhibiting fused bicyclic ?-lactone, will be discussed.

Vibralactone provides an interesting synthetic challenge not only because of its potent biological activity, but also due to its unique structure when compared to biologically related natural products. Herein, several ring closing metathesis (RCM) and aldol condensation strategies towards vibralactone’s cyclopentene ring are presented.

Following diastereoselective addition reactions, metathesis approaches have successfully provided two racemic ibralactone derivatives. A novel auxiliary was subsequently implemented towards a stereoselective formal synthesis of a vibralactone model compound. An alternative aldol condensation approach was then investigated to optimise the synthesis of vibralactone intermediates.

The synthetic approach towards the miuraenamide family is then described. The miuraenamides are macrocyclic depsipeptides which have been shown to possess potent anti-fungal activity. Miuraenamide A has also been shown to stabilise actin filaments. This biological activity makes the miuraenamide family interesting synthetic targets towards the development of novel anti-fungal and anti-cancer therapeutics.

The synthesis towards miuraenamide A, via miuraenamide E, is described. The synthesis of the miuraenamide hydrocarbon fragment using stereoselective catalytic procedures was successfully achieved. The remaining peptide fragment was then synthesised using developed amino acid functionalisation and coupling techniques.

Finally, optimisation of the union of each of the fragments was investigated, consequently leading to the successful synthesis of a linear, protected, miuraenamide E derivative.

Text
Robert Heap corrected PhD thesis.pdf - Other
Download (6MB)

More information

Published date: 17 November 2014
Organisations: University of Southampton, Chemistry

Identifiers

Local EPrints ID: 374535
URI: http://eprints.soton.ac.uk/id/eprint/374535
PURE UUID: 305ff974-7dcf-44a0-82ba-c63eeae4504a
ORCID for Richard C.D. Brown: ORCID iD orcid.org/0000-0003-0156-7087

Catalogue record

Date deposited: 23 Feb 2015 10:48
Last modified: 15 Mar 2024 05:13

Export record

Contributors

Author: Robert Heap
Thesis advisor: Richard C.D. Brown ORCID iD

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.

×