The University of Southampton
University of Southampton Institutional Repository

Total synthesis of chrysophaentin F and approaches to related natural products

Total synthesis of chrysophaentin F and approaches to related natural products
Total synthesis of chrysophaentin F and approaches to related natural products
The chrysophaentins are a new family of natural products first isolated from the marine algae Chrysophaeum taylori in 2010.1,2 They have been found to have strong antibiotic activity, particularly against methicillin resistant Staphylococcus aureus (MRSA), multiple drug resistant SA (MDRSA) and vancomycin resistant Enterococcus faecium (VREF). Chrysophaentin A was identified as the most active member of the family with MIC50 values of 1.5 ± 0.7 and 1.3 ± 0.4 μg/mL against MRSA and MDRSA and 2.9 ± 0.8 μg/mL towards VREF, closely followed by chrysophaentins F and H.

This thesis describes the total synthesis of chrysophaentin F and progress towards the synthesis of chrysophaentins A and E. The synthetic strategy described herein is designed to give access to all chrysophaentins with minimal modification. It takes advantage of common building blocks and symmetry elements present throughout the chrysophaentin family and uses these to proceed via related intermediates. It uses a variety of transition metal catalysed C-C and C-O bond forming reactions to conjoin these building blocks, including Cu-catalysed Chan-Evans-Lam couplings, Pd- and Ni-catalysed sp-sp3 couplings and a Mo-catalysed RCAM. Furthermore, a late-stage hydrozirconation is used to install the (E)-vinyl chloride groups present in the natural products. This has resulted in the total synthesis of chrysophaentin F as a 2:1 mixture with a regioisomer and the preparation of a protected derivative of chrysophaentin E. Significant progress towards chrysophaentin A is also described.
University of Southampton
Matters, Rebecca Frances
ad2db74a-4952-40e5-942e-6c09e7c85c35
Matters, Rebecca Frances
ad2db74a-4952-40e5-942e-6c09e7c85c35
Harrowven, David C.
bddcfab6-dbde-49df-aec2-42abbcf5d10b

Matters, Rebecca Frances (2018) Total synthesis of chrysophaentin F and approaches to related natural products. University of Southampton, Doctoral Thesis, 237pp.

Record type: Thesis (Doctoral)

Abstract

The chrysophaentins are a new family of natural products first isolated from the marine algae Chrysophaeum taylori in 2010.1,2 They have been found to have strong antibiotic activity, particularly against methicillin resistant Staphylococcus aureus (MRSA), multiple drug resistant SA (MDRSA) and vancomycin resistant Enterococcus faecium (VREF). Chrysophaentin A was identified as the most active member of the family with MIC50 values of 1.5 ± 0.7 and 1.3 ± 0.4 μg/mL against MRSA and MDRSA and 2.9 ± 0.8 μg/mL towards VREF, closely followed by chrysophaentins F and H.

This thesis describes the total synthesis of chrysophaentin F and progress towards the synthesis of chrysophaentins A and E. The synthetic strategy described herein is designed to give access to all chrysophaentins with minimal modification. It takes advantage of common building blocks and symmetry elements present throughout the chrysophaentin family and uses these to proceed via related intermediates. It uses a variety of transition metal catalysed C-C and C-O bond forming reactions to conjoin these building blocks, including Cu-catalysed Chan-Evans-Lam couplings, Pd- and Ni-catalysed sp-sp3 couplings and a Mo-catalysed RCAM. Furthermore, a late-stage hydrozirconation is used to install the (E)-vinyl chloride groups present in the natural products. This has resulted in the total synthesis of chrysophaentin F as a 2:1 mixture with a regioisomer and the preparation of a protected derivative of chrysophaentin E. Significant progress towards chrysophaentin A is also described.

Text
RebeccaMattersThesis_TotalSynthesisofChrysophaentinF - Version of Record
Available under License University of Southampton Thesis Licence.
Download (9MB)

More information

Published date: May 2018

Identifiers

Local EPrints ID: 422234
URI: http://eprints.soton.ac.uk/id/eprint/422234
PURE UUID: ec148137-30cd-4123-bc5d-85cca69ee5ae
ORCID for David C. Harrowven: ORCID iD orcid.org/0000-0001-6730-3573

Catalogue record

Date deposited: 19 Jul 2018 16:30
Last modified: 28 Jun 2021 04:01

Export record

Contributors

Author: Rebecca Frances Matters
Thesis advisor: David C. Harrowven ORCID iD

University divisions

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.

×