Thesis-2000-Davies.pdf (3.58 MB)
Approaches towards the synthesis of the natural product phorbol
thesis
posted on 2018-10-26, 10:29 authored by Darren DaviesThis thesis has been divided into three sections. The biological activity and the synthetic
approaches towards the total synthesis of phorbol have been reviewed in chapter one, our
own research discussed in chapter two and experimental details outlined in chapter three.
Chapter one comprises a review of the structure, isolation and biological activity of some
naturally occurring phorbol esters and their biosynthesis. The role of protein kinase C in
the wide variety of biological responses demonstrated by the phorbol esters has also been
discussed. Coverage of the part played by phorbol esters in the elucidation of
carcinogenesis has also been included.
The various synthetic routes to the AB, ABC and ABD ring systems and the total synthesis
of phorbol have also been discussed. A brief overview of our own IMDA approach to
provide the tigliane framework has been included in this section. The review highlights the
wide range of synthetic strategies which have been employed and includes the routes to
date which provide the tigliane ring system enantiomerically pure.
Our own research which involves an IMDA reaction as the key step towards the total
synthesis of phorbol is presented in the second chapter. Two alternative routes towards the
preparation of the oxygenated IMDA precursor have been discussed.
The convergent strategy described herein achieves the rapid construction of the tigliane ring
system as well as highly functionalised subunits and Diels-Alder adducts and demonstrates
the potential for application towards the total synthesis of phorbol and related compounds.
Funding
SmithKline Beecham plc.
History
School
- Science
Department
- Chemistry
Publisher
© Darren DaviesPublisher statement
This work is made available according to the conditions of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) licence. Full details of this licence are available at: https://creativecommons.org/licenses/by-nc-nd/4.0/Publication date
2000Notes
A Doctoral Thesis. Submitted in partial fulfilment of the requirements for the award of Doctor of Philosophy at Loughborough University.Language
- en