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Thesis-2000-Davies.pdf (3.58 MB)

Approaches towards the synthesis of the natural product phorbol

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posted on 2018-10-26, 10:29 authored by Darren Davies
This 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 Davies

Publisher 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

2000

Notes

A Doctoral Thesis. Submitted in partial fulfilment of the requirements for the award of Doctor of Philosophy at Loughborough University.

Language

  • en

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