Maleidride Natural Products
: Structural and Synthetic Studies

Student thesis: Doctoral ThesisDoctor of Philosophy (PhD)

Abstract

The maleidrides are a class of polyketide natural products which possess a broad range of herbicidal and fungicidal properties. An introduction to their bioactivity and biosynthesis is described in chapter one, before the isolation and structural determination of two members of this family, scytalidin and deoxyscytalidin is described in chapter two. The relative stereochemistry of both natural products was determined by X-ray crystallography, and the absolute stereochemistry proposed on the basis of biosynthetic studies.
In chapter three, the total synthesis of fulgenic diacids is described. The approach utilised a substitutionelimination reaction of nitroalkanes with an allylic bromide, in which two alkenes are formed concomitantly, including exclusive formation of an (E)-trisubstituted alkene moiety. This methodology is exemplified with the first total syntheses of the tricladic acids A-C, fungal natural products with interesting fungicidal and anti-cancer properties. This methodology underpinned the investigation of a biomimetic synthesis of deoxyscytalidin in chapter four. The desired cyclisation could not be achieved, however as a result of this investigation the structure of the natural product waquafranone B has been revised.
Finally, a de novo approach to the synthesis of scytalidin is described in chapter five. A strategy utilising two-carbon ring expansion of cyclic β-ketoesters was devised, with which the nine-membered carbocylic ring of scytalidin would be formed. The synthesis of late-stage intermediates is described.
Date of Award25 Jun 2019
Original languageEnglish
Awarding Institution
  • The University of Bristol
SupervisorRussell Cox (Supervisor) & Chris L Willis (Supervisor)

Keywords

  • Organic Synthesis
  • Natural Products
  • Total Synthesis
  • Biosynthesis

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