Abstract
Polyketides are a large family of structurally diverse natural products derived from the secondary metabolism of living organisms such as bacteria and fungi. Polyketide natural products and their derivatives continue to be important leads for the discovery of biologically active compounds and an inspiration for novel strategies in organic synthesis.Chapter one describes the investigations into the spirotetronate formation of polyketides abyssomicin C and abyssomicin 2. The modular synthesis of linear precursors 28 and 37 is discussed, and the substrates were used in in vitro assays to probe the selectivity of Diels-Alderases AbyU and AbmU, from their respective biosynthetic pathways. The substrate scope and selectivity of AbyU was also investigated herein, along with in vitro assays with genetically engineered mutants of AbyU.
Chapter two describes the investigations into the antifungal maleidride viburspiran 158. The synthetic investigations towards the racemic carbocyclic core 202b are described, which includes a key [2+2]-photocatalysed de Mayo reaction step to introduce the bridged C-5 and C-8 quaternary centres. Late-stage functionalisation strategies including investigations into pentyl chain introduction, isomerisation of exo-alkene 202a to an internal endo-alkene and a proposed total synthesis of (±)-viburspiran 158 are described.
| Date of Award | 24 Jan 2023 |
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| Original language | English |
| Awarding Institution |
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| Supervisor | Chris L Willis (Supervisor) & Matthew P Crump (Supervisor) |