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Title: Studies towards the total synthesis of an anti-HIV natural product
Author: Guggiari, Sean
ISNI:       0000 0004 8507 1384
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 2019
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This thesis primarily concerns progress made towards the total synthesis of the natural product unciaphenol. The first half of Chapter 1 serves as an introduction to the target molecule and closely related enediyne natural products. This includes biological activity, proposed biosynthetic pathways, and previous synthetic efforts on the most closely related natural product to unciaphenol. The second half of Chapter 1 offers a brief historical perspective on the development of iminium ion and enamine organocatalysis. The use of such methods in the preparation of structural motifs similar to the core of unciaphenol is discussed. Chapter 2 details the proposed strategy for the total synthesis of unciaphenol, including an amine catalysed coupling of an isatin-derived α-keto ester with an α,β-unsaturated aldehyde. A general protocol for the preparation of such α-keto esters is presented in Chapter 3. The development of the proposed organocatalysed cyclisation is detailed in Chapter 4. This begins with optimisation of the reaction conditions and is followed by investigation of the substrate scope. A putative mechanism and elucidation of product stereochemistry is offered. Chapter 5 concerns the use of a model system to probe the proposed route to unciaphenol following the organocatalysed coupling. Finally, Chapter 6 presents progress made on the total synthesis of unciaphenol using fully functionalised substrates. Included are the preparation of α,β-unsaturated aldehydes for the organocatalysed cyclisation and transformations subsequent to this coupling. Full experimental details for all compounds prepared are offered further within the thesis.
Supervisor: Burton, Jonathan W. Sponsor: University of Oxford ; Engineering and Physical Sciences Research Council
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Chemistry, Organic