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Title: Studies towards the C1-C17 fragment of the potent antimitotic spongistatin 1
Author: Healy, M.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2002
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Abstract:
This thesis is divided into 7 chapters. Chapter 1 describes the history of the spongistatin family. The isolation of the spongistatins, cinachyrolide and the altohyrtins is reviewed. The structural assignments of these molecules is then discussed and their common identities highlighted. A discussion of the biological properties of the spongistatins then follows before summarising the structural features of the molecules and the issues they pose towards a total synthesis. The spiroketal fragments of the spongistatins are then examined more closely. Spiroketal containing natural products and synthetic methods towards spiroketals are then reviewed. Chapter 2 reviews the synthetic work which has been conducted towards the total synthesis of the spongistatins, paying attention to the 4 groups who have so far completed a total synthesis of one of the spongistatin molecules. Chapter 3 is a review of the strategy our group has taken towards the total synthesis of spongistatin 1. The synthesis of major fragments is described and synthetic problems that have been encountered and have led to a change in the strategy towards the AB spiroketal containing, C1-C17 fragment of spongistatin 1. Chapter 4 outlines the new strategy towards the C1-C17 fragment of spongistatin 1. Synthesis of the C8-C17 fragment is described in detail, with particular attention paid to functionalisation of the C13 alkene via a Wacker oxidation, Shapiro reaction and higher-order cuprate addition to a C12 epoxide. Coupling of a C8 aldehyde with an anomeric phosphonium salt is discussed, and the need for another change is strategy is outlined. Chapters 5 describes the new route to the AB spiroketal via a 1,3-diketone. Synthesis of this fragment is described, and modifications made due to protecting group issues are described in detail, culminating in the successful synthesis of the AB spiroketal. An exciting unified approach to the AB and CD spiroketals is then summarised in Chapter 6.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.603922  DOI: Not available
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