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Title: Design and synthesis of potential inhibitors of fucosyltransferases
Author: Rae, Christine Mary
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1997
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This thesis describes the design and synthetic approach to a potential transition state inhibitor 26 of an α(1.3)-fucosyltransferase - an important enzyme involved in the inflammatory response where white blood cells are recruited to the site of injury. Fig. 1227A. Chapter 1 reviews the literature of potential inhibitors of both glycosyltransferases and glycosidases and outlines the aim of the project. Chapter 2 reveals the retrosynthetic strategy adopted for the trisubstrate analogue 26 and of the core azasugar portion which is a bis-hydroxymethyl piperidine 27. The synthetic challenge in this project resided in the synthesis of this unit and initially, an asymmetric synthesis of the known azasugar L-deoxyfuconojirimycin (DFJ) 7 which contains four of the required stereogenic centres of the core azasugar 27 was investigated. Chapter 3 describes the successful synthesis of 7 in 14 steps commencing from the readily available amino acid N-Box-L-alanine 51. Fig. 1227B. It was envisaged that the route to DFJ could subsequently be elaborated to the bis-dihydroxymethyl piperidine 27, but due to unforeseen problems a revised approach to the prime target from N-Box-L-alanine 51 was adopted. Chapter 4 outlines 10 steps that have been completed en route to an appropriately functionalised acyclic system which is anticipated to undergo a Lewis acid catalysed 6-exo-tet cyclisation of an amine function onto a gem-disubstituted epoxide to furnish a cyclised precursor to the target azasugar 27.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available