Stereospecific dehydroxyfluorination and the synthesis of trifluoro D-hexose sugar analogues

Abstract

This thesis describes stereospecific fluorination reactions, and addresses the synthesis of fluorosugars. In Chapter 1, the influence of fluorine on the physical properties of organic molecules, as well as its stereoelectronic effects, are introduced. Furthermore, an overview of nucleophilic and electrophilic fluorination reactions is given. Chapter 2 describes the dehydroxyfluorination of allylic alcohol diastereoisomers 155a and 155b, which can proceed either by direct or allylic fluorination. The regio- and stereo- selectivities were also assessed. Chapter 3 outlines the synthesis of the novel trifluoro D-glucose analogue 193 and trifluoro D-altrose analogue 216. The transport of these hexose analogues across the red blood cell membranes was then explored, to investigate the influence of polarity versus hydrogen bonding ability in carbohydrate-protein interactions. Chapter 4 describes the development and optimisation of Bio’s methodology, to promote stereospecific dehydroxyfluorination of benzylic alcohols (R)-213 and (R)-227 by addition of TMS-amine additives 226 and 229. And finally Chapter 5 reports the experimental procedures as well as the characterisation and the crystallographic data of the molecules prepared in this thesis.