The anomerisation of glycosidic linkages

Abstract

This thesis deals with the anomerisation of glycosidic linkages using TiCl4 and SnCl4. Methods involving the Lewis acid induced anomerisations of glycosides have been published over the past decade, however this methodology has not been widely utilised in carbohydrate chemistry due to low yields, large variations in selectivity, and the need for specific functional groups (e.g., carbamate). It is felt that a better understanding of the anomerisation reaction could be achieved by probing the effects of protecting groups and pushing the reaction to it limits. Chapter 1 deals with the anomerisation of glycosyl azides. Previous work by Murphy et al. has led to reasonable but not high selectivity using SnCl4. Since this work was carried out a seminal publication by Murphy et al. demonstrated the advantages of using TiCl4 in anomerisation reactions. The application of TiCl4 and varying the carboxylic functionality from acid to ester gave the desired high selectivities in good yields. Chapter 2 applies this successful approach to the anomerisation of disaccharide substrates, resulting in regioselective anomerisations and giving the desired alpha-products in high selectivities and yields. Chapter 3 deals with the influence of protecting groups on the rate of the anomerisation reaction. The rate of anomerisation for has been quantified for 34 substrates in an attempt to elucidate the influence of the steric and electronic effects. It was evident from the results obtained that both steric and electronic effects have an influence on the rate of anomerisation.