Studies of Lewis acid promoted anomerisation reactions

Abstract

The stereoselective synthesis of the glycosidic bond still remains a challenge for the synthetic carbohydrate chemist. Lewis acid promoted anomerisation offers a useful means of generating 1,2-cis glycosides from their 1,2-trans counterparts. The main aim of this thesis is the study of anomerisation reactions and the factors affecting them. Previously The Murphy group has reported the anomerisation of a variety of glycosides, however it is hoped that a greater understanding of factors affecting the anomerisation reaction may enhance its synthetic utility. Chapter 2 involves the study of the role of the C-2 benzoate in the Lewis acid promoted anomerisation of benzoylated glycosides. Previous studies showed rate enhancements when a benzoate was present at the C-2 position and this was proposed to be due to resonance effects. A variety of para substituted benzoates at the C-2 position were synthesized and their rates of anomerisation determined. Hammett and Swain-Lupton plots were generated using the data generated. Chapter 3 details the study of the effect of conformation in the anomerisation reaction. Previously, rate enhancements were observed in the anomerisation of butyl glucopyranosides which were armed with bulky silyl groups. A series of galactopyranosides were synthesized to investigate if the α-anomers could be obtained from their β counterparts and if arming these with silyl groups resulted in enhanced reactivity. Efforts towards the synthesis of a reactant with a carboxylate at the C-3 position are also described. Chapter 4 describes the application of anomerisation in the synthesis of aromatic S-glycosides. Both the α and β anomers of thioglycosides have previously shown to be galectin inhibitors and anomerisation offers a means to generate the α-anomers. Glycosyl thiol anomerisation was found to be an efficient means towards α-thiopyridyl linkages as well as in the synthesis of other compounds.