Polyfluoro-Pyridyl Glycosyl donors

Abstract

Carbohydrates are one of the most structurally and functionally diverse classes of naturally occurring compounds and it is well established that they play an essential role in a vast array of biological processes. The synthesis of stereochemically defined oligosaccharides by a series of glycosylation processes, involving the reaction between a glycosyl donor and acceptor, is of paramount importance in synthetic carbohydrate chemistry and glycobiology. However, despite the importance of glycosylation chemistry and the development of sophisticated methodologies, there remains no general and stereoselective strategy that has been universally adopted for the syntheses of oligosaccharides. In this thesis we present the synthesis and function of a novel family of glycosyl donors, in which fluorinated pyridine systems are utilised as the leaving group. In systems of this type it proved possible to 'tune' the glycosylation capability of the donor via variation of the substituents present on the pyridine ring and the type of Lewis acid activator used. The formation of a glycosidic bond with control of the stereochemistry at the anomeric centre is usually difficult. Interestingly glycosyl donor systems of this type provide a high degree of stereoselectivity, providing diastereomeric excesses in the region of 80 to 98%. It has been determined that polyfluoro-pyridyl glycosyl donors do not react via the established Sn1 glycosylation process but via an unique Sn2 process which gives rise to the high degree of stereoselectivity observed.