Although glycochemistry has developed in leaps and bounds in the last two decades, the synthesis of a complex oligosaccharide or of a glycoconjugate remains a very challenging albeit critically important task. The difficulties inherent in such syntheses arise because of numerous reasons that center on the complexity of the chemistry when compared to that of oligonucleotide and peptide synthesis. The most important reactions in any oligosaccharide synthesis are the formation of the glycosidic bonds and there exists an absolutely overwhelming number of methods toward this end. Unfortunately, the vast majority of these methods have been developed empirically, are therefore underpinned by very little detailed understanding of mechanism, and have very little generality. The underlying theme of this proposal is that the challenge of the simplification of complex oligosaccharide synthesis is best met by an improved understanding of the mechanisms of glycosidic bond formation, coupled with the development of more efficient, straightforward and general mechanism-based methods. A necessary step toward this goal is the detailed investigation of the mechanisms of glycosylation mechanisms, and accordingly this proposal addresses several issues considered critical to the resolution of this problem. The issues to be addressed include i) the development of cation clock methods for the determination of reaction kinetics in sialic acid and furanoside glycosidic bond formation. ii) The determination of the interplay of the side chain conformation and of protecting groups and their combined influence on glycosylation stereoselectivity. iii) The development of methods for the efficient synthesis of the microbial sialic acids, legionaminic acid and pseudaminic acid, and of their glycosides. iv) The development of novel methods for the synthesis of C5 modified sialic acids by stereocontrolled substitutive deamination.