Immunity, cell growth, cell-cell communication and inflammation are among the numerous biological processes influenced by complex carbohydrates. However, unlike other classes of bio-macromolecules such as proteins or nucleic acids, the biosynthesis of complex oligosaccharides is not under direct transcriptional control. Moreover, the functional diversity within naturally occurring monosaccharides presents the possibility of generating countless constitutional and stereochemical isomers upon their covalent combination to form complex oligosaccharides. These factors make it extremely difficult to access tractable homogeneous quantities of oligosaccharides for biological evaluation. Consequently, the development of new methods for the chemical synthesis of oligosaccharides and their conjugation with other macromolecular entities is a principle focus in organic synthesis.
Among the most important reactions in carbohydrate synthesis is the formation of the glycosidic bond since it is the primary means by which monosaccharide building blocks are assembled into more complex oligosaccharide structures. We have developed a series of new methods for complex oligosaccharide construction. These include several direct dehydrative glycosylations employing 1-hydroxy glycosyl donors. In addition, we have established a number of oxidative glycosylation reactions with glycal carbohydrate donors, in which novel modes of oxygen- and nitrogen-transfer processes have been uncovered. We will continue to define the scope and limitations of all of our new synthetic methods in their application to complex molecule synthesis, with particular emphasis on glycoconjugate immunostimulating agents.