A research program devoted to the development of a new, direct dehydrative glycosylation method for the synthesis of complex oligosaccharides and glycoconjugates is proposed. The method involves in situ activation of the hemiacetal hydroxyl of a glycosyl donor with electrophilic, activated sulfoxide reagents, allowing for single step glycosylations with 1- hydroxyl glycosyl donors. Investigations into the score, mechanism, and catalytic potential of this new reaction should lead to a powerful and versatile stereoselective glycosylation reaction that can be applied to the synthesis of natural and non-natural oligosaccharides of biological utility. The application of the proposed dehydrative glycosidic coupling method to polymer-supported iterative oligosaccharide synthesis will be investigated. Successful development of this strategy should allow for single-step coupling iterations on the polymer support for the efficient construction of oligoscaccharides. Direct application of this glycosylation method for the synthesis of bioactive complex oligosaccharides is also proposed. Emphasis is directed toward the synthesis of immunostimulating agents, including: (1) the powerful adjuvant QS-21A; and (2) bioconjugatable oligosaccharides of the tumor gangliosides 9-O-acetyl-GD3 and N-glycoylyl-GM3 for potential use as subunit antigens in cancer vaccine development. The full development of this carbohydrate synthesis research program should greatly facilitate the use of these and other synthetic oligosaccharides of immunologic diagnosis and vaccine therapies.
Showing the most recent 10 out of 37 publications
