A research program devoted to the development of new methods for the synthesis of complex oligosaccharides and glycoconjugates is proposed. The methods involve the development of new reagents for glycosidic bond formation, including sulfoxide-mediated dehydrative glycosylation, sulfide-mediated dehydrative glycosylation, 2-hydroxyglycosylation with glycals, and 2-amidoglycosylation with glycals. All of these methods involve novel reagents and reaction pathways for dehydrative coupling, oxygen transfer, and nitrogen transfer. Investigations into the scope and mechanism of these new reactions should lead to a series of powerful glycosylation methods that can be applied to the synthesis of natural and non-natural oligosaccharides of biological utility. Direct application of these glycosylation methods for the synthesis of bioactive complex oligosaccharides is also proposed. In this research program, emphasis is directed toward our synthetic efforts in the synthesis of immunostimulating agents including: (1) the powerful adjuvant QS-2 1 A; and (2) bioconjugatable oligosaccharides of the tumor gangliosides N-glycolyl-GM3 and Sle a 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 for immunologic diagnosis and vaccine therapies.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
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Medicinal Chemistry Study Section (MCHA)
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Schwab, John M
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University of Illinois Urbana-Champaign
Schools of Arts and Sciences
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Karimov, Rashad R; Tan, Derek S; Gin, David Y (2018) Synthesis of the hexacyclic triterpene core of the jujuboside saponins via tandem Wolff rearrangement-intramolecular ketene hetero-Diels-Alder reaction. Tetrahedron 74:3370-3383
Karimov, Rashad R; Tan, Derek S; Gin, David Y (2017) Rapid assembly of the doubly-branched pentasaccharide domain of the immunoadjuvant jujuboside A via convergent B(C6F5)3-catalyzed glycosylation of sterically-hindered precursors. Chem Commun (Camb) 53:5838-5841
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