Date of Award

8-2005

Degree Type

Dissertation

Degree Name

Doctor of Philosophy

Major

Chemistry

Major Professor

David C. Baker

Committee Members

Richard Pagni, Ziling Xue, Marianne Breinig

Abstract

Hyaluronic acid is a viscous high MW polysaccharide that is synthesized in the plasma membrane. It is found in the connective tissue space, in the synovial fluid of movable joints and in the vitreous humor of the eye. Its chemical structure is composed of a repeating disaccharide unit in which D-glucuronic acid is linked to the 3-position of N-acetyl-D-glucosamine. It appears to play an important role in the metastasis of cancer cells since cancer cell’s CD44 receptors adhere to it and migrate to host cells. Our goal was to synthesize small HA-oligosaccharides that would behave as CD44 metastasis receptor antagonists. However, HA is degraded in the liver, in the lymph nodes, as well as in local tissues by acid hydrolases. Several lines of evidences have established that replacing the glycosidic –O– linkages with –CH2– linkages provides resistance to enzymatic cleavage. Since synthesizing an all –CH2– linked oligosaccharide is an arduous task and virtually intractable, it was decided to design hydrolase-resistant HA mimics by substituting the interglycosidic oxygen atom with the CH2-group at strategical positions. In this dissertation is described the synthesis of a –CH2– linked disaccharide to a methyl β-analog related to HA that can serve as a building block for the synthesis of long-chain, hydrolase-resistant oligosaccharide mimics. The C-disaccharide was acquired from coupling a glycosyl tin derivative with an aldehyde stemming from methyl β-D-glucopyranoside.

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