Synthesis of the S and C-linked diaccharide analogues related to hyaluronic acid

Author

Sean K. Hamilton

Date of Award

12-2001

Degree Type

Dissertation

Degree Name

Doctor of Philosophy

Major

Chemistry

Major Professor

David C. Baker

Committee Members

Richard M. Pagni, Ziling Xue, Naima Moustaid-Moussa

Abstract

Hyaluronic acid is a ubiquitous glycosaminoglycan found in several mammalian tissues. It has been implicated in the development and progression of cancer by interacting with a cell's CD 44 receptor. Our goal was to synthesize small molecules that are hyaluronic acid mimics, which contain CH2 and S groups strategically placed, as to render the molecules hydrolytically stable. Described in this dissertation are the synthetic efforts involved in assembling the disaccharide units related to hyaluronic acid that can potentially serve as building blocks for the synthesis of long-chain, enzymatically stable, oligosaccharide mimics. Both the S- and CH₂- linked disaccharide analogues proved synthetically formidable. However, they were successfully synthesized. The C-disaccharide, after several methods were attempted, was obtained from the coupling of a glycosyl tin derivative with an aldehyde derived from methyl α-D-glucopyranoside. The S-disaccharide was successfully accomplished through an S_N2 displacement of an axial triflate by a thiol.

Recommended Citation

Hamilton, Sean K., "Synthesis of the S and C-linked diaccharide analogues related to hyaluronic acid. " PhD diss., University of Tennessee, 2001.
https://trace.tennessee.edu/utk_graddiss/8517