Access Type
Open Access Dissertation
Date of Award
January 2018
Degree Type
Dissertation
Degree Name
Ph.D.
Department
Chemistry
First Advisor
David Crich
Abstract
This dissertation presents the design and synthesis of oligo-(3,5-dithio-β-D-glucopyranoside) as β-(1 → 3)-D-glucan mimetics. The synthesized dimeric, trimeric and tetrameric mimetics were tested for their binding affinities to Dectin-1 and CR3 and their abilities to activate phagocytosis and pinocytosis.
The first chapter gives an introduction of β-(1 → 3)-D-glucan. It gives an introduction about the structure and origin of β-(1 → 3)-D-glucan as well as the immunostimulating effect of natural β-(1 → 3)-D-glucan. The study of interaction between β-(1 → 3)-D-glucan and the receptors leads to a conclusion that the hydrophobicity of β-(1 → 3)-D-glucan is crucial to its immunostimulating effect. Based on this conclusion, we designed the oligo-(3,5-dithio-β-D-glucopyranoside) as β-(1 → 3)-D-glucan mimetics.
The second chapter presents the synthesis study of oligo-(3,5-dithio-β-D-glucopyranoside). After a brief introduction of the synthesis of S-linked oligosaccharide, we talked about the synthesis of the 3,5-dithio-glucopyranoside as the monosaccharide building block. It presents the rearrangement product during the synthesis of 3,5-dithio-glucopyranoside and how to avoid the rearrangement to synthesize 3,5-dithio-glucopyranoside. After the monosaccharide synthesis, we talked about the S-glycosylation study of 3,5-dithio-glucopyranoside and how to synthesize the oligo-(3,5-dithio-β-D-glucopyranoside). Finally, the biological study of synthesized dimeric, trimeric and tetrameric mimetics was presented, which includes their binding affinities to Dectin-1 and CR3 and their abilities to stimulate the phagocytosis and pinocytosis.
Chapter three introduces p-N,N-dimethylamino benzyl (PDMAB) protecting group as a new protecting group. The novelty of PDMAB protecting group is that the deprotection can be achieved by microwave irradiation without any additives. We talked about the installation of PDMAB group and its application in the NIS / TMSOTf promoted glycosylation.
Finally, chapter four presents the experimental procedures of all the compound and the characterization data.
Recommended Citation
Liao, Xiaoxiao, "Design And Synthesis Of Oligo-(3,5-Dithio-Β-D-Glucopyranoside) As Β-(1→3)-Glucan Mimetics" (2018). Wayne State University Dissertations. 2111.
https://digitalcommons.wayne.edu/oa_dissertations/2111