Date of Award:

5-2009

Document Type:

Dissertation

Degree Name:

Doctor of Philosophy (PhD)

Department:

Chemistry and Biochemistry

Committee Chair(s)

Cheng-Wei Tom Chang

Committee

Cheng-Wei Tom Chang

Committee

Alvan Hengge

Committee

Bradley S. Davidson

Committee

Robert S. Brown

Committee

Jon Y. Takemoto

Abstract

Oligomannosides prevalently exist as cell surface antigens. They play important roles in diseases such as viral infection and cancer, and they have been shown to be useful as candidates for vaccines. HIV, one of the most devastating modern diseases, has a high content of mannose sugars on its envelope glycoprotein gp120. Oligomannosides of the HIV virus, also called Man9, which are found on the glycoprotein gp120, have been shown to play a protective role for the HIV virus, shielding highly conserved protein domains of gp120 from proteolytic attacks. Thus gp120 plays an important role in HIV infection of cells, being responsible for the attachment and penetration of cells to be infected and is thus the target for immunotherapy or vaccine development. The synthesis of complex oligomannosides is still very challenging as numerous methods have been reported but not all are very reproducible.

The use of sonication as a new methodology tool for the synthesis of oligomannosides was investigated. A convenient sonication-mediated protocol applicable to glycosylation was developed. The synthesis of oligomannosides such as Man3, Man6, and Man9, was achieved under sonication conditions. The use of less reactive or so-called "disarmed" mannopyranosyl donors, such as acyl and thiophenyl donors, was investigated and interestingly the results gave good yields. These disarmed donors are easy to synthesize but it is difficult to perform glycosylation using traditional methods (low yields and longer reaction time). A fast and convenient method for the synthesis of this compound will be very beneficial in this field. Also, the investigation of the solid phase synthesis of carbohydrates under sonication conditions was conducted and the preliminary results were good.

The research investigated a new methodology for the synthesis of complex oligomannosides and oligosaccharides in general and also to improve the glycosylation process where necessary by using sonication methodology and thus establishing an accessible route for the solid phase synthesis of these compounds.

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Included in

Chemistry Commons

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