Document Type

Dissertation

Degree

Doctor of Philosophy

Major

Chemistry

Date of Defense

7-11-2017

Graduate Advisor

Alexei V. Demchenko

Committee

L. Douglas Smith

Bruce Hamper

Keith Stine

Abstract

Carbohydrates are the most abundant molecules on Earth. They are involved in a wide range of fundamental biological processes: anti-inflammation, immune response, joint lubrication, cell growth, antigenic determination. Carbohydrates are also held responsible for many damaging cellular processes, such as bacterial and viral infections, development of tumors, etc.. Therefore, the development of effective methods for the synthesis of complex carbohydrates has become a critical area of glycosciences. One challenge that stands out is the stereocontrol in the synthesis of glycosidic bonds, the linkage that serves as the only means to connect simple monosaccharides into complex oligomeric networks. Beyond this, the lack of a simple automated platform, similar to that utilized in the preparation of oligonucleotides and oligopeptides, significantly hampers access to oligosaccharides. The work presented herein addresses both of these limitations of oligosaccharides synthesis: stereocontrol and the lack of automation. The stereocontrolled formation of very challenging betamannosidic linkages has been achieved using a new reaction called Hydrogen-bondmediated Aglycone Delivery (HAD). Automation in Oligosaccharide solid phase synthesis has been accomplished using an AgilentTM HPLC, model 1260 Infinity, that was adapted to the polymer supported synthesis of oligosaccharides. The utility of the HAD reaction and the HPLC-based automated technology has been demonstrated by the synthesis of different oligosaccharide sequences in high stereoselectivities and yields.

Included in

Chemistry Commons

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