Document Type

Dissertation

Degree

Doctor of Philosophy

Major

Chemistry

Date of Defense

3-20-2020

Graduate Advisor

Alexei V. Demchenko

Committee

Eike B. Bauer

Cristina De Meo

Keith J. Stine

Abstract

Carbohydrates or sugars are some of the most diverse and abundant biological molecules. They are involved in a multitude of processes in the body such as fertilization, cell-cell communication, and cancer metathesis. Because of these vital functions, the study of sugars is rapidly growing field. The field however is limited due to the complex nature of sugars which results in difficulties in obtaining large quantities for study.

Protecting group manipulation is a large emphasis area in carbohydrate chemistry due to the need to selectively protect different functional groups of each molecule during synthesis. Catalytic and selective cleavage of protecting groups is a growing area in the field of carbohydrates as current methods are time-consuming and require large excess of reagents. Picoloyl ester is becoming a common protecting group due to its ability to provide a powerful stereodirecting effect in glycosylation reaction. Chapter 2 details the development of a new catalytic approach to remove the picoloyl group in a highly chemoselective manner.

Protecting group manipulation is only one part of carbohydrate synthesis. New catalytic methods for glycosylation, a fundamental reaction for connecting two sugar units, are also needed. Chapter 3 describes our recent discovery that catalytic FeCl3 can efficiently activate glycosyl chloride to produce disaccharides in respectable yields in 30 min – 16 h. Chapter 4 further elaborates upon the topic of chemical glycosylation. Described herein is the application of a cooperative Ag2O and triflic acid catalysis to glycosidation of glycosyl chlorides. Fast reaction times and near quantitative yields are the main traits of this method.

Lastly, Chapter 5 combines findings described in the previous chapters into development of a new superior platform for oligosaccharide synthesis. Currently used strategies for oligosaccharide synthesis are time consuming, inefficient, and may lead to low yields of oligosaccharides. By combining the catalytic picoloyl group cleavage and activation of glycosyl chlorides using FeCl3 we developed a reverse orthogonal synthetic strategy which combined protecting group cleavage and activation of glycosyl donors in one step. We then showcase how efficiently this concept works for the rapid assembly of oligosaccharide sequences.

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