Methods for 1,2-Cis-Selective O-Glycosylation and Synthesis of an A. baumannii Lipooligosaccharide Core Disaccharide

Abstract

This dissertation focuses on the formation of organic thin films on gold surfaces and synthesis of oligosaccharides. Chapter one, is a brief introduction on the utility of thin films, as well as ways to characterize thin films, as well as, a report on the attempt to form organic thin films on Au(111) surfaces using photoredox catalysis. Glycoconjugates on cell surfaces serve as important mediators of intercellular recognition, adhesion, and viral infection. Due to the significant role that glycoconjugates play on the surface of cells, oligosaccharide synthesis is of great interest. Chapter two, is an extensive review of oligosaccharide synthesis, its importance, and glycosylation methods. There are several methods to form complex oligosaccharides; however, chapter three focuses on the orthogonal synthesis of a trisaccharide using temperature control. The main challenge in the synthesis of biologically relevant oligosaccharides is the development of stereoselective glycosylation reactions. Methods to form the 1,2-trans glycosidic linkages (beta) have been developed with the help of neighboring group participation of acyl protecting groups in the C2 position. However, protocols for selective synthesis of 1,2-cis glycosidic linkages (alpha) has proven to be difficult due to low yields and poor selectivity. To circumvent these difficulties, protecting group manipulation has been employed to form 1,2-cis glycosidic linkages through a SN2-like mechanism. Electron withdrawing groups have shown to play an important role in aiding in the formation of 1,2-cis linkages. Thus, in chapter four, methods to selectively form 1,2-cis linkages using thioglycosides and acetimidates armed with varying electron withdrawing groups is discussed. Chapter five focuses on the application of oligosaccharide synthesis with the development of a glycoconjugate vaccine for Acinetobacter baumannii. A. baumannii is a common cause of infections associated with ICU residence, traumatic injury, mechanical ventilation, and neurosurgery. Vaccine development is an important preventative measure due to the increasing antibiotic resistance of A. baumannii strains. The proposed vaccine consists of a pentasaccharide portion of an A. baumannii lipooligosaccharide to be conjugated to a carrier molecule. Progress toward the synthesis of the pentasaccharide portion of the proposed glycoconjugate vaccine is discussed in this chapter.