Document Type



Doctor of Philosophy


Chemistry, Organic

Date of Defense


Graduate Advisor

Prof. Alexei V. Demchenko, Ph.D.


Prof. Eike B. Bauer, Ph.D.

Prof. Bruce C. Hamper, Ph.D.

Prof. Keith J. Stine, Ph.D.


Stereocontrolled Mannosylation by Hydrogen-Bond-Mediated Aglycone Delivery

Carbohydrates are the essential bio-molecules of life as they form the forefront of interactions with receptors, proteins, pathogens, or neighboring cells. On cell-surfaces, carbohydrates are mostly found as linear or branched glycoconjugates, and a majority of them are linked via either 1,2-cis or 1,2-trans O-glycosidic linkages. There is no template-driven pathway for achieving the synthesis of glycans unlike other biomolecules like proteins and nucleic acids. The synthesis of 1,2-trans glycosides can be reliably achieved via the neighboring group assistance. The synthesis of 1,2-cis glycosides is difficult because, beyond weak anomeric effects, there are no forces helping in directing the stereoselectivity. The synthesis of β-mannosides is complicated further because the anomeric effect is working against it. Current methods for β-mannosylation require specialized donors and super-low temperatures.

Hydrogen-bond-mediated aglycone delivery (HAD) method introduced by our lab makes use of remote picolinyl and picoloyl groups that are capable of providing a strong stereodirecting effect.Among a variety of targets and substrates investigated, a highly stereoselective formation of β-mannosidescan be achieved via the assistance of the remote 3-O-picoloyl group. This thesis is dedicated to the synthesis of novel glycosyl donors directed for achieving challenging β-mannosidic linkages present in the oligosaccharides containing D-mannosamine (ManNAc), D-mannuronic acid (ManA), and D-mannosaminuronic acid (ManNAcA). These residues are quite abundant in the microbial glycans, wherein they are connected via β-(1,2-cis) linkages and are deemed essential in the development of carbohydrate-based drug-conjugates.