Characterization of the Low- Energy Conformations of Seven Membered-Ring Oxacycles through Synthesis, Spectroscopy, and Computational Chemistry

Herein are described the synthesis and conformational analysis of new seven membered ring sugars referred to as septanosides. The Peczuh Group has developed several syntheses of septanosides with the ambition of mimicking natural pyranosides. To date, septanosides have been used to mimic the biological functionality of natural carbohydrates and provide mechanistic insight in organic synthesis. Both avenues rely on the conformational idiosyncrasies of carbohydrates. In general, carbohydrates interact with binding partners in their ground state conformation. One aim of the projects detailed in this thesis was to synthesize septanosides for the purpose of deciphering their ground state conformations in solution by utilizing NMR spectroscopy and in silico modeling.

Chemical glycosylation is the principal reaction for the preparation of glycomimetics. The naked oxocarbenium ion is the classical intermediate invoked in SN1 glycosylation. Nonetheless, this intermediate has a brief lifespan, and recent experiments indicate that its active form involves electrostatic stabilization via participating substituents or external factors such as triflate counter ions. Investigations of the cation engaged in glycosylation generated from fully substituted septanosyl donors have not been performed. Septanoses, which exhibit a diverse range of conformations, offer an interesting vantage point for studying glycosylation chemistry. A more profound comprehension of the chemical processes involved in septanose glycosylation can pave the way for the discovery of novel methods for synthesizing septanose glycomimetics.

The Ferrier rearrangement is a chemical reaction that demonstrates the challenges encountered in glycosylation with septanoses. This transformation involves converting a 1,2-unsaturated septanose – called a carbohydrate based oxepine – into a 2,3-unsaturated septanose, while simultaneously creating a new acetal linkage. Detailed in this dissertation is the examination of the Ferrier rearrangement from the perspective of the oxepine donor and the cationic intermediate using computational chemistry and spectroscopy.