Studies Undertaken Towards the Total Synthesis of Antifreeze Compounds Based on the Xylomannan Antifreeze from the Alaskan Beetle Upis ceramboides

Abstract

Biological antifreeze substances are widely found in the tissues of cold-blooded organisms indigenous to polar environments. Prior to 2009, all these compounds were associated with protein, leading to the widespread assumption that all biological antifreeze substances must possess a protein or peptide core. This perception was dispelled by Duman and co-workers in 2009, whose discovery of a protein-free xylomannan-based antifreeze glycolipid from the Alaskan Beetle Upis ceramboides heralded a new class of biological antifreeze. Though the structure of the xylomannan has been known for over a decade, no one has yet to address several questions regarding the identity of lipid component, the size of the xylomannan portion and the influence of these two factors in the overall antifreeze activity. To undertake such investigations, a library of structurally well-defined glycolipid mimetics will be required, and these are typically achieved through total chemical synthesis. Each compound will differ in both the number of disaccharide repeating units (between one to five units), and three different hydrophobic aglycones selected in lieu of the unidentified lipid component. Consequently, a total of fifteen compounds will be synthesized. A major challenge in this project is the synthesis of each beta-mannosidic linkage in the xylomannan portion. Moreover, beta-mannosylation as a means of glycan chain assembly remains relatively less explored. Therefore the ulosyl bromide approach was selected to investigate such a possibility. This was successfully demonstrated in the synthesis of xylomannan disaccharides; however, issues inherent to this approach led to the search for another alternative. In the second approach, a simultaneous multiple C-2 inversion strategy was developed as a convenient way to assemble all the oligosaccharides. The strategy developed involves the use of beta-glucosylation in assembling the glycan chain, followed by simultaneous C-2 inversion to convert all the glucose residues into the beta-mannosides. This was successfully demonstrated in the synthesis of all the target fifteen compounds, which will then be delivered to lab of Prof. Hubbard (Department of Chemistry, University of Alberta) for assessment of antifreeze activity.