Carbohydrate-containing polymers and macrocycles

This dissertation focuses on the incorporation of carbohydrates as scaffolds for building multivalent architectures and chiral macrocycles. Multivalent interactions---particularly those between protein receptors and their carbohydrate epitopes---are an important fundamental phenomenon in Nature. Supramolecular chemistry not only utilizes multivalency (Chapter 1 ) to construct elaborate molecular architectures, but it also provides wholly synthetic model systems which can shed light on how biological processes may work in Nature. An understanding of the concept of multivalency can only be beneficial to the nanosciences and materials chemistry, as well, in constructing new materials. In order to probe multivalent interactions in biological systems, however, well-defined neoglycoconjugates displaying multiple glycoside residues, are necessary. Thus, protocols for the synthesis of lactoside-bearing glycodendrons and glycoclusters, whose structures are entirely made up of carbohydrates, were developed (Chapter 2). Photoaddition and reductive amination protocols were employed to synthesize well-defined di-, tri-, and tetravalent lactosides under mild conditions in a chemoselective manner. While these glycodendrons and glycoclusters present their lactoside ligands at fixed distances, dynamic multivalent neoglycoconjugates, display their ligands (Chapter 3) in an adjustable manner, such that the distances and orientation of the saccharide ligands are flexible. These self-assembled superstructures are comprised of lactoside-bearing cyclodextrins threaded onto a linear polymer chain in aqueous solution. Interestingly, these dynamic structures were found to be much more effective (on a per saccharide basis) in binding to Galectin-1 than their covalently-bound counterparts. In extending the concept of dynamic multivalent structures further, polyrotaxanes for binding Sialoadhesin were investigated (Chapter 4). The slippage approach was found to be an effective method for the synthesis of kinetically-fixed polyrotaxanes, stable at ambient temperatures. Finally, the regioselective and diastereoselective amplifications of chiral macrocycles from dynamic combinatorial libraries were investigated (Chapter 5). Dynamic covalent chemistry, in the form of acid-catalyzed transacetalations, was used to form dynamic combinatorial virtual libraries that were influenced by cesium or dibenzylammonium ions as templates. Indeed, the configurational, conformational, and constitutional variety inherent within the carbohydrates provide an infinite number of building blocks for creating multivalent scaffolds and macrocycles.