Design and transition metal -mediated synthesis of multivalent neoglycoconjugates bearing terminal galactosides with various valency and structural features

In the past ten years, with the emergency of multivalent neoglycoconjugates such as glycopolymers, glycodendrimers, and glycoclusters, carbohydrates have gained a lot of attention in the hope of developing potent carbohydrate-based therapeutics, as well as the opportunities to investigate glycobiology.;So far many strategies have been explored to effectively assemble multivalent neoglycoconjugates. This work contains a discussion of the design and transition metal-mediated synthesis of terminal galactoside-carrying glycoclusters and glycodendrimers in detail.;Propargyl alpha-galactoside antigen monomer was synthesized using conventional glycosidation methods. Then analogues of alpha-galactoside antigen clusters were prepared utilizing the Sonogashira reaction as the key step. Various conditions for the Sonogashira have been investigated and an interesting finding is that this reaction does occur with Cu (I). These synthetic alpha-galactoside antigens have shown enhanced binding affinity toward human anti-alpha-galactoside antigen antibodies in biochemical assays.;Likewise, galactoclusters were prepared as potential galectin inhibitors. However, these fully deprotected compounds were barely soluble in aqueous conditions. To solve this problem, analogues of lactoclusters, having an extra glucosyl residue, with various valencies and structural features were synthesized. Kinetic precipitation tests demonstrated that most lactoclusters cross-linked with galectin-3 formed insoluble complexes quickly and this phenomenon was observed for the first time, thus suggesting the clustering of the receptors upon contact.;A sequence of olefin cross-metathesis, Sonogashira reaction, and cyclotrimerization was performed to assemble a hexameric C-linked glycopeptidomemetic.;Olefin cross-metathesis mediated by the second generation Grubbs catalyst was successfully effected to prepare extended glycoallyl halides and unnatural amino acids. These glycoallyl halides were proven to be useful in the synthesis of high order glycoclusters.