Project description

Carbohydrates (sugars) are ubiquitous in the living cell and fulfill essential roles. Our immune system recognizes carbohydrates as self or foreign, and viruses recognize human cell-surface glycolipids as entrance points for infection.  Also in medicine, carbohydrates play important roles as anti-infectives, and in vaccines for instance.

In nature, enzymes modify carbohydrates into an immense array of molecules. Evolutionary, many of these transformations use radical processes, which is rather distinctive for carbohydrate metabolism, and a number of these transformations, that possess exquisite selectivity, are among the most beautiful reactions known.

On the contrary, the organic chemist starts from readily available monosaccharides and applies protecting groups which single out one hydroxy group, either for modification or to connect another protected monosaccharide. After all modifications and bond formations have taken place, the protecting groups are removed and the product is obtained. The large majority of these reactions uses polar chemistry.

Our group contributes significantly to recent developments in (photoredox) catalysis and electrochemistry that allow modification of carbohydrates in a site-selective manner without protecting groups. Most of these processes are radical reactions and are inspired by radical-based enzymatic mechanisms. In the first part of the current proposal, we aim to use photoredox catalysis for the incorporation of thiols in carbohydrates. This allows the synthesis of (natural) thioglycosides, which is important as thioglycosides resist enzymatic degradation. In the second part of the proposal we will use site-selectively modified sucrose (table sugar) as substrate for sucrases; enzymes that use sucrose for the synthesis of oligosaccharides. This allows the modification of carbohydrates and glycopeptides by adding a modified glucose residue. This builds a bridge between chemical and enzymatic oligosaccharide modification, allowing to combine strengths of both disciplines.

Additional specifications

We seek a candidate with an MSc in Chemistry, particularly in Organic Synthesis.