Abstract
This account describes our efforts aimed toward the discovery of original glycomimetics that target protein misfolding to fight rare diseases, with a focus on cystic fibrosis and Gaucher disease. The pursuit of this goal has led to promising leads and strategies, with the first description of a multivalent effect for correcting protein-folding defects in cells, and has also driven unexpected progress in synthetic methodology.
1 Introduction
2 The Therapeutic Targets: Challenges and Stakes
2.1 Glycosphingolipid Lysosomal Storage Disorders
2.2 Cystic Fibrosis
3 Synthetic Targets Met, Potent Leads Gained
3.1 Synthetic Targets Met
3.2 A First Detour via a Substrate Reduction Therapy Approach
3.3 Potent Leads Gained
4 Synthetic Targets Missed, Synthetic Progress Gained
4.1 A New Domino Reaction
4.2 Extending the Scope of C–H Amination
4.3 A New Versatile Amino Protecting Group
5 Multivalency: A New and Promising Approach
5.1 How It Began
5.2 Gaucher Disease
5.3 Cystic Fibrosis
6 Conclusion
Key words
carbohydrates - tandem reactions - C–H functionalization - multivalency - glycosidases
