From Sweet Molecular Giants to Square Sugars and Vice Versa

This account describes our recent studies in the field of glycomimetics. Our efforts in understanding the structural basis of multivalent effects in glycosidase inhibition have led to decisive mechanistic insights supported by X-ray diffraction analyses and to the discovery of multimeric iminosugars displaying one of the largest binding enhancements reported so far for a non-polymeric enzyme inhibitor. Pushing the limits of the inhibitory multivalent effect has also driven progress in synthetic methodology. The unexpected observation of side products en route to the synthesis of our targets has been the starting point of several new synthetic methodologies, including metal-free deoxygenation of alcohols and one-pot double thioglycosylation. In parallel to our work on giant' neoglycoclusters, we have developed access to original constrained glycomimetics based on a 4-membered ring (square sugars'). Carbohydrates with a quaternary (pseudo)anomeric position were also synthesized from exo-glycals through catalytic hydrogen atom transfer and a novel oxidative radical-polar crossover process.1 Introduction2 Sweet Giants3 Multivalency Spin-Offs4 Sweet Curiosities4.1 Square Sugars4.2 From C,C-Glycosides to Formal Glycosylation of Quinones5 Conclusion