From Sweet Molecular Giants to Square Sugars and Vice Versa

Abstract

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

An Unexpected Lewis Acid-Catalyzed Cascade during the Synthesis of the DEF-Benzoxocin Ring System of Nogalamycin and Menogaril: Mechanistic Elucidation by Intermediate Trapping Experiments and Density Functional Theory Studies

“…In contrast, much less work has been performed with bifunctional glycosides. − This may be explained by the fact that, if the sequential functionalization of the two reactive anomeric centers offers numerous synthetic opportunities, it also raises many challenges in terms of chemo-, regio-, and stereoselectivity. In conjunction with our continuing studies on glycomimetics, we have recently reported a convenient strategy for the synthesis of C -naphthyl ketosides by way of a reaction sequence involving hydrogen atom transfer (HAT)-mediated glycosylation of quinones with exo -glycals and BF 3 ·Et 2 O-catalyzed O → C glycoside rearrangement (Scheme ). …”