Enzymes achieve high substrate and product selectivities by orientating and activating the substrate(s) appropriately inside a confined and finely optimized binding pocket. Although some basic aspects of enzymes have already been mimicked successfully with man-made catalysts, substrate activation by proton wires inside enzyme pockets has not been recreated with man-made catalysts so far. A proton wire facilitates the dual activation of a nucleophile and an electrophile via a reciprocal proton transfer, enabling highly stereoselective reactions under mild conditions. Here we present evidence for such an activation mode inside the supramolecular resorcin[4]arene capsule and demonstrate that it enables catalytic and highly β-selective glycosylation reactions—still a major challenge in glycosylation chemistry. Extensive control experiments provide very strong evidence that the reactions take place inside the molecular container. We show that this activation strategy is compatible with a broad scope of glycoside donors and nucleophiles, and is only limited by the cavity size. [Figure not available: see fulltext.]
Mimicry of the proton wire mechanism of enzymes inside a supramolecular capsule enables β-selective O-glycosylations / Li, T. -R.; Huck, F.; Piccini, G.; Tiefenbacher, K.. - In: NATURE CHEMISTRY. - ISSN 1755-4330. - 14:9(2022), pp. 985-994. [10.1038/s41557-022-00981-6]
Mimicry of the proton wire mechanism of enzymes inside a supramolecular capsule enables β-selective O-glycosylations
Piccini G.;
2022
Abstract
Enzymes achieve high substrate and product selectivities by orientating and activating the substrate(s) appropriately inside a confined and finely optimized binding pocket. Although some basic aspects of enzymes have already been mimicked successfully with man-made catalysts, substrate activation by proton wires inside enzyme pockets has not been recreated with man-made catalysts so far. A proton wire facilitates the dual activation of a nucleophile and an electrophile via a reciprocal proton transfer, enabling highly stereoselective reactions under mild conditions. Here we present evidence for such an activation mode inside the supramolecular resorcin[4]arene capsule and demonstrate that it enables catalytic and highly β-selective glycosylation reactions—still a major challenge in glycosylation chemistry. Extensive control experiments provide very strong evidence that the reactions take place inside the molecular container. We show that this activation strategy is compatible with a broad scope of glycoside donors and nucleophiles, and is only limited by the cavity size. [Figure not available: see fulltext.]File | Dimensione | Formato | |
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