Mimicry of the proton wire mechanism of enzymes inside a supramolecular capsule enables β-selective O-glycosylations

Abstract

Enzymes achieve high substrate and product selectivities by orientating and activating the substrate(s) appropriately inside a confined and finely optimized binding pocket. Enzyme catalysis is generally regarded as the ultimate role model for chemical catalysis, and some basic aspects of enzymes have already been mimicked successfully with man-made catalysts. One fascinating facet of substrate activation inside enzyme pockets, which has not been mimicked with man-made catalysts so far, involves proton wires. 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 selective glycosylation reactions. Extensive control experiments provide very strong evidence that the reactions take place inside the molecular container. The communicating dual activation mode enabled by the proton wire is, to our knowledge, unknown in supramolecular and molecular catalysis so far.Enzymes have functioned as role models for chemists working in the broad field of catalysis. They enable conversions in an aqueous environment by binding the substrate(s) inside a hydrophobic binding pocket. The finely optimized environment of such binding pockets facilitates the highly selective conversion by orientating and activating the substrate(s) appropriately. Some aspects of enzymes, for instance, the binding pocket, have already been mimicked successfully with

Protection and Transformation of Natural Products within Aqueous Metal‐Organic Cages

“…The large resorcin[4]arene capsule 30 (volume of ca . 1400 Å 3 ) has been extensively applied by this team to the catalytic conversion of natural products and related congeners with remarkable results in organic solvent [32,33,72] . Capsule 30 assembles from six units of resorcin[4]arene 31 and eight molecules of water linked by sixty soft hydrogen bonds.…”

“…1400 Å 3 ) has been extensively applied by this team to the catalytic conversion of natural products and related congeners with remarkable results in organic solvent. [32,33,72] Capsule 30 assembles from six units of resorcin [4]arene 31 and eight molecules of water linked by sixty soft hydrogen bonds. The achiral 31 building block forms 30 as a racemic capsule mixture; however, they fast interconvert (racemize, Figure 8c).…”

Supramolecular Capsule-Catalyzed Highly β-Selective Furanosylation Independent of the SN1/SN2 Reaction Pathway

“…For low nucleophile concentrations (0.025−0.10 M), a reaction order of 0.26 was observed (Figure 4B), while we observed a value of 1.03 for the pyranosylation reaction. 38 Accordingly, the furanosylation mechanism is clearly shifted toward an S N 1 reaction on the mechanistic continuum between the prototypical S N 1 and S N 2 substitution types as compared to the pyranosylation reaction inside catalyst I. 57 Interestingly, the exact mechanism seems to depend on the reaction partners, as with MeOH as the acceptor, a reaction order of 0.82 was observed (see the Supporting Information, Section 9.6).…”

Fullerene Complexation in a Hydrogen-Bonded Porphyrin Receptor via Induced-Fit: Cooperative Action of Tautomerization and C–H···π Interactions

“…The modulation of the host–guest chemistry by means of extending beyond simple covalent adjustment of the cavity size represents a highly sought-after strategy to construct dynamic supramolecular receptors that are reminiscent of enzymes. − In nature, induced-fit, , conformational selection, , and allosteric control, − all operating by conformational changes of the host in response to the guest or other stimuli present, are the principles governing the substrate binding, activation, or remote control of the binding itself. Structural plasticity is also central to protein–protein recognition .…”