Plagiarizing Proteins: Enhancing Efficiency in Asymmetric Hydrogen‐Bonding Catalysis through Positive Cooperativity

Abstract

A new twist for a fold: Conformationally well‐defined thiourea catalysts, like that shown, stabilized by intramolecular hydrogen bonds demonstrate cooperative ligand–receptor binding. This conformation leads to significantly enhanced catalytic efficiency, resulting in higher turnover rates and lower catalyst loading whilst maintaining high enantioselectivity in a model reaction.

Cooperative Assistance in Bifunctional Organocatalysis: Enantioselective Mannich Reactions with Aliphatic and Aromatic Imines

“…As a result, only one of the hydrogen‐bond donors in the catalyst may be used for the activation of the electrophile,4a thus reducing the level of activation of the electrophile. We reasoned that the presence of an intramolecular hydrogen bond5 could provide significant improvement in the hydrogen‐bond‐donor capacity of the thiourea moiety through cooperative effects,6 as already demonstrated by Smith and co‐workers (catalyst C ; Scheme ) 5d…”

The Canonical Helix of Urea Oligomers at Atomic Resolution: Insights Into Folding‐Induced Axial Organization

“…Oligomers consisting of N , N ′‐linked urea bridging units are receiving increasing attention as folding backbones 9. 15–20 Peptidomimetic oligoureas belonging to the γ ‐peptide lineage,21 (‐NH‐CH(R i )‐CH 2 N′H‐CO) n ‐, have a remarkable propensity to fold into helical secondary structures in solution22–26 and show promise for interaction with biologically relevant targets 27. 28 Compared to γ‐peptides,5, 29, 30 helix stabilization in oligoureas is promoted by the presence of additional backbone conformational restriction and H‐bond donor sites.…”

“…31, 38 Our study also demonstrates the robustness of the folding process: four acyclic residues are sufficient to drive complete helix formation with all complementary H‐bonding sites being satisfied. Overall, this crystallographic data set provides the ground for the structure‐guided development of urea foldamers with function, such as recognition of biomolecules and catalysis,20, 39, 40 and also for the elaboration of new tertiary and quaternary structural motifs.…”

Enantioselective Cooperativity Between Intra‐Receptor Interactions and Guest Binding: Quantification of Reinforced Chiral Recognition

“…The behavior of the receptor 2 proves that reinforced molecular recognition can be achieved by much simpler systems than was initially thought. In addition it can also be concluded that reinforcement is not only a valid tool to improve receptors but also for favoring chiral discrimination, thus paving the way to a novel concept for asymmetric catalysis 33. 34 It is worth mentioning that up until now all the reported methods for improved chiral recognition are based either on a more rigid receptor or on bulkier chiral auxiliaries.…”