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The synthesis of small molecules able to mimic the active site of hydrolytic enzymes has been largely pursued in recent decades. The high reaction rates and specificity shown by natural hydrolases present an attractive target, and yet the preparation of suitable small‐molecule mimics remains challenging, requiring activated substrates to achieve productive outcomes. Here we present small synthetic artificial enzymes which mimic the catalytic site and the oxyanion hole of chymotrypsin and N‐terminal hydrolases and are able to perform, for the first time, the transesterification of a non‐activated ester such as ethyl acetate with methanol under mild and neutral reaction conditions. [ABSTRACT FROM AUTHOR]

Cleft type receptors showing the oxyanion hole motif have been prepared in a straightforward synthesis starting from the commercial 3,7‐dihidroxy‐2‐naphthoic acid. The double H‐bond donor pattern is achieved by the introduction of a sulfonamide group in the C‐8 position of naphthalene and a carboxamide at the C‐2 position. This cleft, for which the geometry resembles that of an oxyanion hole, is able to adjust to different guests, as shown by the analysis of the X‐ray crystal structures of associates with methanol or acetic acid. Combination of hydrogen bonds and charge‐transfer interactions led to further stabilization of the complexes, in which the electron‐rich aromatic ring of the receptor was close in space to the electron‐deficient dinitroaromatic guests. Modelling studies and bidimensional NMR experiments have been carried out to provide additional information. [ABSTRACT FROM AUTHOR]

Back Cover: Transesterification of Non-Activated Esters Promoted by Small Molecules Mimicking the Active Site of Hydrolases (Angew. Keywords: Artificial Hydrolase; Enzyme Mimic; Organocatalysis; Oxyanion Hole; Transesterification EN Artificial Hydrolase Enzyme Mimic Organocatalysis Oxyanion Hole Transesterification 1 1 1 08/23/22 20220826 NES 220826 B A small synthetic artificial enzyme b is able to accomplish, for the first time, the transesterification of non-activated esters under neutral and mild conditions. Artificial Hydrolase, Enzyme Mimic, Organocatalysis, Oxyanion Hole, Transesterification. [Extracted from the article]

Keywords: Artificial Hydrolase; Enzyme Mimic; Organocatalysis; Oxyanion Hole; Transesterification EN Artificial Hydrolase Enzyme Mimic Organocatalysis Oxyanion Hole Transesterification 1 1 1 08/23/22 20220826 NES 220826 B Ein kleines synthetisches Enzym b ist erstmals in der Lage, die Umesterung von unaktivierten Estern unter neutralen und milden Bedingungen durchzuführen. Rücktitelbild: Transesterification of Non-Activated Esters Promoted by Small Molecules Mimicking the Active Site of Hydrolases (Angew. Inspiriert von der katalytischen Maschinerie von Chymotrypsin und N-terminalen Hydrolasen, zeigen José J. Garrido-González, Ángel L. Fuentes de Arriba et al. in ihrem Forschungsartikel (e202206072), dass ein kleines Molekül, das die katalytische Triade und das Oxyanionloch von Hydrolasen nachahmt, im Reagenzglas die katalytischen Eigenschaften hydrolytischer Enzyme nachbilden kann. [Extracted from the article]