PRESENTATION BY Professor Ulf Hanefeld Delft University of Technology The Netherlands
PRESENTATION TITLE Flowing from Ester Synthesis in Water to Chirality
ABSTRACT The synthesis of esters is a standard reaction and is commonly performed with an acid chloride, a strong base such as pyridine and an alcohol. Alternatively, concentrated mineral acids are used as catalysts but they are, in most cases, not recycled. Overall, relatively harsh reaction conditions are required and low selectivity is thus observed. Recently, an acyltransferase from Mycobacterium smegmatis (MsAcT) was described. MsAcT was reported to catalyse ester formation in water when using ethyl acetate as co-solvent.1,2 This enzyme is a serine hydrolase with the characteristic Ser-His-Asp catalytic triad and similar to thioesterases and lipases it has a hydrophobic active site. In contrast to in particular lipases, MsAcT is not monomeric but an octamer. The hydrophobic tunnel leading to the active site is composed of amino acids of three of the eight monomers.
Here the production and application of the immobilised enzyme in a model system will be described. Starting from primary diols with ethyl acetate as co-solvent, diesters were synthesised. A continuous process was developed and flow rates allowed control of product distribution.3 A systematic investigation of the scope of this enzyme for the synthesis of esters in water revealed that primary alcohols are converted into esters in water using either ethyl acetate or vinyl acetate as acyl donor. This reaction is very clean and environmentally benign, having the potential to displace the classical acetic anhydride plus pyridine approach. While tertiary alcohols are not converted, secondary alcohols are accepted by MsAcT, albeit at lower rates compared to primary alcohols.4 Recent kinetic studies show all of these ester syntheses in water to be kinetically controlled.
This knowledge of flow chemistry was applied to the chiral synthesis of cyanohydrins using the oldest known enantioselective reaction, the hydroxynitrile lyase catalysed synthesis of mandelonitrile.5
1 I. Mathews, M. Soltis, M. Saldajeno, G. Ganshaw, R. Sala, W. Weyler, M. A. Cervin, G. Whited, R. Bott, Biochemistry 2007, 46, 8969.
2 L. Wiermans, S. Hofzumahaus, C. Schotten, L. Weigand, M. Schallmey, A. Schallmey, P. Domínguez de María, ChemCatChem 2013, 5, 3719.
3 K. Szymańska, K. Odrozek, A. Zniszczoł, G. Torrelo, V. Resch, U. Hanefeld, A. B. Jarzębski, Catal. Sci. Technol., 2016, 6, 4882.
4 N. de Leeuw, G. Torrelo, C. Bisterfeld, V. Resch, L. Mestrom, E. Straulino, L. van der Weel, U. Hanefeld, Adv. Synth. Catal. 2018, 360, 242.
5 L. Rosenthaler, Biochem. Z., 1908, 14, 238–25.
ABOUT THE PRESENTER
Ulf Hanefeld studied Chemistry in Göttingen. In 1993 he received his PhD from the Georg-August-Universität
zu Göttingen, having performed the research with Professor H. Laatsch (Göttingen) and as a DAAD fellow with Professor H. G. Floss (Seattle). After postdoctoral years with Professor C.
W. Rees (Imperial College London), Professor J. Staunton (Cambridge) and Professor J. J. Heijnen and Dr. A. J. J. Straathof (TU Delft), he received a fellowship from the Royal Netherlands Academy of Arts and Sciences (KNAW). He rose through the ranks at the Technische Universiteit Delft and his research in Delft focuses on enzymes, in particular HNLs, their immobilisation and application in organic synthesis. More recently the immobilisation was also applied in Flow Chemistry. Together with Roger Sheldon and Isabel Arends he wrote the book “Green Chemistry and Catalysis” and more recently he edited together with Leon Lefferts “Catalysis: An Integrated Textbook for Students”.
Tea/coffee will be available at 15h15
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