Biocatalytic access to chiral amines and C-C bond formation
Prof Wolfgang Kroutil
Atom efficient and mild transformations are highly desired reactions for C-C bond formation as well as for the asymmetric preparation of amines. Various biocatalytic methods leading to optically pure amines have been developed, whereby in the lecture methods involving transaminases and lyases (e.g. Picter Spenglerases will be discussed. Transaminases have become an established method for the amination of ketones as a key step in the synthesis of active pharmaceutical ingredients. As an example for a synthetic application we report the regio- and stereoselective asymmetric mono-amination of a single ketone moiety out of three (see compound 1) which allowed performing the shortest and highest yielding total synthesis of the bicyclic showcase pyrrolizidine alkaloid xenovenine without the need for protecting strategies. For the synthesis of the blockbuster pregablin, we recently engineered various transaminases to achieve high optical purity of the product.
By searching metabolic pathways we identified enzymes suitable for Friedel-Crfts acylation, a reaction previously no associated with biocatalysis.
- G. Grogan, Curr. Opin. Chem. Biol. 2018, 43,15.
- R. C. Simon, B. Grischek, F. Zepeck, A. Steinreiber, F. Belaj, W. Kroutil, Angew. Chem. Int. Ed. 2012, 51, 6713.
- S. E. Payer, J. H. Schrittwieser, B. Grischek, R. C. Simon, W. Kroutil, Adv. Synth. Catal. 2016, 358, 444.
- C. S. Fuchs, J. E. Farnberger, G. Steinkellner, J. H. Sattler, M. Pickl, R. C. Simon, F. Zepeck, K. Gruber, W. Kroutil, Adv. Synth. Catal. 2018, 360, 768.
- N. G. Schmidt, T. Pavkov-Keller, N. Richter, B. Wiltschi, K. Gruber, W. Kroutil, Angew. Chem. Int. Ed. 2017, 56, 7615.