%0 Journal Article %1 C6OB02139E %A Weiß, M. S. %A Pavlidis, I. V. %A Spurr, P. %A Hanlon, S. P. %A Wirz, B. %A Iding, H. %A Bornscheuer, U. T. %D 2016 %I The Royal Society of Chemistry %J Org. Biomol. Chem. %K herberg myown %N 43 %P 10249-10254 %R 10.1039/C6OB02139E %T Protein-engineering of an amine transaminase for the stereoselective synthesis of a pharmaceutically relevant bicyclic amine %U http://dx.doi.org/10.1039/C6OB02139E %V 14 %X Application of amine transaminases (ATAs) for stereoselective amination of prochiral ketones represents an environmentally benign and economically attractive alternative to transition metal catalyzed asymmetric synthesis. However, the restrictive substrate scope has limited the conversion typically to non-sterically demanding scaffolds. Recently, we reported on the identification and design of fold class I ATAs that effect a highly selective asymmetric synthesis of a set of chiral aromatic bulky amines from the corresponding ketone precursors in high yield. However, for the specific amine synthetic approach extension targeted here, the selective formation of an exo- vs. endo-isomer, these biocatalysts required additional refinement. The chosen substrate (exo-3-amino-8-aza-bicyclo3.2.1oct-8-yl-phenyl-methanone), apart from its pharmacological relevance, is a demanding target for ATAs as the bridged bicyclic ring provides substantial steric challenges. Protein engineering combining rational design and directed evolution enabled the identification of an ATA variant which catalyzes the specific synthesis of the target exo-amine with >99.5% selectivity.

@article{C6OB02139E, abstract = {Application of amine transaminases (ATAs) for stereoselective amination of prochiral ketones represents an environmentally benign and economically attractive alternative to transition metal catalyzed asymmetric synthesis. However{,} the restrictive substrate scope has limited the conversion typically to non-sterically demanding scaffolds. Recently{,} we reported on the identification and design of fold class I ATAs that effect a highly selective asymmetric synthesis of a set of chiral aromatic bulky amines from the corresponding ketone precursors in high yield. However{,} for the specific amine synthetic approach extension targeted here{,} the selective formation of an exo- vs. endo-isomer{,} these biocatalysts required additional refinement. The chosen substrate (exo-3-amino-8-aza-bicyclo[3.2.1]oct-8-yl-phenyl-methanone){,} apart from its pharmacological relevance{,} is a demanding target for ATAs as the bridged bicyclic ring provides substantial steric challenges. Protein engineering combining rational design and directed evolution enabled the identification of an ATA variant which catalyzes the specific synthesis of the target exo-amine with >99.5% selectivity.}, added-at = {2016-11-04T11:06:30.000+0100}, author = {Weiß, M. S. and Pavlidis, I. V. and Spurr, P. and Hanlon, S. P. and Wirz, B. and Iding, H. and Bornscheuer, U. T.}, biburl = {https://www.bibsonomy.org/bibtex/295f97c73c53415c42bc2f9315a1518d7/biochemie}, description = {Protein-engineering of an amine transaminase for the stereoselective synthesis of a pharmaceutically relevant bicyclic amine - Organic & Biomolecular Chemistry (RSC Publishing)}, doi = {10.1039/C6OB02139E}, interhash = {82fc3d118f00bfee64e3d535bde33d11}, intrahash = {95f97c73c53415c42bc2f9315a1518d7}, journal = {Org. Biomol. Chem.}, keywords = {herberg myown}, number = 43, pages = {10249-10254}, publisher = {The Royal Society of Chemistry}, timestamp = {2016-11-04T11:06:30.000+0100}, title = {Protein-engineering of an amine transaminase for the stereoselective synthesis of a pharmaceutically relevant bicyclic amine}, url = {http://dx.doi.org/10.1039/C6OB02139E}, volume = 14, year = 2016 }