Premium
Combination of the Suzuki–Miyaura Cross‐Coupling Reaction with Engineered Transaminases
Author(s) -
Dawood Ayad W. H.,
Bassut Jonathan,
de Souza Rodrigo O. M. A.,
Bornscheuer Uwe T.
Publication year - 2018
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201804366
Subject(s) - transamination , chemistry , biocatalysis , amine gas treating , combinatorial chemistry , reaction conditions , cascade reaction , coupling reaction , cascade , organic chemistry , catalysis , enzyme , reaction mechanism , chromatography
The combination of enzymatic and chemical reaction steps is one important area of research in organic synthesis, preferentially as cascade reactions in one‐pot to improve total conversion and achieve high operational stability. Here, the combination of the Suzuki–Miyaura reaction is described to synthesize biaryl compounds followed by a transamination reaction. Careful optimization of the reaction conditions required for the chemo‐ and biocatalysis reaction enabled an efficient two‐step‐one‐pot reaction yielding the final chiral amines with excellent optical purity (>99 % ee ) in up to 84 % total conversion. Key to the success was the protein engineering of the amine transaminases from Asperguillus fumigatus (4CHI‐TA) where single alanine mutations increased the conversion up to 2.3‐fold. Finally, the transfer to a continuous flow system after immobilization of the best 4CHI‐TA variant is demonstrated.