Combination of the Suzuki-Miyaura Cross-Coupling Reaction with Engineered Transaminases

Chemistry : a European Journal
Ayad W H DawoodUwe T Bornscheuer

Abstract

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.

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Citations

Mar 18, 2020·Current Opinion in Chemical Biology·Xiaoqiang HuangHuimin Zhao
May 25, 2021·Chemical Society Reviews·Roger A SheldonDean Brady
Sep 17, 2019·The Journal of Organic Chemistry·Zahra Bazyar, Mona Hosseini-Sarvari

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