Amine Synthesis Using the Amine Donor N-Phenyl Putrescine and the Johnson Matthey Transaminase Biocatalyst Library : Smart amine donors facilitate production of amines at high percentage yields

Abstract

Chiral amines are important building blocks in the pharmaceutical, agrochemical and chemical industries. There is a drive to augment traditional transition metal catalysts with ‘green’ alternatives such as biocatalysts. Transaminase (TA) biocatalysts can be used in combination with ‘smart’ sacrificial amine donors to synthesise a variety of aliphatic and aromatic amines from the corresponding aldehydes and ketones. Despite their enormous potential, the unfavourable reaction equilibrium often limits the widespread application of TAs for industrial synthesis. Recently we disclosed a new biomimetic amine donor N-phenyl putrescine (NPP), which was inspired by the biosynthesis of the dipyrroloquinoline alkaloids. NPP was demonstrated to have good activity with a library of commercial and wild-type TAs (total 25 TAs). This work focused on exploring the use of NPP with the Johnson Matthey TA kit (17 biocatalysts; eight S-selective and nine R-selective) and three different amine acceptors (vanillin, benzaldehyde and acetophenone). NPP worked well with all 17 TAs and gave the corresponding amine products vanillylamine, benzylamine and methylbenzylamine (MBA) in up to 85% high-performance liquid chromatography (HPLC) yield. From the screen, STA-14 was identified as a good biocatalyst for further analysis and used in a comparative screen of NPP versus the commonly used donor iPrNH2. It was found that NPP was the best amine donor and used to prepare S-methylbenzylamine in >99.5% enantiomeric excess (e.e.). This work, combined with our previous study, highlights the potential of NPP in the biocatalytic synthesis of amines.