Application of Transaminases in a Disperse System for the Bioamination of Hydrophobic Substrates

Andrea Fiorati,Maria S Humble,Davide Tessaro,Per Berglund

doi:10.1002/adsc.201901434

Abstract

AbstractThe challenging bioamination of hydrophobic substrates has been attained through the employment of a disperse system consisting of a combination of a low polarity solvent (e. g. isooctane or methyl‐tert‐butylether), a non‐ionic surfactant and a minimal amount of water. In these conditions, amine transaminases (ATA) were shown to efficiently carry out the reductive amination of variously substituted cyclohexanones, providing good conversions often coupled with a superior stereoselectivity if compared with the corresponding chemical reductive amination. An array of synthetically useful 4‐substituted aminocyclohexanes was consequentially synthesized through biocatalysis, analyzed and stereochemically characterized.magnified image

Highlights

4-Substituted cyclohexylamines are important building blocks in medicinal chemistry.[1]
The key factor of this work is the activity of water in the organic medium; this is in line with the generally accepted mechanism of transamination,[7] where a water molecule is involved in the catalytic cycle
At first, following the procedure described by Chen et al.,[10] Cv-amine transaminases (ATA) was employed as a surfactant-stabilized powder in dry isooctane at 37 °C using 4-tertbutyl-cyclohexanone (1 a) as a model substrate (Scheme 2)

Summary

Introduction

4-Substituted cyclohexylamines are important building blocks in medicinal chemistry.[1]. The ATA from Chromobacterium violaceum (Cv-ATA) was applied as a suspension of surfactant-stabilized lyophilized powder for the stereoselective conversion of methoxyacetone to the corresponding amine in dry isooctane employing (S)-phenylethylamine ((S)-PEA) as amino donor (Scheme 2).[10] this approach led to unsatisfactory results when applied to 4substituted-cyclohexanones, in particular in terms of reaction rate. An aqueous solution of the enzyme, a non-ionic surfactant, the substrate, and an appropriate organic solvent are mixed to form a macroscopically homogeneous system.

Results

Conclusion