Hydrogen‐Borrowing Alcohol Bioamination with Coimmobilized Dehydrogenases

Abstract

The amination of alcohols is an important transformation in chemistry. The redox-neutral (i.e., hydrogen-borrowing) asymmetric amination of alcohols is enabled by the combination of an alcohol dehydrogenase (ADH) with an amine dehydrogenase (AmDH). In this work, we enhanced the efficiency of hydrogen-borrowing biocatalytic amination by co-immobilizing both dehydrogenases on controlled porosity glass FeIII ion-affinity beads. The recyclability of the dual-enzyme system was demonstrated (5 cycles) with total turnover numbers of >4000 and >1000 for ADH and AmDH, respectively. A set of (S)-configured alcohol substrates was aminated with up to 95% conversion and >99%ee (R). Preparative-scale amination of (S)-phenylpropan-2-ol resulted in 90% conversion and 80% yield of the product in 24 h.

Sequential Two‐Step Stereoselective Amination of Allylic Alcohols through the Combination of Laccases and Amine Transaminases

“…Biocatalytic methods have emerged as a sustainable solution for the synthesis of chiral amines by means of the single action of enzymes of several classes, including lipases, amine transaminases (ATAs), amine oxidases, amine dehydrogenases, imine reductases or reductive aminases, but, interestingly, great efforts have in recent years been devoted to the synthesis of chiral amines through chemo‐, photo‐ and multienzymatic approaches . As an example, the selective amination of racemic sec ‐alcohols through elegant cascades based on the combination of alcohol‐dehydrogenase‐catalysed oxidation to ketones with subsequent bioamination by using ATAs or amine dehydrogenases has been described. In spite of these efforts, the biocatalytic synthesis of (3 E )‐4‐arylbut‐3‐en‐2‐amines has received little attention, the activity of commercially available amine transaminases for the bio‐transamination of (3 E )‐4‐phenylbut‐3‐en‐2‐one into optically active (3 E )‐4‐phenylbut‐3‐en‐2‐amine being low (<30 %) …”

Mechanistic Insight into the Catalytic Promiscuity of Amine Dehydrogenases: Asymmetric Synthesis of Secondary and Primary Amines

“…On the other hand, our research group and other groups have shown that a large excess of a (ca. 0.2–1 m ) is required to drive the reductive amination of ketone substrates (15–50 m m ) in aqueous buffer to a significant extent . Moreover, AmDHs, such as Ch1‐AmDH, have a K M value of about 1 m for a .…”

Broadening the Scope of Biocatalysis in Sustainable Organic Synthesis

“…This is not a simple matter, as most ADHs are highly enantioselective. More recently, the efficiency of the direct asymmetric amination of a secondary alcohol was improved by co‐immobilization of the ADH and AmDH …”