Stereoselective amination of racemic sec-alcohols through sequential application of laccases and transaminases

Abstract

A one-pot/two-step chemoenzymatic sequential methodology has been developed for the selective amination of secondary alcohols by combining the laccase from Trametes versicolor/TEMPO catalytic system with the stereoselective action of transaminases.

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

“…Interestingly, only 7 % conversion into the ketone 2 a was observed in the case of a high TEMPO concentration (33 mol %, entry 1) in the buffer system. Therefore, to favour the solubility of the substrate, tert ‐butyl methyl ether (MTBE) was employed as organic cosolvent (20–50 %, v / v , entries 2–5). Because of the low boiling point of MTBE it had evaporated from the medium after the first 3 hours, leading to a monophasic system, and complete conversion was attained when 50 % ( v / v ) MTBE and 33 mol % TEMPO were employed (entry 3), although the use of lower TEMPO loadings did not allow the reaction to reach completion (entries 4 and 5) even with the use of prolonged times and either 20 mol % TEMPO (94 and 98 % conversion after 24 and 48 h, respectively) or 10 mol % TEMPO (70 and 74 % after 24 and 48 h, respectively).…”

“…However, if the oxidation of natural substrates is attempted, these enzymes require the use of a chemical mediator such as the 2,2,6,6‐tetramethylpiperidinoxyl (TEMPO) radical . The oxidation of diols, amino alcohols, profenols and benzylic and allylic alcohols in this manner has been fully exploited in our research group, with the development of sequential multienzymatic transformations through judicious modification of the reaction medium having in some cases been possible. These chemoenzymatic strategies have included dynamic kinetic resolutions and deracemisation of alcohols in combination with alcohol dehydrogenases, the selective amination of benzylic alcohols by use of amine transaminases, or the redox isomerisation of allylic alcohols by coupling the action of laccases with that of ene‐reductases …”

Extending Designed Linear Biocatalytic Cascades for Organic Synthesis

“…One reason is different pH optima, another reason is the reagent for the second step (2‐propyamine), which would be oxidized by the enzyme of the first step. Therefore, this asymmetric amination of secondary alcohols was based on a sequential process involving the use of a laccase from Trametes versicolor /TEMPO catalytic system for the non‐stereoselective oxidation of alcohols to the corresponding ketones, followed by stereoselective amination to the corresponding amines by transaminases (Scheme ) . Under optimized reaction conditions, racemic substituted (hetero)aromatic sec ‐alcohols were converted into amines with good to excellent optical purity (90–99 % ee ) and conversions ranging from 67 to 99 %.…”

Two‐Enzyme Hydrogen‐Borrowing Amination of Alcohols Enabled by a Cofactor‐Switched Alcohol Dehydrogenase

“…The biocatalytic amination of alcohols through enzyme cascades by employing ω‐transaminases has been reported, although these systems typically require several equivalents of a sacrificial amine donor to drive the reactions to high conversions . A recent report by Lavandera and co‐workers described the use of stoichiometric diamines as amine donors in an efficient laccase/2,2,6,6‐tetramethylpiperidin‐1‐oxyl (TEMPO) coupled reaction for the amination of alcohols …”