Katharina Tauber

ω-Transaminases for the synthesis of non-racemic α-chiral primary amines

Optically pure amines are highly valuable products or key intermediates for a vast number of bioactive compounds; however, efficient methods for their preparation are rare. omega-Transaminases (TAs) can be applied either for the kinetic resolution of racemic amines or for the asymmetric synthesis of amines from the corresponding ketones. The latter process is more advantageous because it leads to 100% product, and is therefore a major focus of this review. This review summarizes various methodologies for transamination reactions, and provides an overview of omega-TAs that have the potential to be used for the preparation of a broad spectrum of alpha-chiral amines. Recent methodological developments as well as some recently identified novel omega-TAs warrant an update on this topic.

Redox Self-Sufficient Biocatalyst Network for the Amination of Primary Alcohols†

Driving the machinery: A biocatalytic redox-neutral cascade for the preparation of terminal primary amines from primary alcohols at the expense of ammonia has been established in a one-pot one-step method. Applying this artificial biocatalyst network, long-chain 1,ω-alkanediols were converted into diamines, which are building blocks for polymers, in up to 99 % conversion.

Artificial Multi‐Enzyme Networks for the Asymmetric Amination of sec‐Alcohols

Various artificial network designs that involve biocatalysts were tested for the asymmetric amination of sec-alcohols to the corresponding α-chiral primary amines. The artificial systems tested involved three to five redox enzymes and were exemplary of a range of different sec-alcohol substrates. Alcohols were oxidised to the corresponding ketone by an alcohol dehydrogenase. The ketones were subsequently aminated by employing a ω-transaminase. Of special interest were redox-neutral designs in which the hydride abstracted in the oxidation step was reused in the amination step of the cascade. Under optimised conditions up to 91 % conversion of an alcohol to the amine was achieved.

Amination of benzylic and cinnamic alcohols via a biocatalytic, aerobic, oxidation–transamination cascade

The amination of benzylic and cinnamic alcohols was achieved via a biocatalytic, one-pot oxidation–transamination cascade in aqueous medium at physiological conditions. Alcohol oxidation by galactose oxidase at the expense of O2 furnished the corresponding aldehydes, which were aminated using ω-transaminases in situ. The applicability of this method was demonstrated by a short synthesis of the antifungal agent naftifine.

A highly efficient ADH‐coupled NADH‐recycling system for the asymmetric bioreduction of carbon‐carbon double bonds using enoate reductases

The asymmetric bioreduction of activated alkenes catalyzed by flavin-dependent enoate reductases from the OYE-family represents a powerful method for the production of optically active compounds. For its preparative-scale application, efficient and economic NADH-recycling is crucial. A novel enzyme-coupled NADH-recycling system is proposed based on the concurrent oxidation of a sacrificial sec-alcohol catalyzed by an alcohol dehydrogenase (ADH-A). Due to the highly favorable position of the equilibrium of ene-reduction versus alcohol-oxidation, the cosubstrate is only required in slight excess.

Creating a Biocatalyst for the Production of an Optically Pure Sterically Hindered Amine

The preparation of optically pure amines is one of the current hot topics in asymmetric synthesis employing chemical methods or biocatalytic approaches. 3] The original route for the preparation of sitagliptin 1, a drug needed for the treatment of diabetes mellitus type 2, encompassed a metal-catalyzed asymmetric reduction of an enamine by a rhodium catalyst (Scheme 1). The metal-catalyzed asymmetric hydrogenation

Aerobic oxidation of isosorbide and isomannide employing TEMPO/laccase

The oxidation of the renewable diols isosorbide and isomannide was successfully achieved using a TEMPO/laccase system. Furthermore, various TEMPO-derivatives were tested leading to conversions of up to >99% for the oxidation of isosorbide, isomannide, indanol and a halohydrin to the corresponding ketone.