A Rapid Selection Procedure for Simple Commercial Implementation of ω-Transaminase Reactions

Abstract

A stepwise selection procedure is presented to quickly evaluate whether a given ω-transaminase reaction is suitable for a so-called “simple” scale-up for fast industrial implementation. Here “simple” is defined as a system without the need for extensive process development or specialized equipment. The procedure may be used when investment in intensive process development cannot be justified or when rapid execution is paramount, for applications such as small singular batches. The three-step evaluation procedure consists of: (1) thermodynamic assessment, (2) biocatalyst activity screening, and (3) determination of product inhibition. The method is exemplified with experimental work focused on two products: 1-(4-bromophenyl)­ethylamine and (S)-(+)-3-amino-1-Boc-piperidine, synthesized from their corresponding pro-chiral ketones each with two alternative amine donors, propan-2-amine, and 1-phenylethylamine. Each step of the method has a threshold value, which must be surpassed to allow “simple” implementation, helping select suitable combinations of substrates, enzymes, and donors. One reaction pair, 1-Boc-3-piperidone with propan-2-amine, met the criteria of the three-step selection procedure and was subsequently run at 25 mL scale synthesizing (S)-(+)-3-amino-1-Boc-piperidine at concentrations up to 75 g/L. However, the highest product yield (70%) was obtained at a lower substrate concentration of 50 g/L.

Role of Biocatalysis in Sustainable Chemistry

“…Use of alternative substrates should be a better strategy to improve the reaction ΔG value. 412 These are important research targets for the future to ensure that the sustainable benefits of biocatalysis are fully exploited. This will enable still further the implementation of biocatalytic syntheses across all industries.…”

Development of Biotransamination Reactions towards the 3,4-Dihydro-2H-1,5-benzoxathiepin-3-amine Enantiomers

“…In this context, the synthesis of chiral amines is particularly challenging, with the conversion of prochiral ketones into optically active amines receiving great attention in recent years [11][12][13][14] by using mainly imine reductases [15][16][17] and amine transaminases (ATAs) [18][19][20][21][22][23]. Taking into account the potential of ATAs in the single biotransamination of cyclic ketones [24][25][26][27][28][29][30][31][32], even as part of multienzymatic sequences [33][34][35][36][37][38], but especially since they have served as valuable biocatalysts in the production of pharmacologically active products [39][40][41][42][43], we have focused herein our efforts in the pursuit of an efficient biotransamination protocol for 3,4-dihydro-2H-1,5-benzoxathiepin-3-one (6).…”

Jeffamine® ED‐600: a polyether amine donor for enzymatic transamination in organic solvent/solvent‐free medium with membrane‐assisted product extraction

“…The synthetic potential of amine transaminases (ATAs) for the synthesis of chiral amines is enormous, especially when the transamination is carried out in the asymmetric synthesis mode . Although research in both academia and industry has been extensively performed, general challenges including substrate/product inhibition, instability of the enzyme and unfavorable thermodynamic equilibrium need to be overcome. Such limitations imply that the process parameters (substrate concentration, biocatalyst performance and product yield, productivity) of ATA‐catalyzed processes are not completely industrially competitive yet, despite a few successful industrial applications …”