Implementation and scale-up of a semi-continuous transaminase-catalyzed reactive crystallization for the preparation of (S)-(3-methoxyphenyl)ethylamine

Crystallization-based downstream processing of ω-transaminase- and amine dehydrogenase-catalyzed reactions

“…The product itself can easily be recovered from the obtained product salt as described by Neuburger et al 54 While demonstrating a high efficiency, this method also allows for almost full recycling of the applied carboxylic acid through simple acidification, including its non-precipitated excesses for subsequent crystallizations.…”

“…Noteworthy, a direct combination of asymmetric biocatalytic synthesis and crystallization is present within the concept of in situ product crystallization (ISPC), otherwise known as reactive crystallization, and has proven to be effective in transaminase-catalyzed reactions. 27,50–54…”

“…Noteworthy, a direct combination of asymmetric biocatalytic synthesis and crystallization is present within the concept of in situ product crystallization (ISPC), otherwise known as reactive crystallization, and has proven to be effective in transaminase-catalyzed reactions. 27,[50][51][52][53][54] However, ISPC may encounter challenges, such as enzyme inhibition by the applied counterion or mechanical challenges (e.g. stirring).…”

Continuous flow-mode synthesis of (chiral) amines with transaminase: a strategic biocatalytic approach to essential building blocks

“…[135][136][137][138] Noteworthily, as previously mentioned, researchers from von Langermann group implemented an in situ product crystallization (ISPC) assisted by co-product (acetone) evaporation to perform the synthesis of S-methylbenzylamine derivatives, such as S-(3methoxyphenyl)ethylamine (S-MEA). 103,139 Such an elegant strategy relied on the use of crystallization agent (i.e. bulky carboxylic acid such as 3-diphenylpropionic acid) able to form poorly soluble crystalline salts with S-MEA, hereby driving the transamination equilibrium.…”

A Techno-economic Assessment of a Biocatalytic Chiral Amine Production Process Integrated with In Situ Membrane Extraction

“…Higher conversions of metaraminol were achieved when l -alanine was used as the amine donor. , Moreover, in situ product crystallization (ISPC) was proposed for an amine transaminase (ATA)-catalyzed reaction to shift the reaction equilibrium toward the products . Isopropylammonium 3,3-diphenylpropionate was used as the donor salt in an ATA reaction reported by von Langermann’s group (2018, 2019, 2021). − A barely soluble salt was formed with the product amine to overcome the thermodynamic limit. They further described a semicontinuous reaction approach with ISPC to obtain a product concentration of 1.2 mol/L.…”