Membrane contactor for effective chiral amine synthesis separation

Article published on 13 August 2019 Anita Buekenhoudt

Chiral amines are key building blocks for many new pharmaceuticals (APIs). The bulk of medicines currently produced are made of chiral compounds.

In origin, most chiral compounds are available as mixtures of two equimolar enantiomers (molecules that are mirror images of one another); exhibiting marked differences in activities (e.g. toxicology, pharmacology,) while being structurally the same. The functional difference of the enantiomers  determines their usability in medical, agrochemical and chemical product synthesis and that's why their separation is of great added value. The application of chiral preparations has a much higher success rate if the unwanted enantiomer is not present.

Enantiomeric separation is a challenge as it requires advanced verification to confirm the desired product. An enzymatic approach, however, using transaminase, appears to lead to successfully controlled asymmetric production of chiral amines. But despite the advantages of high selectivity, the transamination reaction is a reversible reaction, often with an unfavourable thermodynamic equilibrium which limits obtaining high chiral amine yields.

VITO solution

An enzymatic transamination process that allows for synthesis and separation of chiral amines at an industrial scale.

An innovative membrane contactor setup allows for a transaminase catalysed reaction between a donor amine and acceptor ketone in combination with a hydrophobic membrane based separation of the produced chiral amine. This way, a large scale chiral amine synthesis, separation and enrichment is achievable.

The process allows obtaining chiral amines in high yield. The hydrophobic membrane based separation allows the selective removal of the desired chiral amine from the reaction mixture. This removal influences the reaction equilibrium of the transaminase reaction in the remaining reaction mixture. The removal of the chiral amine limits product inhibition of the transaminase reaction, allowing the transamination reaction to be performed with lower solvent load and improved process mass intensity (PMI).

 

 

Anita Buekenhoudt Anita Buekenhoudt
About the author

Research & Development expert with extensive expertise in membrane filtration in a wide range of industrial applications. Specific focus on the potential and applicability of porous and dense ceramic membranes. Co-inventor of different membrane-based chemical processes for process intensification, and innovative functionalisation of ceramic membranes for affinity-based separations.

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