Development of an amine transaminase-lipase cascade for chiral amide synthesis under flow conditions

• Published in: Green chemistry : an international journal and green chemistry resource : GC 2023-07, Vol.25 (15), p.641-65
• Main Authors: Pintor, Antía, Mattey, Ashley P, Lavandera, Iván, Gotor-Fernández, Vicente, Volkov, Alexey
• Format: Article
• Language: English
• Subjects: Acylation; Continuous flow; Enzymes; Green chemistry; Ketones; Lipase; Optimization; Polymer coatings; Polymers; Porosity; Reactors; Reagents; Substrates; Transaminase; Transaminases
• ISSN: 1463-9262; 1463-9270
• DOI: 10.1039/d3gc02426a

The use of multienzymatic systems has gained increasing attention as a method of choice for complex (asymmetric) syntheses. Incompatibilities between substrates, reagents and/or enzymes in one-pot batch conditions can hamper the applicability of a pursued cascade, so the use of flow systems provide useful synthetic solutions. The implementation of immobilised enzymes in continuous flow reactors allows the compartmentalisation and segregation of the enzymes in separate reactors, leading to otherwise disfavoured reaction cascades. Here, an amine transaminase and a lipase have been immobilised on polymer-coated controlled porosity glass carrier materials and studied for the first time together in the transamination of a prochiral ketone followed by acylation of the corresponding chiral amine in flow mode, two incompatible transformations under batch. Thus, the preparation of ( R )- N -(1-phenoxypropan-2-yl)acetamide was accomplished after optimisation of the reaction conditions. An amine transaminase and a lipase have been immobilised in separated reactors containing EziG polymer-coated controlled porosity glass carrier materials to transform 1-phenoxypropan-2-one into the corresponding ( R )-acetamide in organic solvent.