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Development of an amine transaminase-lipase cascade for chiral amide synthesis under flow conditions†
Ashley P. Mattey,Iván Lavandera,Vicente Gotor-Fernández,Alexey Volkov
Green Chemistry Pub Date : 07/19/2023 00:00:00 , DOI:10.1039/D3GC02426A
Abstract

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.

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