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

Abstract

AbstractBACKGROUNDAmine transaminases have been extensively used for synthesizing various pharmaceutically relevant compounds, mainly in aqueous media. However, their applications are often limited by poor substrate solubility, low productivity and difficult product separation. This paper reports the use of Jeffamine® ED‐600, a novel polyether amine donor, for the transaminase‐catalyzed synthesis of 4‐phenyl‐2‐butylamine in non‐aqueous media.RESULTSEnzymatic transamination was performed in the presence of a non‐polar organic solvent (n‐heptane), in which the selected amine donor is not soluble, thus a two‐liquid‐phase system was achieved. Coupling the reaction system with membrane‐assisted extraction resulted in simultaneous recovery of product, without any consistent contamination of the unreacted substrates. Moreover, a product yield of 60% was reached, compared with 15% without product extraction. The reaction was also successfully conducted without addition of any organic solvent, thus providing the first example of a solvent‐free transamination system. In the presence of only enzyme and substrates, up to 6‐fold higher product concentrations were achieved compared with the reaction performed in organic solvent.CONCLUSIONThe use of the Jeffamine® ED‐600 in non‐aqueous media resulted beneficial for 4‐phenyl‐2‐butylamine synthesis. Enzymatic transamination in organic solvent with membrane‐assisted product extraction enabled shifting of the equilibrium and selective product extraction. Solvent‐free transamination minimized the required volume of the reactor and minimized the environmental impact. Extension to other substrate/enzyme solvent‐free systems could open new possibilities and perspectives in transaminase‐catalyzed chiral amine synthesis. © 2019 Society of Chemical Industry