Realizing the Continuous Chemoenzymatic Synthesis of Anilines Using an Immobilized Nitroreductase

Immobilizationof a nitroreductase enzyme permits continuouschemoenzymatic synthesis of anilines. The use of biocatalysisfor classically synthetic transformationshas seen an increase in recent years, driven by the sustainabilitycredentials bio-based approaches can offer the chemical industry.Despite this, the biocatalytic reduction of aromatic nitro compoundsusing nitroreductase biocatalysts has not received significant attentionin the context of synthetic chemistry. Herein, a nitroreductase (NR-55)is demonstrated to complete aromatic nitro reduction in a continuouspacked-bed reactor for the first time. Immobilization on an amino-functionalizedresin with a glucose dehydrogenase (GDH-101) permits extended reuseof the immobilized system, all operating at room temperature and pressurein aqueous buffer. By transferring into flow, a continuous extractionmodule is incorporated, allowing the reaction and workup to be continuouslyundertaken in a single operation. This is extended to showcase a closed-loopaqueous phase, permitting reuse of the contained cofactors, with aproductivity of >10 g(product) g(NR-55) (-1) and milligram isolated yields >50% for theproductanilines. This facile method removes the need for high-pressure hydrogengas and precious-metal catalysts and proceeds with high chemoselectivityin the presence of hydrogenation-labile halides. Application of thiscontinuous biocatalytic methodology to panels of aryl nitro compoundscould offer a sustainable approach to its energy and resource-intensiveprecious-metal-catalyzed counterpart.

Automated summary

The immobilization of nitroreductase enzyme enables continuous chemoenzymatic synthesis of anilines. The application of biocatalysis in classical synthetic transformations has gained attention due to the sustainability benefits it offers to the chemical industry. However, the biocatalytic reduction of aromatic nitro compounds using nitroreductase biocatalysts has not been extensively explored in synthetic chemistry. This study demonstrates the successful reduction of aromatic nitro compounds using immobilized nitroreductase in a continuous packed-bed reactor, allowing for extended reuse of the immobilized system.