Realizing the Continuous Chemoenzymatic Synthesis of Anilines Using an Immobilized Nitroreductase

Cosgrove, Sebastian C.; Miller, Gavin J.; Bornadel, Amin; Dominguez, Beatriz

Abstract

The use of biocatalysis for classically synthetic transformations has seen an increase in recent years, driven by the sustainability credentials bio-based approaches can offer the chemical industry. Despite this, the biocatalytic reduction of aromatic nitro compounds using nitroreductase biocatalysts has not received significant attention in the context of synthetic chemistry. Herein, a nitroreductase (NR-55) is demonstrated to complete aromatic nitro reduction in a continuous packed-bed reactor for the first time. Immobilization on an amino-functionalized resin with a glucose dehydrogenase (GDH-101) permits extended reuse of the immobilized system, all operating at room temperature and pressure in aqueous buffer. By transferring into flow, a continuous extraction module is incorporated, allowing the reaction and workup to be continuously undertaken in a single operation. This is extended to showcase a closed-loop aqueous phase, permitting reuse of the contained cofactors, with a productivity of >10 g g and milligram isolated yields >50% for the product anilines. This facile method removes the need for high-pressure hydrogen gas and precious-metal catalysts and proceeds with high chemoselectivity in the presence of hydrogenation-labile halides. Application of this continuous biocatalytic methodology to panels of aryl nitro compounds could offer a sustainable approach to its energy and resource-intensive precious-metal-catalyzed counterpart. [Abstract copyright: © 2023 The Authors. Published by American Chemical Society.]

Citation

Cosgrove, S. C., Miller, G. J., Bornadel, A., & Dominguez, B. (2023). Realizing the Continuous Chemoenzymatic Synthesis of Anilines Using an Immobilized Nitroreductase. ACS sustainable chemistry & engineering, 11(23), 8556-8561. https://doi.org/10.1021/acssuschemeng.3c01204

• Journal Article Type: Article
• Acceptance Date: Jun 2, 2023
• Online Publication Date: Jun 2, 2023
• Publication Date: Jun 1, 2023
• Deposit Date: Jun 12, 2023
• Publicly Available Date: Jun 12, 2023
• Journal: ACS Sustainable Chemistry & Engineering
• Electronic ISSN: 2168-0485
• Publisher: American Chemical Society
• Peer Reviewed: Peer Reviewed
• Volume: 11
• Issue: 23
• Pages: 8556-8561
• DOI: https://doi.org/10.1021/acssuschemeng.3c01204
• Keywords: Renewable Energy, Sustainability and the Environment; General Chemical Engineering; Environmental Chemistry; General Chemistry