AI Article Synopsis
- - Flavin-dependent 'ene'-reductases (EREDs) are specialized enzymes that typically reduce specific alkenes like enones and nitroalkenes, but their catalytic activity is limited by their native mechanism.
- - Recent research shows that under visible light and with a photoredox catalyst, EREDs can also reduce vinyl pyridines through a radical mechanism, transforming them into stable benzylic radicals.
- - Computational studies indicate that these benzylic radicals are "dynamically stable," meaning they last long enough to enter the enzyme's active site, allowing for targeted, stereoselective hydrogen transfer, thus broadening the practical applications of EREDs.
Article Abstract
Flavin-dependent 'ene'-reductases (EREDs) are highly selective catalysts for the asymmetric reduction of activated alkenes. This function is, however, limited to enones, enoates, and nitroalkenes using the native hydride transfer mechanism. Here we demonstrate that EREDs can reduce vinyl pyridines when irradiated with visible light in the presence of a photoredox catalyst. Experimental evidence suggests the reaction proceeds via a radical mechanism where the vinyl pyridine is reduced to the corresponding neutral benzylic radical in solution. DFT calculations reveal this radical to be "dynamically stable", suggesting it is sufficiently long-lived to diffuse into the enzyme active site for stereoselective hydrogen atom transfer. This reduction mechanism is distinct from the native one, highlighting the opportunity to expand the synthetic capabilities of existing enzyme platforms by exploiting new mechanistic models.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1002/anie.202003125 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Turning the band alignment of carbon dots for visible-light-driven enzymatic asymmetric reduction of aromatic ketone.
Int J Biol Macromol
January 2025
Key Laboratory of Organosilicon Chemistry and Materials Technology, Ministry of Education; College of Materials Chemistry and Chemical Engineering, Hangzhou Normal University, Hangzhou, Zhejiang 311121, China. Electronic address:
Keto reductases are crucial NAD(P)H-dependent enzymes used for the enantioselective synthesis of alcohols from prochiral ketones. Typically, the NADPH cofactor is regenerated through a second enzyme and/or substrate. However, photocatalytic cofactor regeneration using water as a sacrificial electron and hydrogen donor presents a promising alternative, albeit a challenging one.
View Article and Find Full Text PDFAsymmetric photoenzymatic incorporation of fluorinated motifs into olefins.
Science
July 2024
DOE Center for Advanced Bioenergy and Bioproducts Innovation, University of Illinois Urbana-Champaign, Urbana, IL 61801, USA.
Enzymes capable of assimilating fluorinated feedstocks are scarce. This situation poses a challenge for the biosynthesis of fluorinated compounds used in pharmaceuticals, agrochemicals, and materials. We developed a photoenzymatic hydrofluoroalkylation that integrates fluorinated motifs into olefins.
View Article and Find Full Text PDFExploiting Nitroreductases for the Tailored Photoenzymatic Synthesis of Structurally Diverse Heterocyclic Compounds.
Chemistry
October 2024
Department of Chemical and Pharmaceutical Biology, Groningen Research Institute of Pharmacy, University of Groningen, Antonius Deusinglaan 1, 9713 AV, Groningen, The Netherlands.
N-heterocyclic compounds have a broad range of applications and their selective synthesis is very appealing for the pharmaceutical and agrochemical industries. Herein we report the usage of the flavin-dependent nitroreductase BaNTR1 for the photoenzymatic synthesis of various anthranils and quinolines from retro-synthetically designed o-nitrophenyl-substituted carbonyl substrates, achieving high conversions (up to >99 %) and good product yields (up to 96 %). Whereas the effective production of anthranils required the inclusion of HO in the reaction mixtures to accumulate the needed hydroxylamine intermediates, the formation of quinolines required the use of anaerobic or reducing conditions to efficiently generate the essential amine intermediates.
View Article and Find Full Text PDFPhotoenzymatic Asymmetric Hydroamination for Chiral Alkyl Amine Synthesis.
J Am Chem Soc
April 2024
DOE Center for Advanced Bioenergy and Bioproducts Innovation, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, United States.
Chiral alkyl amines are common structural motifs in pharmaceuticals, natural products, synthetic intermediates, and bioactive molecules. An attractive method to prepare these molecules is the asymmetric radical hydroamination; however, this approach has not been explored with dialkyl amine-derived nitrogen-centered radicals since designing a catalytic system to generate the aminium radical cation, to suppress deleterious side reactions such as α-deprotonation and H atom abstraction, and to facilitate enantioselective hydrogen atom transfer is a formidable task. Herein, we describe the application of photoenzymatic catalysis to generate and harness the aminium radical cation for asymmetric intermolecular hydroamination.
View Article and Find Full Text PDFCovalent Organic Frameworks Based Photoenzymatic Nano-reactor for Asymmetric Dynamic Kinetic Resolution of Secondary Amines.
Angew Chem Int Ed Engl
April 2024
College of Chemistry, Huazhong Agricultural University, Wuhan, 430070, P. R. China.
Bio-catalysis represents a highly efficient and stereoselective method for the synthesis of valuable chiral compounds, however, the poor stability and limited reaction types of free enzymes restrict their wide application in industrial production. In this work, to overcome these problems, a multifunctional photoenzymatic nanoreactor CALB@COF-Ir was developed through the encapsulation of Candida antarctica lipase B (CALB) in a photosensitive covalent organic framework COF-Ir. This bio-nanocluster serves as efficient catalysts in asymmetric dynamic kinetic resolution (DKR) of secondary amines to give a series of chiral amines in high yields (up to 99 %) and enantioselectivities (up to 99 % ee).
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!