Single-Electron Oxidation-Initiated Enantioselective Hydrosulfonylation of Olefins Enabled by Photoenzymatic Catalysis

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(4), P. 2748 - 2756

Published: Jan. 12, 2024

Controlling the enantioselectivity of hydrogen atom transfer (HAT) reactions has been a long-standing synthetic challenge. While recent advances on photoenzymatic catalysis have demonstrated great potential non-natural photoenzymes, all transformations are initiated by single-electron reduction substrate, with only one notable exception. Herein, we report an oxidation-initiated enantioselective hydrosulfonylation olefins using novel mutant gluconobacter ene-reductase (GluER-W100F-W342F). Compared to known systems, our approach does not rely formation electron donor–acceptor complex between substrates and enzyme cofactor simplifies reaction system obviating addition regeneration mixture. More importantly, GluER variant exhibits high reactivity broad substrate scope. Mechanistic studies support proposed mechanism reveal that tyrosine-mediated HAT process is involved.

Language: Английский

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From Ground-State to Excited-State Activation Modes: Flavin-Dependent “Ene”-Reductases Catalyzed Non-natural Radical Reactions

Accounts of Chemical Research, Journal Year: 2024, Volume and Issue: 57(9), P. 1446 - 1457

Published: April 11, 2024

ConspectusEnzymes are desired catalysts for chemical synthesis, because they can be engineered to provide unparalleled levels of efficiency and selectivity. Yet, despite the astonishing array reactions catalyzed by natural enzymes, many reactivity patterns found in small molecule have no counterpart living world. With a detailed understanding mechanisms utilized catalysts, we identify existing enzymes with potential catalyze that currently unknown nature. Over past eight years, our group has demonstrated flavin-dependent "ene"-reductases (EREDs) various radical-mediated selectivity, solving long-standing challenges asymmetric synthesis.This Account presents development EREDs as general radical reactions. While developed multiple generating radicals within protein active sites, this account will focus on examples where flavin mononucleotide hydroquinone (FMNhq) serves an electron transfer initiator. initial mechanistic hypotheses were rooted electron-transfer-based initiation commonly used synthetic organic chemists, ultimately uncovered emergent unique site. We begin covering intramolecular discussing how activates substrate reduction altering redox-potential alkyl halides templating charge complex between flavin-cofactor. Protein engineering been modify fundamental photophysics these reactions, highlighting opportunity tune systems further using directed evolution. This section highlights range coupling partners termination available reactions.The next intermolecular role enzyme-templated ternary complexes among cofactor, halide, partner gating ensure it only occurs when both substrates bound highlight applications activation mode, including olefin hydroalkylation, carbohydroxylation, arene functionalization, nitronate alkylation. also discusses favor steps elusive solution reductive nitroalkanes. aware several recent EREDs-catalyzed photoenzymatic transformations from other groups. discuss results papers context nuances substrates.These biocatalytic often complement state-of-the-art small-molecule-catalyzed making valuable addition chemist's toolbox. Moreover, underlying principles studied potentially operative cofactor-dependent proteins, opening door different types enzyme-catalyzed anticipate serve guide inspire broad interest repurposing access new transformations.

Language: Английский

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Photobiocatalysis: A promising tool for sustainable synthesis

Chem Catalysis, Journal Year: 2024, Volume and Issue: 4(7), P. 100933 - 100933

Published: Feb. 29, 2024

Language: Английский

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A Type of Chiral C₂-Symmetric Arylthiol Catalyst for Highly Enantioselective Anti-Markovnikov Hydroamination

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(23), P. 16248 - 16256

Published: May 29, 2024

The development of chiral hydrogen donor catalysts is fundamental in the expansion and innovation asymmetric organocatalyzed reactions via an enantioselective atom transfer (HAT) process. Herein, unprecedented type C2-symmetric arylthiol derived from readily available enantiomeric lactate ester was developed. With these catalysts, anti-Markovnikov alkene hydroamination–cyclization reaction established, affording a variety pharmaceutically interesting 3-substituted piperidines with moderate to high enantioselectivity. Results designed control experiments theoretical computation rationalized origin stereocontrol disclosed spatial effect moiety thiols on We believed facile synthesis, flexible tunability, effective enantioselectivity-controlling capability would shed light versatile HAT related reactions.

Language: Английский

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Enantioselective biosynthesis of vicinal diamines enabled by synergistic photo/biocatalysis consisting of an ene-reductase and a green-light-excited organic dye

CHINESE JOURNAL OF CATALYSIS (CHINESE VERSION), Journal Year: 2025, Volume and Issue: 68, P. 223 - 229

Published: Jan. 1, 2025

Language: Английский

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Mechanistic investigation of repurposed photoenzymes with new-to-nature reactivity

Current Opinion in Green and Sustainable Chemistry, Journal Year: 2025, Volume and Issue: 52, P. 101009 - 101009

Published: Feb. 27, 2025

Language: Английский

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Bridging chemistry and biology for light-driven new-to-nature enantioselective photoenzymatic catalysis

Chemical Society Reviews, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Merging enzymes with light-driven photocatalysis has given rise to the burgeoning field of photoenzymatic catalysis.

Language: Английский

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Engineering catalytically promiscuous enzymes to serve new functions

Biotechnology Advances, Journal Year: 2025, Volume and Issue: unknown, P. 108601 - 108601

Published: May 1, 2025

Language: Английский

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Reduction of Tertiary Carbon Radicals via Asymmetric Hydrogen Atom Transfer (AHAT)^†

Chinese Journal of Chemistry, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 18, 2024

Comprehensive Summary In the past two decades, development of asymmetric radical reactions has achieved tremendous progress, which emerged as a powerful tool for synthesis chiral molecules in synthetic chemistry. Among diverse array processes, transfer hydrogen atoms to tertiary carbon radicals offers potential constructing centers stereoselective fashion. Notwithstanding challenges associated with reactive and evanescent nature species, use reagents or mediators enabled stereocontrol atom ( AHAT ), provides novel avenues advancing field synthesis. Key Scientists

Language: Английский

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Chiral Sulfones via Single-Electron Oxidation-Initiated Photoenzymatic Catalysis

Synlett, Journal Year: 2024, Volume and Issue: unknown

Published: June 18, 2024

Abstract We recently achieved an oxidation-initiated photoenzymatic enantioselective hydrosulfonylation of olefins through the utilization a new Gluconobacter ene-reductase mutant (GluER-W100F-W342F). Our method simplifies reaction system by eliminating need for cofactor regeneration mixture and, in contrast with previous systems, does not depend on formation electron donor–acceptor (EDA) complex between substrates and enzyme cofactor. Moreover, GluER variant exhibits good substrate compatibility excellent enantioselectivity. Mechanistic investigations indicate that tyrosine-mediated HAT process is involved support proposed mechanism. In this Synpacts article, we discuss conceptual framework led to discovery reflect key aspects its development. 1 Introduction 2 Conceptual Background 2.1 Intramolecular Photoenzymatic Reactions via Single-Electron Reduction 2.2 Intermolecular 3 The Development Process 4 Conclusion

Language: Английский

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