Photoenzymatic Hydrosulfonylation for the Stereoselective Synthesis of Chiral Sulfones DOI
Xiaoyang Chen,

Dannan Zheng,

Linye Jiang

et al.

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(23)

Published: April 5, 2023

Abstract Chiral sulfones are recurrent motifs in pharmaceuticals and bioactive molecules. Although chemical methods have been developed to afford α‐ or β‐ chiral sulfones, these protocols rely heavily on the pre‐synthesis of structurally complicated starting materials metal complexes. Herein, we described a photoenzymatic approach for radical‐mediated stereoselective hydrosulfonylation. Engineered variants ene reductases provide efficient biocatalysts this transformation, enabling achieve series β‐chiral sulfonyl compounds with high yields (up 92 %) excellent e.r. values 99 : 1).

Language: Английский

Recent Advances in Employing Catalytic Donors and Acceptors in Electron Donor–Acceptor Complex Photochemistry DOI
Tarannum Tasnim, Mayokun J. Ayodele, Spencer P. Pitre

et al.

The Journal of Organic Chemistry, Journal Year: 2022, Volume and Issue: 87(16), P. 10555 - 10563

Published: July 29, 2022

Electron donor–acceptor (EDA) complexes provide a means to initiate radical reactions under visible light irradiation using substrates that do not absorb individually. Catalytic approaches complex formation are vital for advancing this synthetic strategy as it decouples the complexation and photogeneration of radicals from substrate functionalization, limitation inherent stoichiometric restricts structural diversity. This Synopsis highlights recent developments in EDA photochemistry which either donor or acceptor employed catalytically.

Language: Английский

Citations

85
Stereoselective amino acid synthesis by synergistic photoredox-pyridoxal radical biocatalysis DOI
Lei Cheng, Dian Li, Binh Khanh

et al.

Science, Journal Year: 2023, Volume and Issue: 381(6656), P. 444 - 451

Published: July 27, 2023

Developing synthetically useful enzymatic reactions that are not known in biochemistry and organic chemistry is an important challenge biocatalysis. Through the synergistic merger of photoredox catalysis pyridoxal 5'-phosphate (PLP) biocatalysis, we developed a radical biocatalysis approach to prepare valuable noncanonical amino acids, including those bearing stereochemical dyad or triad, without need for protecting groups. Using engineered PLP enzymes, either enantiomeric product could be produced biocatalyst-controlled fashion. Synergistic

Language: Английский

Citations

77
Using enzymes to tame nitrogen-centred radicals for enantioselective hydroamination DOI

Yuxuan Ye,

Jingzhe Cao,

Daniel G. Oblinsky

et al.

Nature Chemistry, Journal Year: 2022, Volume and Issue: 15(2), P. 206 - 212

Published: Nov. 14, 2022

Language: Английский

Citations

76
Tetrachlorophthalimides as Organocatalytic Acceptors for Electron Donor–Acceptor Complex Photoactivation DOI
Wei Zhou, Shuo Wu, Paolo Melchiorre

et al.

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(20), P. 8914 - 8919

Published: May 13, 2022

Excitation of photoactive electron donor-acceptor (EDA) complexes is an effective way to generate radicals. Applications in a catalytic regime typically use donors. Herein, we report that readily available electron-poor tetrachlorophthalimides can act as organocatalytic acceptors trigger the formation EDA with variety radical precursors not amenable previous methods. visible light generates carbon radicals under mild conditions. The versatility this complex platform allowed us develop mechanistically distinct reactions, including combination cobalt-based system. Quantum yield measurements established closed cycle operational, which hints at ability turn over and govern each cycle.

Language: Английский

Citations

72
Single-Electron Oxidation-Initiated Enantioselective Hydrosulfonylation of Olefins Enabled by Photoenzymatic Catalysis DOI

Qinglong Shi,

Xiu‐Wen Kang, Zhiyong Liu

et al.

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

Citations

36
Stereoselective amino acid synthesis by photobiocatalytic oxidative coupling DOI

Tian-Ci Wang,

Binh Khanh, Zheng Zhang

et al.

Nature, Journal Year: 2024, Volume and Issue: 629(8010), P. 98 - 104

Published: May 1, 2024

Language: Английский

Citations

31
From Ground-State to Excited-State Activation Modes: Flavin-Dependent “Ene”-Reductases Catalyzed Non-natural Radical Reactions DOI
Haigen Fu, Todd K. Hyster

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

Citations

20
Stereodivergent photobiocatalytic radical cyclization through the repurposing and directed evolution of fatty acid photodecarboxylases DOI
Shuyun Ju, Dian Li, Binh Khanh

et al.

Nature Chemistry, Journal Year: 2024, Volume and Issue: 16(8), P. 1339 - 1347

Published: April 17, 2024

Language: Английский

Citations

17
Directed Evolution and Unusual Protonation Mechanism of Pyridoxal Radical C–C Coupling Enzymes for the Enantiodivergent Photobiocatalytic Synthesis of Noncanonical Amino Acids DOI
Lei Cheng,

Zhiyu Bo,

Benjamin Krohn-Hansen

et al.

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 23, 2025

Visible light-driven pyridoxal radical biocatalysis has emerged as a new strategy for the stereoselective synthesis of valuable noncanonical amino acids in protecting-group-free fashion. In our previously developed dehydroxylative C–C coupling using engineered PLP-dependent tryptophan synthases, an enzyme-controlled unusual α-stereochemistry reversal and pH-controlled enantiopreference were observed. Herein, through high-throughput photobiocatalysis, we evolved set stereochemically complementary PLP enzymes, allowing both l- d-amino with enhanced enantiocontrol across broad pH window. These newly acid synthases permitted use range organoboron substrates, including boronates, trifluoroborates, boronic acids, excellent efficiency. Mechanistic studies unveiled unexpected racemase activity earlier enzyme variants. This promiscuous was abolished shedding light on origin enantiocontrol. Further mechanistic investigations suggest switch proton donor to account stereoinvertive formation highlighting stereoinversion mechanism that is rare conventional two-electron enzymology.

Language: Английский

Citations

2
Photoenzymatic Synthesis of α-Tertiary Amines by Engineered Flavin-Dependent “Ene”-Reductases DOI
Xin Gao,

Joshua Turek-Herman,

Young Joo Choi

et al.

Journal of the American Chemical Society, Journal Year: 2021, Volume and Issue: 143(47), P. 19643 - 19647

Published: Nov. 16, 2021

α-Tertiary amines are a common motif in pharmaceutically important molecules but challenging to prepare using asymmetric catalysis. Here, we demonstrate engineered flavin-dependent 'ene'-reductases (EREDs) can catalyze radical additions into oximes this motif. Two different EREDs were evolved competent catalysts for transformation with high levels of stereoselectivity. Mechanistic studies indicate that the oxime contributes enzyme templated charge-transfer complex formed between substrate and cofactor. These products be further derivatized variety motifs, highlighting versatility ERED photoenzymatic catalysis organic synthesis.

Language: Английский

Citations

68