Copper-dependent halogenase catalyses unactivated C−H bond functionalization

Nature, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 29, 2025

Language: Английский

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Ground-state flavin-dependent enzymes catalyzed enantioselective radical trifluoromethylation

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 31, 2025

Language: Английский

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Chemoenzymatic synthesis

Communications Chemistry, Journal Year: 2025, Volume and Issue: 8(1)

Published: March 13, 2025

Communications Chemistry is pleased to introduce a Collection of research works focused on recent developments within the interdisciplinary field chemoenzymatic synthesis. Here, Guest Editors highlight key themes and look towards future this field.

Language: Английский

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Catalytic Enantioselective Smiles Rearrangement Enabled by the Directed Evolution of P450 Radical Aryl Migratases

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

Published: April 1, 2025

Despite its synthetic potential, catalytic enantioselective Smiles rearrangement has remained elusive. Through the directed evolution of P450 radical aryl migratases (P450Smiles's), we describe first example rearrangement. A range racemic N-arylsulfonyl-α-chloroamides could be transformed by P450Smiles in an enantioconvergent manner, affording acyclic amide products possessing all-carbon quaternary stereocenter with excellent chemo- and enantioselectivity. Both electron-rich electron-deficient substituents were compatible migrating group, demonstrating this P450-catalyzed is insensitive to electronic properties group. Importantly, our evolved variants capable overriding innate cyclization activity N-alkyl amidyl intermediate, allowing chemoselective reductive formation products. Classical molecular dynamics (MD) simulations revealed unusual enzyme-controlled chemoselectivity stems from restricted conformation within enzyme active site, disfavoring pathway. This new-to-nature biocatalytic asymmetric showcases potential enzymatic enantioselectivity control over highly reactive intermediates eluding small-molecule catalysts.

Language: Английский

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Merging photoredox with metalloenzymatic catalysis for enantioselective decarboxylative C(sp3)‒N3 and C(sp3)‒SCN bond formation

Nature Catalysis, Journal Year: 2024, Volume and Issue: 7(12), P. 1394 - 1403

Published: Dec. 20, 2024

Language: Английский

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Biocatalytic Generation of Trifluoromethyl Radicals by Nonheme Iron Enzymes for Enantioselective Alkene Difunctionalization

Published: Aug. 19, 2024

The trifluoromethyl (–CF3) group represents a highly prevalent functionality in pharmaceuticals. Over the past few decades, significant advances have been made development of synthetic methods for trifluoromethylation. In contrast, there are currently no metalloenzymes known to catalyze formation C(sp3)‒CF3 bonds. this work, we demonstrate that nonheme iron enzyme, hydroxymandelate synthase from Amycolatopsis orientalis (AoHMS), is capable generating CF3 radicals hypervalent iodine(III) reagents and directing them enantioselective alkene azidation. A high-throughput screening (HTS) platform based on Staudinger ligation was established, enabling rapid evaluation AoHMS variants abiological transformation. final opti-mized variant accepts range substrates, producing azidation products up 73% yield 96:4 enanti-omeric ratio (e.r.). biocatalytic can be further extended pentafluoroethyl diazidation by altering reagent. addition, anion competition experiments provide insights into radical rebound process This study not only expands catalytic repertoire transformations but also creates new enzymatic space organofluorine synthesis.

Language: Английский

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Biocatalytic Generation of Trifluoromethyl Radicals by Nonheme Iron Enzymes for Enantioselective Alkene Difunctionalization

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 5, 2024

The trifluoromethyl (-CF

Language: Английский

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Biocatalytic Generation of Trifluoromethyl Radicals by Nonheme Iron Enzymes for Enantioselective Alkene Difunctionalization

Published: Aug. 16, 2024

The trifluoromethyl (–CF3) group represents a highly prevalent functionality in pharmaceuticals. Over the past few decades, significant advances have been made development of synthetic methods for trifluoromethylation. In contrast, there are currently no metal-loenzymes known to catalyze formation C(sp3)‒CF3 bonds. this work, we demonstrate that nonheme iron enzyme, hydroxy-mandelate synthase from Amycolatopsis orientalis (AoHMS), is capable generating CF3 radicals hypervalent iodine(III) reagents and directing them enantioselective alkene azidation. A high-throughput screening (HTS) platform based on Staudinger ligation was established, enabling rapid evaluation AoHMS variants abiological transformation. final opti-mized variant accepts range substrates, producing azidation products up 73% yield 96:4 enanti-omeric ratio (e.r.). biocatalytic can be further extended pentafluoroethyl diazidation by altering reagent. addition, anion competition experiments provide insights into radical rebound process This study not only expands catalytic repertoire metalloenzymes transformations but also creates new enzymatic space organofluorine synthesis.

Language: Английский

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Chemoenzymatic Synthesis of Fluorinated L-α-Amino Acids

ACS Sustainable Chemistry & Engineering, Journal Year: 2024, Volume and Issue: 12(36), P. 13645 - 13653

Published: Aug. 27, 2024

Fluorinated amino acids play a crucial role as fundamental components in drug synthesis owing to their favorable attributes that enhance the pharmacokinetic properties of drugs. Nevertheless, conventional chemical fluorinated faces challenges achieving stereoselectivity control. Additionally, high cost substrates and intricate cofactor recycling process enzymatic have limited industrial production applications. In this study, we developed three-step chemoenzymatic cascade for asymmetric chiral acids. The methodology involves utilization variety cost-effective aldehydes starting materials, enabling economical aldol reactions catalyzed by aldolase. Subsequent decarboxylation produces reductive amination through phenylalanine ammonia lyase, resulting diverse library aromatic l-α-amino acid products with relative yield enantiomeric purity (up 99%). Furthermore, synthesized three pharmaceutically relevant on preparative scale using whole-cell biocatalysts, demonstrating versatility approach. This study has introduced simplified, efficient, route synthesizing under mild conditions, offering insights into valuable fluorine-containing pharmaceuticals other biologically active compounds.

Language: Английский

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Recent progress in asymmetric radical reactions enabled by chiral iron catalysts

Chemical Communications, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 1, 2024

In this highlight, we discuss recently developed chiral iron catalysts and their application in radical asymmetric reactions for the construction of axial or central chirality.

Language: Английский

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