Chemoselective Reduction of Barbiturates by Photochemically Excited Flavin Catalysts DOI
Golo Storch,

Richard Foja,

Alexandra Walter

et al.

Synlett, Journal Year: 2023, Volume and Issue: 35(09), P. 952 - 956

Published: Oct. 30, 2023

Abstract Photocatalytic reductive cyclizations are powerful methods for obtaining structurally complex molecules. Achieving noninherent reactivity in substrates with more than one potential site of reduction is a difficult challenge. We disclose the use flavin catalysis chemoselective cyclization barbiturates additional reactive functional groups. Our method provides orthogonal selectivity comparison to well-established reductant samarium(II) iodide, which preferentially reduces substrate ketone Flavin first leads barbiturate and allows complete change chemoselectivity appended ketones. Additionally, photocatalysis enables oxime ethers >99% yield, not possible SmI2.

Language: Английский

Synergistic Photoenzymatic Anti-Markovnikov Hydroarylation of Olefins via Heteroaryl Radical Intermediates DOI
Prasun Mukherjee,

Zayed Alassad,

Todd K. Hyster

et al.

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

Published: April 16, 2025

Heteroaromatic alkylations are indispensable reactions for synthesizing biologically active molecules. The anti-Markovnikov hydroarylation of olefins using heteroaryl halides furnishes the product as a single regioisomer; however, catalytic variants ineffective at controlling stereochemical outcome these reactions. Here, we report synergistic photoenzymatic flavin-dependent "ene"-reductases with ruthenium photoredox catalysts. Enzyme homologues were identified, which provide access to both enantiomers in greater than 80% yield up 99:1 er. This method is effective styrenyl- and unactivated alkenes, highlighting generality this approach. highest yielding system involves carboxylated photocatalyst increased affinity enzyme. work expands types radical intermediates that enzymes can use stereoselective intermolecular coupling

Language: Английский

Citations

0
Transitioning enzyme catalysis towards photocatalysis DOI Creative Commons
Nigel S. Scrutton, Sam Hay, Derren J. Heyes

et al.

Philosophical Transactions of the Royal Society A Mathematical Physical and Engineering Sciences, Journal Year: 2025, Volume and Issue: 383(2296)

Published: May 8, 2025

Enzyme biocatalysis is being industrialized at a phenomenal rate. Biocatalysis offers routes to chemical transformations that avoid the use of expensive metal catalysts, high temperatures and pressures, while providing impressive enantio-, regio- chemo-selectivities. Working individually or as cascades, in live cells cell-free preparations, manufacture everyday chemicals, materials, healthcare products, fuels pharmaceuticals diagnostic industrial sensing applications, enzymes are key enablers circular bioeconomy. An ability exploit tailor biocatalysts rapidly predictably requires knowledge structure-mechanism relationships physical chemistry enzyme action. This has advanced since our millennium article on this topic (Sutcliffe Scrutton Phil Trans R. Soc. Lond. A . 2000. 358, 367–386). Here, we discuss an emerging frontier—enzyme photobiocatalysis. Photoenzymes rarely found nature. limits 'difficult-to-achieve' reactions biology generally accessible photocatalysts. We here emergence photobiocatalysis new frontier. review natural photoenzymes identify challenges limitations their photobiocatalysts. consider reports repurposing also prospects for de novo design photobiocatalysts which general concept would transform catalysis science. part theme issue ‘Science into next millennium: 25 years on’.

Language: Английский

Citations

0
Bridging chemistry and biology for light-driven new-to-nature enantioselective photoenzymatic catalysis DOI
Xinjie Yang,

Jianjian Huang,

Juan Guo

et al.

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

Citations

0
Regiodivergent Radical Termination for Intermolecular Biocatalytic C–C Bond Formation DOI Creative Commons
Mark Petchey,

Yuxuan Ye,

Victor Spelling

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(7), P. 5005 - 5010

Published: Feb. 8, 2024

Radical hydrofunctionalizations of electronically unbiased dienes are challenging to render regioselective, because the products nearly identical in energy. Here, we report two engineered FMN-dependent "ene"-reductases (EREDs) that catalyze regiodivergent hydroalkylations cyclic and linear dienes. While previous studies focused exclusively on stereoselectivity alkene hydroalkylation, this work highlights EREDs can control regioselectivity hydrogen atom transfer, providing a method for selectively preparing constitutional isomers would be prepare using traditional synthetic methods. Engineering ERED from Gluconabacter sp. (GluER) furnished variant favors γ,δ-unsaturated ketone, while an commercial panel δ,ε-unsaturated ketone. The effect beneficial mutations has been investigated substrate docking mechanism probed by isotope labeling experiments. A variety α-bromo ketones coupled with These interesting building blocks also further modified generate difficult-to-access heterocyclic compounds.

Language: Английский

Citations

3
Allylsilane as a versatile handle in photoredox catalysis DOI

Nand Lal,

Sanket B. Shirsath,

P. R. SINGH

et al.

Chemical Communications, Journal Year: 2024, Volume and Issue: 60(35), P. 4633 - 4647

Published: Jan. 1, 2024

This review briefly summarizes the utilization of allylsilane in photoredox catalysis. It highlights underlying mechanisms for formation C–C/C–heteroatom bond with various functionalities mild conditions high selectivity.

Language: Английский

Citations

3
Unlocking the function promiscuity of old yellow enzyme to catalyze asymmetric Morita-Baylis-Hillman reaction DOI Creative Commons
Lei Wang, Yaoyun Wu, Jun Hu

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: July 9, 2024

Abstract Exploring the promiscuity of native enzymes presents a promising strategy for expanding their synthetic applications, particularly catalyzing challenging reactions in non-native contexts. In this study, we explore promiscuous potential old yellow (OYEs) to facilitate Morita-Baylis-Hillman reaction (MBH reaction), leveraging substrate similarities between MBH and reduction reaction. Using mass spectrometry spectroscopic techniques, confirm Gk OYE both reactions. By blocking H - + transfer pathways, engineer OYE.8, which loses its ability but enhances activity. The structural basis catalyzed by OYE.8 is obtained through mutation studies kinetic simulations. Furthermore, enantiocomplementary mutants OYE.11 OYE.13 are directed evolution, exhibiting accept various aromatic aldehydes alkenes as substrates. This study demonstrates unlock enzyme functionalities, enabling catalysis new-to-nature

Language: Английский

Citations

3
Non‐native Intramolecular Radical Cyclization Catalyzed by a B12‐Dependent Enzyme** DOI Creative Commons
Jianbin Li, Amardeep Kumar, Jared C. Lewis

et al.

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(51)

Published: Oct. 24, 2023

Despite the unique reactivity of vitamin B

Language: Английский

Citations

4
Engineering a photoenzyme to use red light DOI
J. M. Carceller, Bhumika Jayee, Claire G. Page

et al.

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

Published: Oct. 1, 2024

Language: Английский

Citations

1
Non‐native Intramolecular Radical Cyclization Catalyzed by a B12‐Dependent Enzyme** DOI Creative Commons
Jianbin Li, Amardeep Kumar, Jared C. Lewis

et al.

Angewandte Chemie, Journal Year: 2023, Volume and Issue: 135(51)

Published: Oct. 24, 2023

Abstract Despite the unique reactivity of vitamin B 12 and its derivatives, ‐dependent enzymes remain underutilized in biocatalysis. In this study, we repurposed transcription factor CarH to enable non‐native radical cyclization reactions. An engineered variant enzyme, CarH*, catalyzes formation γ‐ δ‐lactams through either redox‐neutral or reductive ring closure with marked enhancement selectivity relative free cofactor. CarH* also an unusual spirocyclization by dearomatization pendant arenes produce bicyclic 1,3‐diene products instead 1,4‐dienes provided existing methods. These results associated mechanistic studies highlight importance protein scaffolds for controlling expanding synthetic utility enzymes.

Language: Английский

Citations

1
Photoenzymatic Enantioselective Synthesis of Oxygen‐Containing Benzo‐Fused Heterocycles DOI

Changtong Zhu,

Zhenbo Yuan, Zhiwei Deng

et al.

Angewandte Chemie, Journal Year: 2023, Volume and Issue: 135(50)

Published: Oct. 30, 2023

Abstract New‐to‐nature biocatalysis in organic synthesis has recently emerged as a green and powerful strategy for the preparation of valuable chiral products, among which oxygen‐containing benzo‐fused heterocycles are important structural motifs pharmaceutical industry. However, asymmetric these compounds through radical‐mediated methods is challenging. Herein, novel photoenzymatic developed to realize efficient enantioselective structure‐guided engineering flavin‐dependent ‘ene’‐reductase GluER. It shows that variant GluER‐W100H could efficiently produce various benzoxepinones, chromanone indanone with different rings high yields great stereoselectivities under visible light. Moreover, results well supported by mechanistic experiments, revealing this process involves electron donor‐acceptor complex formation, single transfer hydrogen atom transfer. Therefore, we provide an alternative approach chemoenzymatic skeletons bioactive pharmaceuticals.

Language: Английский

Citations

1