Asymmetric Synthesis of 2-Arylethylamines: A Metal-Free Review of the New Millennium DOI Creative Commons
Alejandro Manchado, Ángel García-González, Carlos T. Nieto

et al.

Molecules, Journal Year: 2024, Volume and Issue: 29(23), P. 5729 - 5729

Published: Dec. 4, 2024

2-Arylethylamines are presented in several natural bioactive compounds, as well nitrogen-containing drugs. Their ability to surpass the blood-brain barrier makes this family of compounds especial interest medicinal chemistry. Asymmetric methodologies towards synthesis 2-arylethylamine motives great due challenges they may present. Thus, a concise metal-free review presenting recent advances asymmetric 2-arylethylamines is presented, covering last-millennium studies, considering different aforementioned motif, including chiral induction, organocatalysis, organophotocatalysis and enzymatic catalysis.

Language: Английский

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
Asymmetric photoenzymatic incorporation of fluorinated motifs into olefins DOI
Mao‐Lin Li, Yaru Yuan, Wesley Harrison

et al.

Science, Journal Year: 2024, Volume and Issue: 385(6707), P. 416 - 421

Published: July 25, 2024

Enzymes capable of assimilating fluorinated feedstocks are scarce. This situation poses a challenge for the biosynthesis compounds used in pharmaceuticals, agrochemicals, and materials. We developed photoenzymatic hydrofluoroalkylation that integrates motifs into olefins. The photoinduced promiscuity flavin-dependent ene-reductases enables generation carbon-centered radicals from iodinated fluoroalkanes, which directed by photoenzyme to engage enantioselectively with approach facilitates stereocontrol through interaction between singular unit enzyme, securing high enantioselectivity at β, γ, or δ positions groups enzymatic hydrogen atom transfer-a process is notably challenging conventional chemocatalysis. work advances strategies integrating chemical opens avenues asymmetric synthesis compounds.

Language: Английский

Citations

15
Threonine Aldolase-Catalyzed Enantioselective α-Alkylation of Amino Acids through Unconventional Photoinduced Radical Initiation DOI

Tian-Ci Wang,

Zheng Zhang, Guodong Rao

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(32), P. 22476 - 22484

Published: July 4, 2024

Visible light-driven pyridoxal radical biocatalysis has emerged as a promising strategy for the stereoselective synthesis of valuable noncanonical amino acids (ncAAs). Previously, use well-tailored photoredox catalysts represented key to enable efficient phosphate (PLP) enzyme-catalyzed reactions. Here, we report PLP-dependent threonine aldolase-catalyzed asymmetric α-C–H alkylation abundant using Katritzky pyridinium salts alkylating agents. The engineered aldolases allowed this redox-neutral proceed efficiently, giving rise challenging α-trisubstituted and -tetrasubstituted ncAA products in protecting-group-free fashion with excellent enantiocontrol. Mechanistically, enantioselective α-alkylation capitalizes on unique reactivity persistent enzymatic quinonoid intermediate derived from PLP cofactor acid substrate allow novel C–C coupling. Surprisingly, photobiocatalytic process does not require well-established operates through an unconventional photoinduced generation involving PLP-derived aldimine. ability develop reactions without relying classic photocatalysts or photoenzymes opens up new avenues advancing intermolecular that are known either organic chemistry enzymology.

Language: Английский

Citations

7
Current Status of Amine Dehydrogenases: From Active Site Architecture to Diverse Applications Across a Broad Substrate Spectrum DOI Creative Commons
Vasilis Tseliou, Marcelo F. Masman, Tanja Knaus

et al.

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

Published: Sept. 3, 2024

Abstract Amine dehydrogenases (AmDHs) are NAD(P)H‐dependent oxidoreductases that catalyze the reductive amination between carbonyl compounds and ammonia as amine donor yielding valuable amines, typically with excellent enantioselectivity. While nature has provided enzymes inherent AmDH activities, protein engineering techniques allowed researchers to expand toolbox of available AmDHs, extend their substrate scope, improve catalytic activities stability under synthetically relevant conditions even enable new reactivity concepts. The biocatalytic synthesis amines using AmDHs matured a point where hundreds aldehydes or ketones, varying steric demands bearing diverse functional groups, can be efficiently transformed. This review offers an overview spectrum, covering from structural evolutionary analyses methods employing these enzymes. Depending on other reaction partners, were applied in kinetic resolution (KR) deracemization processes, cascade reactions for alcohols alkenes amino featuring multiple stereogenic centers. Moreover, synthetic potential novel pathways, such secondary alcohols, presents exciting opportunities expanding repertoire.

Language: Английский

Citations

4
Enantioselective biosynthesis of vicinal diamines enabled by synergistic photo/biocatalysis consisting of an ene-reductase and a green-light-excited organic dye DOI

Fengming Shi,

Bin Chen, Jinhai Yu

et al.

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

Published: Jan. 1, 2025

Language: Английский

Citations

0
“Excited” Class I Aldolases: EDA Complex Mediated Photo-biocatalytic Enantioselective β-Alkylation of Enals DOI
Sangoji Dheeraj,

Shahana Pulikkathodi,

Surabhi Odam Valappil

et al.

ACS Catalysis, Journal Year: 2025, Volume and Issue: unknown, P. 2531 - 2539

Published: Jan. 27, 2025

Language: Английский

Citations

0
Mechanistic investigation of repurposed photoenzymes with new-to-nature reactivity DOI
Zhengyi Zhang, Mao‐Lin Li, Huimin Zhao

et al.

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

Published: Feb. 27, 2025

Language: Английский

Citations

0
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
Design and Evolution of an Artificial Friedel–Crafts Alkylation Enzyme Featuring an Organoboronic Acid Residue DOI

Shu‐Bin Mou,

Kai‐Yue Chen,

Thittaya Kunthic

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(39), P. 26676 - 26686

Published: Aug. 27, 2024

Creating artificial enzymes by the genetic incorporation of noncanonical amino acids with catalytic side chains would expand enzyme chemistries that have not been discovered in nature. Here, we report design an uses

Language: Английский

Citations

2
Asymmetric Synthesis of 2-Arylethylamines: A Metal-Free Review of the New Millennium DOI Creative Commons
Alejandro Manchado, Ángel García-González, Carlos T. Nieto

et al.

Molecules, Journal Year: 2024, Volume and Issue: 29(23), P. 5729 - 5729

Published: Dec. 4, 2024

2-Arylethylamines are presented in several natural bioactive compounds, as well nitrogen-containing drugs. Their ability to surpass the blood-brain barrier makes this family of compounds especial interest medicinal chemistry. Asymmetric methodologies towards synthesis 2-arylethylamine motives great due challenges they may present. Thus, a concise metal-free review presenting recent advances asymmetric 2-arylethylamines is presented, covering last-millennium studies, considering different aforementioned motif, including chiral induction, organocatalysis, organophotocatalysis and enzymatic catalysis.

Language: Английский

Citations

0