Cu-Catalysed Coupling of Aliphatic Amines with Alkylboronic Esters DOI Creative Commons
Francesca M. Dennis, Antonio Romero‐Arenas, George Rodgers

и другие.

Опубликована: Июль 29, 2022

We report a Cu-catalysed oxidative coupling of aliphatic amines with alkylboronic esters to give high value alkyl amines, products found widely in applications from medicinal chemistry materials science. This operationally simple reaction, which can be performed on gram scale, runs under mild conditions and exhibits excellent functional group tolerance. The terminal oxidant the reaction is O2 air, avoiding need for additional chemical oxidants. Investigation into mechanism suggests intermediacy an radical, generated boronic ester upon activation through amino radical transfer process. To demonstrate its utility potential late-stage functionalization, we showcase method as final step total synthesis TRPV 1 antagonist.

Язык: Английский

Biocatalytic reductive aminations with NAD(P)H-dependent enzymes: enzyme discovery, engineering and synthetic applications DOI
Bo Yuan, Dameng Yang, Ge Qu

и другие.

Chemical Society Reviews, Год журнала: 2023, Номер 53(1), С. 227 - 262

Опубликована: Дек. 7, 2023

This review summarized NAD(P)H-dependent amine dehydrogenases and imine reductases which catalyzes asymmetric reductive amination to produce optically active amines.

Язык: Английский

Процитировано

30

Stereoselective construction of β-, γ- and δ-lactam rings via enzymatic C–H amidation DOI
Satyajit Roy, David A. Vargas, Pengchen Ma

и другие.

Nature Catalysis, Год журнала: 2023, Номер 7(1), С. 65 - 76

Опубликована: Дек. 6, 2023

Язык: Английский

Процитировано

29

Computational Redesign of the Substrate Binding Pocket of Glutamate Dehydrogenase for Efficient Synthesis of Noncanonical l-Amino Acids DOI
Ziyuan Wang, Haisheng Zhou, Haoran Yu

и другие.

ACS Catalysis, Год журнала: 2022, Номер 12(21), С. 13619 - 13629

Опубликована: Окт. 24, 2022

Noncanonical amino acids are attractive molecules in synthetic chemistry as important building blocks for pharmaceuticals and agrochemicals. Asymmetric reductive amination of prochiral keto catalyzed by glutamate dehydrogenase (GluDH) is an efficient process the production these molecules. However, stringent substrate specificity lack engineering strategy hampered its wide application substrate-oriented chiral carbon–nitrogen bond formation. To address this issue, first, recognition mechanism GluDH was investigated using CdGluDH (an NADH-dependent from Clostridium difficile) four including natural three non-natural substrates models through computational simulation experimental verification. Second, a based on reducing pocket steric hindrance tuning enzyme–substrate electrostatic interactions and/or X–H···π developed to systematically redesign binding with mutations 10 sites accept distinct substrates. As result, tailor-made variants were created synthesize corresponding high-value products, l-norvaline, l-phosphinothricin, l-homophenylalanine, specific activities improved 2.3-fold, 916.2-fold, no activity 66.64 U/mg, respectively. Finally, efficiency tested simulated industrial catalytic reaction, demonstrating that enzyme promising enhancing noncanonical GluDHs.

Язык: Английский

Процитировано

30

Electrochemical transformations catalyzed by cytochrome P450s and peroxidases DOI Creative Commons
Neeraj Kumar, Jie He, James F. Rusling

и другие.

Chemical Society Reviews, Год журнала: 2023, Номер 52(15), С. 5135 - 5171

Опубликована: Янв. 1, 2023

The electrochemistry of heme-containing enzymes (including cytochrome P450s and peroxidases) their applications in electrosynthesis are reviewed.

Язык: Английский

Процитировано

21

Enzymatic Oxy‐ and Amino‐Functionalization in Biocatalytic Cascade Synthesis: Recent Advances and Future Perspectives DOI Creative Commons
Eleonora Grandi, Fatma Feyza Özgen, Sandy Schmidt

и другие.

Angewandte Chemie International Edition, Год журнала: 2023, Номер 62(48)

Опубликована: Авг. 28, 2023

Biocatalytic cascades are a powerful tool for building complex molecules containing oxygen and nitrogen functionalities. Moreover, the combination of multiple enzymes in one pot offers possibility to minimize downstream processing waste production. In this review, we illustrate various recent efforts development multi-step syntheses involving C-O C-N bond-forming produce high value-added compounds, such as pharmaceuticals polymer precursors. Both vitro vivo examples discussed, revealing respective advantages drawbacks. The use engineered boost outcome is also addressed current co-substrate cofactor recycling strategies presented, highlighting importance atom economy. Finally, tools overcome challenges multi-enzymatic oxy- amino-functionalization reactions including flow systems with immobilized biocatalysts confined nanomaterials.

Язык: Английский

Процитировано

19

Peptide and Enzyme Catalysts Work in Concert in Stereoselective Cascade Reactions—Oxidation followed by Conjugate Addition DOI Creative Commons

Jasper S. Möhler,

Mathias Pickl, Tamara Reiter

и другие.

Angewandte Chemie International Edition, Год журнала: 2024, Номер 63(12)

Опубликована: Янв. 18, 2024

Abstract Enzymes and peptide catalysts consist of the same building blocks but require vastly different environments to operate best. Herein, we show that an enzyme a catalyst can work together in single reaction vessel catalyze two‐step cascade with high chemo‐ stereoselectivity. Abundant linear alcohols, nitroolefins, alcohol oxidase, tripeptide provided chiral γ‐nitroaldehydes aqueous buffer. High yields (up 92 %) stereoselectivities 98 % ee) were achieved for through rational design identification common conditions.

Язык: Английский

Процитировано

6

Oxygenating Biocatalysts for Hydroxyl Functionalisation in Drug Discovery and Development DOI
Sacha N. Charlton, Martin A. Hayes

ChemMedChem, Год журнала: 2022, Номер 17(12)

Опубликована: Апрель 6, 2022

C-H oxyfunctionalisation remains a distinct challenge for synthetic organic chemists. Oxygenases and peroxygenases (grouped here as "oxygenating biocatalysts") catalyse the oxidation of substrate with molecular oxygen or hydrogen peroxide oxidant. The application oxygenating biocatalysts in synthesis has dramatically increased over last decade, producing complex compounds potential uses pharmaceutical industry. This review will focus on hydroxyl functionalisation using tool drug discovery development. Established biocatalysts, such cytochrome P450s flavin-dependent monooxygenases, have widely been adopted this purpose, but can suffer from low activity, instability limited scope. Therefore, emerging which offer an alternative also be covered, well considering ways these hydroxylation biotransformations applied development, late-stage (LSF) biocatalytic cascades.

Язык: Английский

Процитировано

23

Construction of Chemoenzymatic Linear Cascades for the Synthesis of Chiral Compounds DOI Creative Commons
Christian Ascaso‐Alegre, Juan Mangas‐Sánchez

European Journal of Organic Chemistry, Год журнала: 2022, Номер 2022(22)

Опубликована: Май 16, 2022

Abstract Inspired by nature, synthetic chemists try to mimic the efficient metabolic networks in living organisms build complex molecules combining different types of catalysts same reaction vessel. These multistep cascade processes provide many advantages procedures, resulting higher productivities with lower waste generation and cost. However, chemo‐ biocatalysts can be challenging as conditions might differ greatly. As a highly multidisciplinary field that benefits from advances chemical catalysis, molecular biology engineering, this area study is rapidly progressing. In Review, we highlight recent trends construction chemoenzymatic one‐pot cascades access chiral compounds well strategies solve current challenges field.

Язык: Английский

Процитировано

20

Cu‐Catalyzed Coupling of Aliphatic Amines with Alkylboronic Esters DOI Creative Commons
Francesca M. Dennis, Antonio Romero‐Arenas, George Rodgers

и другие.

Chemistry - A European Journal, Год журнала: 2024, Номер 30(19)

Опубликована: Янв. 3, 2024

Abstract We report a Cu‐catalyzed oxidative coupling of aliphatic amines with benzylic and boronic esters to give high value alkyl amines, products found widely in applications from medicinal chemistry materials science. This operationally simple reaction, which can be performed on gram scale, runs under mild conditions exhibits broad functional group tolerance. The terminal oxidant the reaction is O 2 air, avoiding need for additional chemical oxidants. Investigation into mechanism suggests that ester activated by an aminyl radical, formed through oxidation amine Cu catalyst, key radical intermediate. To demonstrate its utility potential late‐stage functionalization, we showcase method as final step total synthesis TRPV1 antagonist.

Язык: Английский

Процитировано

5

A refined picture of the native amine dehydrogenase family revealed by extensive biodiversity screening DOI Creative Commons
Eddy Elisée, Laurine Ducrot, Raphaël Méheust

и другие.

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Июнь 10, 2024

Язык: Английский

Процитировано

5