Radical‐Based Synthesis and Modification of Amino Acids

Angewandte Chemie International Edition, Journal Year: 2020, Volume and Issue: 60(3), P. 1098 - 1115

Published: Aug. 26, 2020

Abstract Amino acids (AAs) are key structural motifs with widespread applications in organic synthesis, biochemistry, and material sciences. Recently, the development of milder more versatile radical‐based procedures, use strategies relying on radical chemistry for synthesis modification AAs has gained increased attention, as they allow rapid access to libraries novel unnatural containing a wide range motifs. In this Minireview, we provide broad overview advancements made field during last decade, focusing methods de novo α‐, β‐, γ‐AAs, well selective derivatisation canonical non‐canonical α‐AAs.

Language: Английский

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Recent advances in the synthesis of fluorinated amino acids and peptides

Chemical Communications, Journal Year: 2023, Volume and Issue: 59(11), P. 1434 - 1448

Published: Jan. 1, 2023

The site-selective modification of amino acids, peptides, and proteins has always been an intensive topic in organic synthesis, medicinal chemistry, chemical biology due to the vital role acids life. Among developed methods, introduction fluorine functionalities into peptides emerged as a useful approach change their physicochemical biological properties. With increasing demand for life science, direct fluorination/fluoroalkylation also received attention because unique properties atom(s) that can protein structure, increase lipophilicity, enable functionality tracer or probe studies. In this feature article, we summarized recent advances synthesis fluorinated wherein two strategies have discussed. One is based on building blocks prepare with diversified structures, including transformations imines nickel-catalyzed dicarbofunctionalization alkenes bromodifluoroacetate its derivatives; other fluorination/fluoroakylation proteins, which selective functional groups serine, threonine, tyrosine, tryptophan, cysteine lead wide range α-amino featuring synthetic convenience late-stage biomacromolecules. These complement each other, transition-metal catalysis new fluoroalkylating reagents provide powerful tools selectively access showing prospect chemistry biology.

Language: Английский

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Perfluorocarbons in Chemical Biology

ChemBioChem, Journal Year: 2020, Volume and Issue: 21(24), P. 3451 - 3462

Published: July 6, 2020

Perfluorocarbons, saturated carbon chains in which all the hydrogen atoms are replaced with fluorine, form a separate phase from both organic and aqueous solutions. Though perfluorinated compounds not found living systems, they can be used to modify biomolecules confer orthogonal behavior within natural such as improved stability, engineered assembly, cell-permeability. Perfluorinated groups also provide handles for purification, mass spectrometry, 19 F NMR studies complex environments. Herein, we describe how unique properties of perfluorocarbons have been employed understand manipulate biological systems.

Language: Английский

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Hypervalent Iodine‐Mediated Late‐Stage Peptide and Protein Functionalization

Angewandte Chemie International Edition, Journal Year: 2021, Volume and Issue: 61(7)

Published: Oct. 21, 2021

Hypervalent iodine compounds are powerful reagents for the development of novel transformations. As they exhibit low toxicity, high functional group tolerance, and stability in biocompatible media, have been used functionalization biomolecules. Herein, we report recent advances up to June 2021 peptide protein modification using hypervalent reagents. Their use as transfer or oxidizing is discussed this Minireview, including methods targeting polar, aromatic, aliphatic amino acids termini.

Language: Английский

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Non-Canonical Amino Acids as Building Blocks for Peptidomimetics: Structure, Function, and Applications

Biomolecules, Journal Year: 2023, Volume and Issue: 13(6), P. 981 - 981

Published: June 12, 2023

This review provides a fresh overview of non-canonical amino acids and their applications in the design peptidomimetics. Non-canonical appear widely distributed nature are known to enhance stability specific secondary structures and/or biological function. Contrary ubiquitous DNA-encoded acids, structure function these residues not fully understood. Here, results from experimental molecular modelling approaches gathered classify several classes according ability induce yielding different functions improved stability. Regarding side-chain modifications, symmetrical asymmetrical α,α-dialkyl glycines, Cα cyclized proline analogues, β-substituted α,β-dehydro some representatives addressed. Backbone modifications were also examined, especially those that result retro-inverso peptidomimetics depsipeptides. All this knowledge has an important application field peptidomimetics, which is continuous progress promises deliver new biologically active molecules materials near future.

Language: Английский

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Single electron transfer-based peptide/protein bioconjugations driven by biocompatible energy input

Communications Chemistry, Journal Year: 2020, Volume and Issue: 3(1)

Published: Nov. 13, 2020

Abstract Bioconjugation reactions play a central facilitating role in engendering modified peptides and proteins. Early progress this area was inhibited by challenges such as the limited range of substrates relatively poor biocompatibility bioconjugation reagents. However, recent developments visible-light induced photoredox catalysis electrochemical have permitted significant novel reactivities to be developed field synthetic chemistry. This perspective describes advances use biocompatible energy input for modification proteins mainly, via single electron transfer (SET) process, well key future area.

Language: Английский

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Rapid Biomolecular Trifluoromethylation Using Cationic Aromatic Sulfonate Esters as Visible-Light-Triggered Radical Photocages

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(42), P. 22878 - 22884

Published: Oct. 11, 2023

Described here is a photodecaging approach to radical trifluoromethylation of biomolecules. This was accomplished by designing quinolinium sulfonate ester that, upon absorption visible light, achieves decaging via photolysis the ultimately liberate free trifluoromethyl radicals that are trapped π-nucleophiles in process enables protein and protein-interaction mapping experiments using require only 1 s reaction times low photocage concentrations. In these experiments, aromatic side chains labeled an environmentally dependent fashion, with selectivity observed for tryptophan (Trp), followed histidine (His) tyrosine (Tyr). Scalable peptide through also demonstrated, where bespoke peptides harboring groups at residues can be synthesized 5-7 min good yields.

Language: Английский

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Metal‐Catalyzed C(sp²)−H Functionalization Processes of Phenylalanine‐ and Tyrosine‐Containing Peptides

European Journal of Inorganic Chemistry, Journal Year: 2021, Volume and Issue: 2021(29), P. 2928 - 2941

Published: June 14, 2021

Abstract The site‐selective chemical diversification of biomolecules constitutes an unmet challenge capital importance within medicinal chemistry and biology. functionalization otherwise unreactive C−H bonds holds great promise for reducing the reliance on existing functional groups, thereby streamlining syntheses. Over last years, a myriad peptide labelling techniques featuring metal‐catalyzed reactions have been developed. Despite wealth reports in field, modification both phenylalanine (Phe) tyrosine (Tyr) compounds upon metal catalysis remain comparatively overlooked. This review highlights these promising tagging strategies, which generally occur through formation challenging 6‐membered metallacycles enable late‐stage peptides tailored fashion.

Language: Английский

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Harnessing photocatalytic and electrochemical approaches for C–H bond trifluoromethylation and fluoroalkylation

Organic Chemistry Frontiers, Journal Year: 2023, Volume and Issue: 11(3), P. 954 - 1014

Published: Dec. 14, 2023

The review summarises various photo- and electrochemical strategies for trifluoromethylation fluoroalkylation of different C(sp 3 )–H, 2 C(sp)–H bonds in several classes organic molecules.

Language: Английский

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Radikal‐basierte Synthese und Modifikation von Aminosäuren

Angewandte Chemie, Journal Year: 2020, Volume and Issue: 133(3), P. 1112 - 1130

Published: Aug. 26, 2020

Abstract Aminosäuren (AS) sind wichtige Strukturmotive mit vielfältigen Anwendungsmöglichkeiten in der organischen Synthese, Biochemie und den Materialwissenschaften. In jüngster Zeit hat Entwicklung milderer vielseitigerer Verfahren Einsatz von radikalchemischen Methoden für die Synthese Modifikation AS größere Aufmerksamkeit gewonnen, da sie einen schnellen Zugang zu einer Vielzahl neuartiger unnatürlicher (UAS) breiten Palette Strukturmotiven ermöglichen. diesem Kurzaufsatz geben wir umfassenden Überblick über Fortschritte, Bereich letzten zehn Jahren erzielt wurden konzentrieren uns dabei auf De‐novo‐Synthese α‐,β‐ γ‐AS sowie selektive Derivatisierung kanonischer nichtkanonischer AS.

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