Photocatalytic Late-Stage C–H Functionalization

Chemical Reviews, Journal Year: 2023, Volume and Issue: 123(8), P. 4237 - 4352

Published: Jan. 24, 2023

The emergence of modern photocatalysis, characterized by mildness and selectivity, has significantly spurred innovative late-stage C–H functionalization approaches that make use low energy photons as a controllable source. Compared to traditional strategies, photocatalysis paves the way toward complementary and/or previously unattainable regio- chemoselectivities. Merging compelling benefits with workflow offers potentially unmatched arsenal tackle drug development campaigns beyond. This Review highlights photocatalytic strategies small-molecule drugs, agrochemicals, natural products, classified according targeted bond newly formed one. Emphasis is devoted identifying, describing, comparing main mechanistic scenarios. draws critical comparison between established ionic chemistry photocatalyzed radical-based manifolds. aims establish current state-of-the-art illustrate key unsolved challenges be addressed in future. authors aim introduce general readership functionalization, specialist practitioners evaluation methodologies, potential for improvement, future uncharted directions.

Language: Английский

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Visible-Light-Mediated Modification and Manipulation of Biomacromolecules

Chemical Reviews, Journal Year: 2021, Volume and Issue: 122(2), P. 1752 - 1829

Published: Sept. 21, 2021

Chemically modified biomacromolecules─i.e., proteins, nucleic acids, glycans, and lipids─have become crucial tools in chemical biology. They are extensively used not only to elucidate cellular processes but also industrial applications, particularly the context of biopharmaceuticals. In order enable maximum scope for optimization, it is pivotal have a diverse array biomacromolecule modification methods at one's disposal. Chemistry has driven many significant advances this area, especially recently, numerous novel visible-light-induced photochemical approaches emerged. these reactions, light serves as an external source energy, enabling access highly reactive intermediates under exceedingly mild conditions with exquisite spatiotemporal control. While UV-induced transformations on biomacromolecules date back decades, visible unmistakable advantage being considerably more biocompatible, spectrum visible-light-driven now available, chiefly proteins acids. This review will discuss modifications native functional groups (FGs), including functionalization, labeling, cross-linking techniques well utility oxidative degradation mediated by photochemically generated oxygen species. Furthermore, non-native, bioorthogonal FGs be addressed, photoclick chemistry DNA-encoded library synthesis that allow manipulation activity biomacromolecule.

Language: Английский

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Recent advances in transition metal-mediated trifluoromethylation reactions

Chemical Communications, Journal Year: 2022, Volume and Issue: 58(75), P. 10442 - 10468

Published: Jan. 1, 2022

Fluorine compounds are known for their abundance in more than 20% of pharmaceutical and agrochemical products mainly due to the enhanced lipophilicity, metabolic stability pharmacokinetic properties organofluorides. Consequently, last decade has seen enormous growth incorporation a trifluoromethyl group into organic motifs. With significance, this review aims provide complete picture transition metal-mediated construction C(sp3, sp2, sp)-CF3 bonds via C-H/X bond functionalization or addition processes both aliphatic aromatic hydrocarbons. Diversified reagents ranging from radical electrophilic nucleophilic trifluoromethylating agents respective mechanisms have been further deliberated comprehensive overview. The coverage on topic is expected make unique beneficial future applications enriching community towards improvements field trifluoromethylation reactions, turn improving propensity development drugs.

Language: Английский

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Tryptophan-specific modification and diversification of peptides and proteins

Organic & Biomolecular Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

This review provides an account of the tryptophan-specific conjugation peptides and proteins its extensive application in imaging living cells, radiolabelling proteins, protein engineering, etc .

Language: Английский

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Solid‐State Radical C−H Trifluoromethylation Reactions Using Ball Milling and Piezoelectric Materials

Angewandte Chemie International Edition, Journal Year: 2020, Volume and Issue: 59(50), P. 22570 - 22576

Published: Sept. 14, 2020

Abstract The application of piezoelectricity for the generation trifluoromethyl (CF 3 ) radicals is reported together with development a method mechanochemical C−H trifluoromethylation aromatic compounds. As compared to conventional solution‐based approaches, this mechanoredox enables cleaner and more sustainable access wide range trifluoromethylated N‐heterocycles peptides, which are important structural motifs in modern drug discovery. This study thus represents an milestone future applications systems medicinal pharmaceutical science.

Language: Английский

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Late‐stage C−H Functionalization of Tryptophan‐Containing Peptides with Thianthrenium Salts: Conjugation and Ligation

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 62(9)

Published: Dec. 30, 2022

Abstract Bioorthogonal late‐stage diversification of structurally complex peptides bears enormous potential for drug discovery and molecular imaging, among other applications. Herein, we report on a palladium‐catalyzed C−H arylation tryptophan‐containing with readily accessible modular arylthianthrenium salts. Under exceedingly mild reaction conditions, the was accomplished. The tunability ease preparation salts allowed expedient stitching drug, natural product, peptidic scaffolds by forging sterically congested biaryl linkages. robustness palladium catalysis regime reflected full tolerance plethora sensitive coordinating functional groups. Hence, our manifold enabled efficient access to highly decorated, labelled, conjugated, ligated linear cyclic peptides.

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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Photocatalytic Functionalization of Dehydroalanine‐Derived Peptides in Batch and Flow

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(19)

Published: March 18, 2024

Abstract Unnatural amino acids, and their synthesis by the late‐stage functionalization (LSF) of peptides, play a crucial role in areas such as drug design discovery. Historically, LSF biomolecules has predominantly utilized traditional synthetic methodologies that exploit nucleophilic residues, cysteine, lysine or tyrosine. Herein, we present photocatalytic hydroarylation process targeting electrophilic residue dehydroalanine (Dha). This possesses an α , β ‐unsaturated moiety can be combined with various arylthianthrenium salts, both batch flow reactors. Notably, setup proved instrumental for efficient scale‐up, paving way unnatural acids peptides substantial quantities. Our approach, being inherently mild, permits diversification even when they contain sensitive functional groups. The readily available salts facilitate seamless integration Dha‐containing wide range arenes, blueprints, natural products, culminating creation unconventional phenylalanine derivatives. synergistic effect high group tolerance modular characteristic aryl electrophile enables peptide conjugation ligation conditions.

Language: Английский

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Empowering Molecule Discovery for Molecule-Caption Translation with Large Language Models: A ChatGPT Perspective

IEEE Transactions on Knowledge and Data Engineering, Journal Year: 2024, Volume and Issue: 36(11), P. 6071 - 6083

Published: May 2, 2024

Molecule discovery plays a crucial role in various scientific fields, advancing the design of tailored materials and drugs, which contributes to development society human well-being.Specifically, molecule-caption translation is an important task for molecule discovery, aligning understanding with molecular space.However, most existing methods heavily rely on domain experts, require excessive computational cost, or suffer from sub-optimal performance.On other hand, Large Language Models (LLMs), like ChatGPT, have shown remarkable performance cross-modal tasks due their powerful capabilities natural language understanding, generalization, in-context learning (ICL), provides unprecedented opportunities advance discovery.Despite several previous works trying apply LLMs this task, lack domain-specific corpus difficulties training specialized still remain challenges.In work, we propose novel LLM-based framework (MolReGPT) translation, where In-Context Few-Shot Learning paradigm introduced empower ChatGPT perform capability without pre-training fine-tuning.MolReGPT leverages principle similarity retrieve similar molecules text descriptions local database enable learn knowledge context examples.We evaluate effectiveness MolReGPT including text-based generation.Experimental results show that compared fine-tuned models, outperforms MolT5-base comparable MolT5-large additional training.To best our knowledge, first work leverage via discovery.Our expands scope LLM applications, as well providing new design.Notably, implementation available at: https://github.com/phenixace/

Language: Английский

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Recent Advances in Photoinduced Modification of Amino Acids, Peptides, and Proteins

The Chemical Record, Journal Year: 2024, Volume and Issue: 24(3)

Published: Jan. 26, 2024

Abstract The chemical modification of biopolymers like peptides and proteins is a key technology to access vaccines pharmaceuticals. Similarly, the tunable derivatization individual amino acids important as they are building blocks biomolecules, bioactive natural products, synthetic polymers, innovative materials. high diversity functional groups present in acid‐based molecules represents significant challenge for their selective Recently, visible light‐mediated transformations have emerged powerful strategy achieving chemoselective biomolecule modification. This technique offers numerous advantages over other methods, including higher selectivity, mild reaction conditions functional‐group tolerance. review provides an overview most recent methods covering photoinduced single site‐selective functionalization under even biocompatible conditions. Future challenges perspectives discussed beyond diverse types photocatalytic that currently available.

Language: Английский

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