Electrochemical Late-Stage Functionalization

Chemical Reviews, Год журнала: 2023, Номер 123(19), С. 11269 - 11335

Опубликована: Сен. 26, 2023

Late-stage functionalization (LSF) constitutes a powerful strategy for the assembly or diversification of novel molecular entities with improved physicochemical biological activities. LSF can thus greatly accelerate development medicinally relevant compounds, crop protecting agents, and functional materials. Electrochemical synthesis has emerged as an environmentally friendly platform transformation organic compounds. Over past decade, electrochemical late-stage (eLSF) gained major momentum, which is summarized herein up to February 2023.

Язык: Английский

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Electrochemical chemoselective thiocarbamylation of late-stage Tyr-containing drugs and peptides

Science China Chemistry, Год журнала: 2024, Номер 67(10), С. 3382 - 3388

Опубликована: Авг. 2, 2024

Язык: Английский

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Metal-free photocatalytic cross-electrophile coupling enables C1 homologation and alkylation of carboxylic acids with aldehydes

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

Опубликована: Фев. 19, 2024

In contemporary drug discovery, enhancing the sp

Язык: Английский

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Selenium chemistry for spatio-selective peptide and protein functionalization

Nature Reviews Chemistry, Год журнала: 2024, Номер 8(3), С. 211 - 229

Опубликована: Фев. 22, 2024

Язык: Английский

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Photocatalytic Functionalization of Dehydroalanine‐Derived Peptides in Batch and Flow

Angewandte Chemie International Edition, Год журнала: 2024, Номер 63(19)

Опубликована: Март 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.

Язык: Английский

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Selective Electrochemical Modification and Degradation of Polymers

Angewandte Chemie International Edition, Год журнала: 2024, Номер 63(20)

Опубликована: Фев. 28, 2024

Abstract We demonstrate that electrochemical‐induced decarboxylation enables reliable post‐polymerization modification and degradation of polymers. Polymers containing N ‐(acryloxy)phthalimides were subjected to electrochemical under mild conditions, which led the formation transient alkyl radicals. By installing these redox‐active units, we systematically modified pendent groups chain ends polyacrylates. This approach enabled production poly(ethylene‐ co ‐methyl acrylate) poly(propylene‐ copolymers, are difficult synthesize by direct polymerization. Spectroscopic chromatographic techniques reveal transformations near‐quantitative on several polymer systems. Electrochemical also all‐methacrylate poly( ‐(methacryloxy)phthalimide‐ methacrylate) copolymers with a efficiency >95 %. Chain cleavage is achieved through ‐hydroxyphthalimide ester subsequent β‐scission backbone radical. Electrochemistry thus shown be powerful tool in selective controlled macromolecular degradation.

Язык: Английский

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Cysteine‐Specific Multifaceted Bioconjugation of Peptides and Proteins Using 5‐Substituted 1,2,3‐Triazines

Advanced Science, Год журнала: 2024, Номер 11(21)

Опубликована: Март 11, 2024

Abstract Peptide and protein postmodification have gained significant attention due to their extensive impact on biomolecule engineering drug discovery, of which cysteine‐specific modification strategies are prominent inherent nucleophilicity low abundance. Herein, the study introduces a novel approach utilizing multifunctional 5‐substituted 1,2,3‐triazine derivatives achieve multifaceted bioconjugation targeting cysteine‐containing peptides proteins. On one hand, this represents an inaugural instance employing in biomolecular‐specific within physiological solution. other as powerful combination precision biorthogonality, strategy allows for one‐pot dual‐orthogonal functionalization biomolecules aldehyde group generated simultaneously. 1,2,3‐Triazine with diverse functional groups allow conjugation or proteins, while bi‐triazines enable peptide cyclization dimerization. The examination stability revealed potential reversible modification. This work establishes comprehensive platform identifying cysteine‐selective modifications, providing new avenues peptide‐based development, bioconjugation, chemical biology research.

Язык: Английский

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Late-Stage Peptide Modification and Macrocyclization Enabled by Tertiary Amine Catalyzed Tryptophan Allylation

Chemical Science, Год журнала: 2024, Номер 15(28), С. 11099 - 11107

Опубликована: Янв. 1, 2024

An unprecedented tertiary amine catalyzed peptide allylation between Trp and MBH carbonates was disclosed, to enable late-stage functionalization macrocyclization both in traditional homogeneous phase on-resins SPPS.

Язык: Английский

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Electrochemical synthesis of peptide aldehydes via C‒N bond cleavage of cyclic amines

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

Опубликована: Июнь 18, 2024

Abstract Peptide aldehydes are crucial biomolecules essential to various biological systems, driving a continuous demand for efficient synthesis methods. Herein, we develop metal-free, facile, and biocompatible strategy direct electrochemical of unnatural peptide aldehydes. This electro-oxidative approach enabled step- atom-economical ring-opening via C‒N bond cleavage, allowing homoproline-specific diversification expansion substrate scope include amides, esters, cyclic amines sizes. The remarkable efficacy the electro-synthetic protocol set stage modification assembly linear macrocyclic peptides using concise synthetic sequence with racemization-free conditions. Moreover, combination experiments density functional theory (DFT) calculations indicates that different N -acyl groups play decisive role in reaction activity.

Язык: Английский

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Non-symmetric stapling of native peptides

Nature Reviews Chemistry, Год журнала: 2024, Номер 8(5), С. 304 - 318

Опубликована: Апрель 4, 2024

Язык: Английский

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