Rh(III)-Catalyzed Double C–H Activation toward Peptide–Benzazepine Conjugates DOI

Qi Quan,

Yan Li,

Zhefan Zhang

et al.

Organic Letters, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 23, 2024

We herein report the efficient synthesis of peptide–benzazepine conjugates from Lys-based peptides and acroleins via Rh(III)-catalyzed double C–H activation. This reaction features mild conditions, broad scope, high atom step economies, excellent chemo- site selectivity. The synthetic utility this strategy is further demonstrated by scale-up experiments product derivatizations, including diverse late-stage ligations based on aldehyde moiety. preliminary biological activity studies show that have good antifungal activities toward crop forest pathogenic fungi.

Language: Английский

Transition-Metal-Catalyzed C–C Bond Macrocyclization via Intramolecular C–H Bond Activation DOI Open Access
Xiao Wang, Mingzhu Lu, Teck‐Peng Loh

et al.

Catalysts, Journal Year: 2023, Volume and Issue: 13(2), P. 438 - 438

Published: Feb. 17, 2023

Macrocycles are commonly synthesized via late-stage macrolactamization and macrolactonization. Strategies involving C–C bond macrocyclization have been reported, examples include the transition-metal-catalyzed ring-closing metathesis coupling reactions. In this mini-review, we summarize recent progress in direct synthesis of polyketide polypeptide macrocycles using a C–H activation strategy. first part, rhodium-catalyzed alkene–alkene for is described. The second part summarizes macrocycles. indolyl aryl C(sp2)–H bonds followed by with various partners such as halides, arylates, alkynyl bromide then documented. Moreover, reactions alkyl C(sp3)–H also included. We hope that mini-review will inspire more researchers to explore new broadly applicable strategies intramolecular activation.

Language: Английский

Citations

10
Late-stage peptide labeling with near-infrared fluorogenic nitrobenzodiazoles by manganese-catalyzed C–H activation DOI Creative Commons
Tsuyoshi Oyama, Lorena Mendive‐Tapia,

Verity Cowell

et al.

Chemical Science, Journal Year: 2023, Volume and Issue: 14(21), P. 5728 - 5733

Published: Jan. 1, 2023

Late-stage diversification of structurally complex amino acids and peptides provides tremendous potential for drug discovery molecular imaging. Specifically, labeling with fluorescent tags is one the most important methods visualizing their mode operation. Despite major recent advances in field, direct peptide by C-H activation largely limited to dyes relatively short emission wavelengths, leading high background signals poor signal-to-noise ratios. In sharp contrast, here we report on catalyzed non-toxic manganese(i) via C(sp2)-H alkenylation chemo- site-selective manners, providing modular access novel near-infrared (NIR) nitrobenzodiazole-based fluorogenic probes.

Language: Английский

Citations

10
Site-Selective Modification of Peptides via Late-Stage Pd-Catalyzed Tandem Reaction of Phenylalanine with Benzoquinone DOI
Jian Tang,

Fengjie Lu,

Yujie Geng

et al.

Organic Letters, Journal Year: 2023, Volume and Issue: 25(28), P. 5378 - 5382

Published: July 13, 2023

An efficient and straightforward approach for site-selective functionalization of phenylalanine phenylalanine-containing peptide via a Pd-catalyzed tandem reaction has been developed. The robust method underwent dual C–H activation, including C–C coupling with benzoquinone intramolecular C–N cyclization, providing feasible rapid synthetic route to incorporate 4-benzoquinone-indoline fragments into peptides.

Language: Английский

Citations

10
Synthesis of Fluorescent Cyclic Peptides via Gold(I)-Catalyzed Macrocyclization DOI Creative Commons

Xingyu Liu,

Wei Cai, Nathan Ronceray

et al.

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(49), P. 26525 - 26531

Published: Nov. 30, 2023

Rapid and efficient cyclization methods that form structurally novel peptidic macrocycles are of high importance for medicinal chemistry. Herein, we report the first gold(I)-catalyzed macrocyclization peptide-EBXs (ethynylbenziodoxolones) via C2-Trp C–H activation. This reaction was carried out in presence protecting group free peptide sequences is enabled by a simple commercial gold catalyst (AuCl·Me2S). The method displayed rapid rate (within 10 min), wide functional tolerance (27 unprotected peptides were cyclized), up to 86% isolated yield. obtained highly conjugated cyclic linker, formed through alkynylation, can be directly applied live-cell imaging as fluorescent probe without further attachment fluorophores.

Language: Английский

Citations

10
Late-Stage Stitching Enabled by Palladium-Catalyzed Tryptophan C4 Amination: Peptide Ligation and Cyclodimerization DOI
Yazhou Li, Yu Zhang, Tao Yu

et al.

Organic Letters, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 11, 2025

Here, we report on methods for late-stage peptide diversification through palladium-catalyzed site-selective C(sp2)–H amination of tryptophan residues at the C4 position, utilizing tryptophan-amine cross-links. Our strategy enables practical access to C–N bonds, facilitating construction cyclopeptides via cyclodimerization structurally complex peptides, which poses significant challenges organic synthesis. The synthetic utility this protocol is demonstrated synthesis 30- 38-membered macrocyclic peptides.

Language: Английский

Citations

0
Post-synthetic Chemical Functionalization of Peptides DOI

Stephanie A. Barros,

Rosaura Padilla‐Salinas, Irini Abdiaj

et al.

Elsevier eBooks, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

0
Pyridyloxy-Directed, Pd(II)-Catalyzed Late-Stage C(sp2)–H Alkynylation and Olefination of Tyrosine Oligopeptides DOI

Qing-Sheng Zhao,

Shu Shu Yang,

Tingting Guo

et al.

The Journal of Organic Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: May 19, 2025

Peptides and peptidomimetics have gained increasing interest as therapeutics due to their unique properties small molecules proteins. Herein, we report the pyridyloxy-directed Pd (II)-catalyzed C(sp2)-H alkynylation olefination of tyrosine residues in peptides with high chemo- site-selectivity. This method achieved functionalization at any position amino acid for olefination. Furthermore, this approach can be used synthesize peptide-biomolecule conjugates.

Language: Английский

Citations

0
Exploring Chemical Modifications of Aromatic Amino Acid Residues in Peptides DOI
Bishwajit Paul, Modhu Sudan Maji,

Susanta Bhunia

et al.

Synthesis, Journal Year: 2023, Volume and Issue: 55(22), P. 3701 - 3724

Published: May 11, 2023

Abstract The chemical diversification of biomolecules set forth a significant area research that constitutes an important intersection between chemistry and biology. Amino acids peptides are the fundamental building blocks proteins play essential roles in all living organisms. While efforts have been geared toward modification amino acid residues, particularly functionalization reactive functional groups such as lysine NH2 cysteine SH, exploration aromatic residues tryptophan, tyrosine, phenylalanine, histidine has relatively limited. Therefore, this review highlights strategies for side-chain these four peptides, with focus on elucidating underlying mechanisms. We also illustrated use modifications biological realm. 1 Introduction 2 Tryptophan Modifications 3 Tyrosine 4 Phenylalanine 5 Histidine 6 Perspectives Future Outlook

Language: Английский

Citations

9
Ligand‐Enabled Pd‐Catalyzed sp3 C−H Macrocyclization: Synthesis and Evaluation of Macrocyclic Sulfonamide for the Treatment of Parkinson's Disease DOI Open Access

Tongyu Bi,

Yunxia Cui, Shuai Liu

et al.

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(45)

Published: July 30, 2024

Abstract The development of simplified synthetic strategy to create structurally and functionally diverse pseudo‐natural macrocyclic molecules is highly appealing but poses a marked challenge. Inspired by natural scaffolds, herein, we describe practical concise ligand‐enabled Pd(II)‐catalyzed sp 3 C−H alkylation, olefination arylation macrocyclization, which could offer novel set sulfonamides. Interestingly, the potential ligand acceleration in activation also demonstrated an unprecedented enantioselective alkylation macrocyclization. Moreover, combination silico screening biological evaluation led identification spiro‐grafted sulfonamide 2 , showed promising efficacy for treatment Parkinson's disease (PD) mouse model through silent information regulator sirtuin (SIRT3).

Language: Английский

Citations

3
Synthesis of maleimide-braced peptide macrocycles and their potential anti-SARS-CoV-2 mechanisms DOI
Jian Li,

Jina Sun,

Xianglei Zhang

et al.

Chemical Communications, Journal Year: 2022, Volume and Issue: 59(7), P. 868 - 871

Published: Dec. 12, 2022

Macrocycles often exhibit good biological properties and potential druggability, which lead to versatile applications in the pharmaceutical industry. Herein, we report a highly efficient practical methodology for functionalization macrocyclization of Trp Trp-containing peptides via Pd(II)-catalyzed C-H alkenylation at C4 position. This method provides direct access maleimide-decorated peptidomimetics maleimide-braced 17- 30-membered peptide macrocycles. In particular, these unique macrocycles revealed low micro- sub-micromolar EC50 values with promising anti-SARS-CoV-2 activities. Further explorations computational methodologies experimental validations indicated that exert antiviral effects through binding N protein SARS-CoV-2.

Language: Английский

Citations

13