Late-Stage Functionalization and Diversification of Peptides by Internal Thiazole-Enabled Palladium-Catalyzed C(sp3)–H Arylation DOI

Zengbing Bai,

Qingqing Chen, Jun Gu

et al.

ACS Catalysis, Journal Year: 2021, Volume and Issue: 11(24), P. 15125 - 15134

Published: Dec. 4, 2021

Modification of peptides via late-stage C–H activation is an emerging strategy to construct bioactive peptidomimetic libraries with expanded structural diversity for drug discovery. Peptides thiazole motifs in the backbone as amide surrogates often exhibit improved bioactivity and biostability. However, methods synthesize this class compounds are limited. Here, we report development a highly versatile palladium-catalyzed C(sp3)–H arylation peptides. This protocol utilizes peptide internal directing groups allows regio- site-selective β-C(sp3)–H γ-C(sp3)–H bonds side chains. The high biocompatibility method functionalize ligate variety aryl donors, biomolecules, fluorophores sets stage efficient construction featured units.

Language: Английский

C–H activation DOI
Torben Rogge, Nikolaos Kaplaneris, Naoto Chatani

et al.

Nature Reviews Methods Primers, Journal Year: 2021, Volume and Issue: 1(1)

Published: June 17, 2021

Language: Английский

Citations

435
Transition-Metal-Catalyzed C–H Bond Activation for the Formation of C–C Bonds in Complex Molecules DOI Creative Commons
Jamie H. Docherty,

Thomas M. Lister,

Gillian McArthur

et al.

Chemical Reviews, Journal Year: 2023, Volume and Issue: 123(12), P. 7692 - 7760

Published: May 10, 2023

Site-predictable and chemoselective C–H bond functionalization reactions offer synthetically powerful strategies for the step-economic diversification of both feedstock fine chemicals. Many transition-metal-catalyzed methods have emerged selective activation bonds. However, challenges regio- chemoselectivity with application to highly complex molecules bearing significant functional group density diversity. As molecular complexity increases within structures risks catalyst intolerance limited applicability grow number groups potentially Lewis basic heteroatoms. Given abundance bonds already diversified such as pharmaceuticals, natural products, materials, design selection reaction conditions tolerant catalysts has proved critical successful direct functionalization. such, innovations formation carbon–carbon been discovered developed overcome these limitations. This review highlights progress made metal-catalyzed C–C forming including alkylation, methylation, arylation, olefination targets.

Language: Английский

Citations

228
Recent Advances in Alkenyl sp2 C–H and C–F Bond Functionalizations: Scope, Mechanism, and Applications DOI
Mingzhu Lu, Jeffrey Goh, Manikantha Maraswami

et al.

Chemical Reviews, Journal Year: 2022, Volume and Issue: 122(24), P. 17479 - 17646

Published: Oct. 14, 2022

Alkenes and their derivatives are featured widely in a variety of natural products, pharmaceuticals, advanced materials. Significant efforts have been made toward the development new practical methods to access this important class compounds by selectively activating alkenyl C(sp2)–H bonds recent years. In comprehensive review, we describe state-of-the-art strategies for direct functionalization sp2 C–H C–F until June 2022. Moreover, metal-free, photoredox, electrochemical also covered. For clarity, review has divided into two parts; first part focuses on currently available using different alkene as starting materials, second describes bond easily accessible gem-difluoroalkenes material. This includes scope, limitations, mechanistic studies, stereoselective control (using directing groups well metal-migration strategies), applications complex molecule synthesis where appropriate. Overall, aims document considerable advancements, current status, emerging work critically summarizing contributions researchers working fascinating area is expected stimulate novel, innovative, broadly applicable functionalizations coming

Language: Английский

Citations

150
Recent advances in transition metal-catalyzed olefinic C–H functionalization DOI
Bingxian Liu, Lingyun Yang, Pengfei Li

et al.

Organic Chemistry Frontiers, Journal Year: 2020, Volume and Issue: 8(5), P. 1085 - 1101

Published: Dec. 23, 2020

Recent advances during 2015–2020 in the field of metal-catalyzed olefinic C–H functionalization are organized according to metal center catalyst, with an emphasis on similarities and differences among different catalysts.

Language: Английский

Citations

144
Decoding Directing Groups and Their Pivotal Role in C−H Activation DOI
Karunanidhi Murali, Luana A. Machado, Renato L. Carvalho

et al.

Chemistry - A European Journal, Journal Year: 2021, Volume and Issue: 27(49), P. 12453 - 12508

Published: May 26, 2021

Synthetic organic chemistry has witnessed a plethora of functionalization and defunctionalization strategies. In this regard, C-H been at the forefront due to multifarious applications in development simple complex molecular architectures holds brilliant prospect drug discovery. Despite explored tremendously by chemists, strategy still enjoys employment novel metal catalysts as well metal-free ligands. Moreover, switch photo- electrochemistry widened our understanding alternative pathways via which reaction can proceed these strategies have garnered prominence when applied activation. chemists foraging for new directing groups templates selective activation bonds from myriad carbon-hydrogen aromatic aliphatic systems. As matter fact, varying groups, scientists found answer challenge distal bond remained an obstacle very long time. These frequently harnessed selectively activating natural products, drugs, macromolecules decorated with multiple bonds. This itself was before commencement field site other than targeted could modify hamper biological activity pharmacophore. Total synthesis pharmacophore often faces difficulty superfluous steps towards functionalization. solved late-stage simply harnessing green conditions seen light past few decades rising concern about environmental issues. Therefore, or usage non-toxic metals recently showcased number elegant works. Also, research across world are developing rational group free non-directed protocols that just guided review encapsulates works pertinent discusses science devoted it fundamental level. gives readers broad how work, execution various catalysts, groups. not only helps budding scientist his/her but also matured mind searching out A detailed picture its progress time portrayed lucid scientific language motive inculcate educate minds beautiful overview most relevant significant era. The unique trait is description classification their utility over wide substrate scope. allows experimental chemist understand applicability domain employ any substrate.

Language: Английский

Citations

97
Reactivity-Controlling Factors in Carboxylate-Assisted C–H Activation under 4d and 3d Transition Metal Catalysis DOI
Torben Rogge, João C. A. Oliveira, Rositha Kuniyil

et al.

ACS Catalysis, Journal Year: 2020, Volume and Issue: 10(18), P. 10551 - 10558

Published: Aug. 17, 2020

Detailed density functional theory calculations provide valuable insight into reactivity-controlling factors in transition metal-catalyzed C–H activation by carboxylate assistance. The chelation-assisted of a variety arenes 3d and 4d metal complexes was analyzed means bond order analysis through (DFT) as well energy decomposition DLPNO–CCSD(T) calculations, thereby providing in-depth information on distinct electronic influences the key state demonstrating preferred base-assisted internal electrophilic substitution (BIES) rather than concerted metalation-deprotonation (CMD) pathway.

Language: Английский

Citations

93
The emergence of the C–H functionalization strategy in medicinal chemistry and drug discovery DOI
Ranjan Jana, Hasina Mamataj Begam,

Enakshi Dinda

et al.

Chemical Communications, Journal Year: 2021, Volume and Issue: 57(83), P. 10842 - 10866

Published: Jan. 1, 2021

Owing to the market competitiveness and urgent societal need, an optimum speed of drug discovery is important criterion for successful implementation. Despite rapid ascent artificial intelligence computational bioanalytical techniques accelerate in big pharma, organic synthesis privileged scaffolds predicted silico vitro vivo studies still considered as rate-limiting step. C-H activation latest technology added into chemist's toolbox construction late-stage modification functional molecules achieve desired chemical physical properties. Particularly, elimination prefunctionalization steps, exceptional group tolerance, complexity-to-diversity oriented synthesis, functionalization medicinal expand space. It has immense potential a library molecules, structural required pharmacological properties such absorption, distribution, metabolism, excretion, toxicology (ADMET) attachment reporters proteome profiling, metabolite etc. preclinical studies. Although heterocycle modification, 18F labelling, methylation, via have been reviewed from synthetic standpoint, general overview these protocols aspects not reviewed. In this feature article, we will discuss recent trends methodologies through activation/annulation cascade; arylation sp2-sp2 sp2-sp3 cross-coupling; borylation/silylation introduce linchpin further manipulation; amination N-heterocycles hydrogen bond acceptors; fluorination/fluoroalkylation tune polarity lipophilicity; methylation: methyl magic discovery; peptide macrocyclization therapeutics biologics; fluorescent labelling radiolabelling bioimaging; bioconjugation biology studies; drug-metabolite biodistribution excretion diversification drug-molecules increase efficacy safety; cutting-edge DNA encoded improved chemistry discovery.

Language: Английский

Citations

92
Directed Evolution of a Modular Polyketide Synthase Thioesterase for Generation of a Hybrid Macrocyclic Ring System DOI
Maria L. Adrover‐Castellano, Brian J. Curtis,

Jennifer J. Schmidt

et al.

ACS Catalysis, Journal Year: 2025, Volume and Issue: unknown, P. 3405 - 3417

Published: Feb. 11, 2025

Language: Английский

Citations

1
Diastereoselective palladium-catalyzed functionalization of prochiral C(sp3)–H bonds of aliphatic and alicyclic compounds DOI
Srinivasarao Arulananda Babu,

Yashika Aggarwal,

Pooja Patel

et al.

Chemical Communications, Journal Year: 2022, Volume and Issue: 58(16), P. 2612 - 2633

Published: Jan. 1, 2022

Advancements in the palladium-catalyzed functionalization of diastereotopic or prochiral C(sp 3 )–H bonds generating stereogenic centers and stereo-arrays aliphatic compounds have been highlighted.

Language: Английский

Citations

33
PIII‐Directed Late‐Stage Ligation and Macrocyclization of Peptides with Olefins by Rhodium Catalysis DOI
Lei Liu,

Xinlong Fan,

Boning Wang

et al.

Angewandte Chemie International Edition, Journal Year: 2022, Volume and Issue: 61(31)

Published: May 23, 2022

Transition metal-catalyzed C-H activation is a step-economical strategy for peptide functionalization. Herein, we report the method of late-stage ligation and macrocyclization through rhodium-catalyzed alkylation tryptophan residues at C7 position. This utilizes N-Pt Bu2 directing group tolerates various alkene substrates. Utilizing internal olefins, this study represents first example site-selective deconjugative isomerization. Furthermore, our provides access to macrocycles with unique Trp(C7)-alkyl crosslinks potent cytotoxicity towards cancer cells.

Language: Английский

Citations

27