Giese-type alkylation of dehydroalanine derivatives via silane-mediated alkyl bromide activation DOI Creative Commons

Perry van der Heide,

Michele Retini, Fabiola Fanini

et al.

Beilstein Journal of Organic Chemistry, Journal Year: 2024, Volume and Issue: 20, P. 3274 - 3280

Published: Dec. 17, 2024

The rising popularity of bioconjugate therapeutics has led to growing interest in late-stage functionalization (LSF) peptide scaffolds. α,β-Unsaturated amino acids like dehydroalanine (Dha) derivatives have emerged as particularly useful structures, the electron-deficient olefin moiety can engage reactions, a Giese-type reaction. Cheap and widely available building blocks organohalides be converted into alkyl radicals by means photoinduced silane-mediated halogen-atom transfer (XAT) offer mild straightforward methodology alkylation. In this research, we present metal-free strategy for photochemical alkylation derivatives. Upon abstraction hydride from tris(trimethylsilyl)silane (TTMS) an excited benzophenone derivative, formed silane radical undergo XAT with bromide generate radical. Consequently, undergoes reaction Dha forming new C(sp 3 )–C(sp ) bond. performed phosphate-buffered saline (PBS) solution shows post-functionalization prospects through pathways involving classical chemistry.

Language: Английский

Copper-Catalyzed Successive Radical Reactions of Glycine Derivatives DOI

Youwan Ye,

Dong-Sheng Ji,

Chenxing Zhou

et al.

Organic Letters, Journal Year: 2025, Volume and Issue: 27(4), P. 1054 - 1059

Published: Jan. 16, 2025

Here, we present a three-component successive radical addition strategy for the preparation of complex noncanonical α-amino acids from easily available glycine derivatives, alkenes, and aryl sulfonium salts via copper-catalyzed photoredox-neutral catalytic cycle. The utility this method is further demonstrated by its application in late-stage site-selective modifications residues short peptides. It worth noting that only 1 mol % copper catalyst required reaction, demonstrating high efficiency.

Language: Английский

Citations

1
Hydrodeuteroalkylation of Unactivated Olefins Using Thianthrenium Salts DOI
Jie Zhang,

Mengjie Jiao,

Zheng Lu

et al.

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(36)

Published: June 13, 2024

Isotopically labeled alkanes play a crucial role in organic and pharmaceutical chemistry. While some deuterated methylating agents are readily available, the limited accessibility of other deuteroalkyl reagents has hindered synthesis corresponding products. In this study, we introduce nickel-catalyzed system that facilitates various deuterium-labeled through hydrodeuteroalkylation d2-labeled alkyl TT salts with unactivated alkenes. Diverging from traditional reagents, thianthrenium (TT) can effectively selectively deuterium at α position chains using D

Language: Английский

Citations

6
Decyanative Heteroarylations of Glycine Derivatives DOI

Chenxing Zhou,

Dongsheng Ji, Xuxia Wang

et al.

Organic Letters, Journal Year: 2024, Volume and Issue: 26(25), P. 5323 - 5328

Published: June 17, 2024

Amino acids and aromatic nitrogen heterocycles are widely used in pharmaceuticals. Herein, we present an effective visible-light-driven thiobenzoic acid (TBA)-catalyzed decyanative C(sp3)–H heteroarylation of glycine derivatives. This process occurs under mild straightforward conditions, affording a range valuable yet challenging-to-obtain α-heteroaryl amino Moreover, this organocatalytic C(sp3)–C(sp2) bond formation reaction is applicable to the late-stage modification various short peptides.

Language: Английский

Citations

6
Radical-polar Crossover Reaction of Glycine Derivatives DOI

Youwan Ye,

Xin Zhang,

Peng Kong

et al.

Chemical Communications, Journal Year: 2024, Volume and Issue: 60(75), P. 10378 - 10381

Published: Jan. 1, 2024

Here we report a visible-light facilitated radical addition strategy for the preparation of various natural or unnatural α-amino acids from readily available glycine derivatives and alkenes. A key aspect in achieving this side carbon chain introduction reaction, while circumventing well-documented cyclization pathway, was employment radical-polar crossover under redox neutral conditions.

Language: Английский

Citations

5
Alkylation of Glycine Derivatives through a Synergistic Single-Electron Transfer and Halogen-Atom Transfer Process DOI

Peng Kong,

Youwan Ye,

Xin Zhang

et al.

Organic Letters, Journal Year: 2024, Volume and Issue: 26(36), P. 7507 - 7513

Published: Aug. 29, 2024

Here, we present a versatile method for forming C(sp

Language: Английский

Citations

4
Ligand-Enabled Selective Coupling of MIDA Boronates to Dehydroalanine-Containing Peptides and Proteins DOI
Alexander A. Vinogradov,

Shoe-Kung Pan,

Hiroaki Suga

et al.

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: 147(9), P. 7533 - 7544

Published: Feb. 21, 2025

α,β-dehydroalanine (ΔAla) is a uniquely reactive nonproteinogenic amino acid often employed for the late-stage functionalization of peptides, natural products (NPs), and proteins. The modification ΔAla powerful method semisynthetic engineering NPs post-translational protein mutagenesis. Numerous enabling techniques have been developed over years, but most state-of-the-art approaches furnish product mixtures detrimental in many applications. Here, we report Pd(II)-mediated coupling reaction between aryl N-methylimidodiacetic boronates ΔAla-containing peptides proteins which yields ΔzPhe with high selectivity. proceeds water under ambient conditions (37 °C, <24 h) without exclusion oxygen using fully unprotected substrates. speed selectivity enabled by use N,N'-ethylene-bis-Lthreonine as Pd(II) ligand. We utilize this chemistry to selectively functionalize variety oligopeptides, NP-like compounds, intact Finally, show that can be readily adapted modify vitro translated devising platform chemoribosomal synthesis ΔzPhe-containing structures. Altogether, our provides tool selective

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
Upscaled Synthesis of α‐ and β‐Peptides in a Continuous‐Flow Reactor Using Propylene Carbonate as an Eco‐Friendly Solvent DOI Open Access
Nikolett Varró,

Beáta Mándityné Huszka,

Eszter Erdei

et al.

Chemistry - Methods, Journal Year: 2025, Volume and Issue: unknown

Published: May 2, 2025

A rapid, eco‐friendly, and scalable continuous‐flow solid‐phase peptide synthesis (CF‐SPPS) technology has been developed using propylene carbonate (PC) as a solvent. PC, greener alternative to DMF, is selected based on the GSK solvent selection guide. To evaluate its compatibility with CF‐SPPS, four α‐peptides were synthesized, achieving high yields purity. The method further validated challenging sequences, including β‐peptide foldamers an α/β‐peptide chimera. scale up this innovative approach, larger column geometries are optimized ensure appropriate resin load flow rate for desired residence times. demonstrated capability synthesize peptides >4 g satisfactory efficiency. key feature use of PC in minimal amounts, significantly enhancing process's green credentials. low consumption efficiency align chemistry principles, reducing waste improving sustainability. process mass intensity highlights environmental benefits, making it sustainable large‐scale synthesis. This breakthrough showcases potential CF‐SPPS meet demands more efficient production.

Language: Английский

Citations

0
Late-Stage N-Arylation of Tryptophan-Containing Peptides and Drug Molecules via Arylthianthrenium Salts DOI
Haoxiang Zhang,

Huimin Dong,

Ye Wu

et al.

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

Published: May 15, 2025

We report herein a mild and efficient method for the late-stage N-arylation of tryptophan tryptophan-containing peptides using readily accessible arylthianthrenium salts through dual photoredox/copper catalysis. Applying this protocol, library noncanonical amino acids N-arylated was facilely prepared. Moreover, protocol enables peptide ligation conjugation, offering convenient access to ligated peptide/drug conjugates. Remarkably, strategy can also be applied modification complex drug molecules.

Language: Английский

Citations

0
Alkane functionalization: Recent advances DOI
Nuno Reis Conceição, Kamran T. Mahmudov⧫, M. Fátima C. Guedes da Silva

et al.

Coordination Chemistry Reviews, Journal Year: 2024, Volume and Issue: 522, P. 216175 - 216175

Published: Sept. 13, 2024

Language: Английский

Citations

2