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–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

233
Recent advances in chemical protein synthesis: method developments and biological applications DOI
Suwei Dong, Ji‐Shen Zheng, Yiming Li

et al.

Science China Chemistry, Journal Year: 2024, Volume and Issue: 67(4), P. 1060 - 1096

Published: March 12, 2024

Language: Английский

Citations

65
Tryptophan-specific modification and diversification of peptides and proteins DOI
S K Kundu, A. Bandyopadhyay, Rajib Sarkar

et al.

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

Citations

2
Functional and Promiscuity Studies of Three-Residue Cyclophane Forming Enzymes Show Nonnative C–C Cross-Linked Products and Leader-Dependent Cyclization DOI
Angelica Faith L. Suarez, Thi Quynh Ngoc Nguyen,

Litao Chang

et al.

ACS Chemical Biology, Journal Year: 2024, Volume and Issue: 19(3), P. 774 - 783

Published: Feb. 28, 2024

Enzymes catalyzing peptide macrocyclization are important biochemical tools in drug discovery. The three-residue cyclophane-forming enzymes (3-CyFEs) an emerging family of post-translational modifying that catalyze the formation cyclophanes. In this report, we introduce three additional 3-CyFEs, including ChlB, WnsB, and FnnB, cyclophane on Tyr, Trp, Phe, respectively. To understand promiscuity these those previously reported (MscB, HaaB, YxdB), tested single amino acid substitutions at motif modification (Ω1X2X3, Ω1 = aromatic). Collectively, observe substrate is observed X2 positions, but a greater specificity for X3 residue. Two nonnative products were characterized showing Phe-C3 to Arg-Cβ His-C2 Pro-Cβ cross-links, We also leader dependence selected 3-CyFEs show predicted helix region formation. These results demonstrate biocatalytic potential maturases allow rational design substrates obtain diverse array genetically encoded 3-residue

Language: Английский

Citations

10
Late-Stage Peptide Modification and Macrocyclization Enabled by Tertiary Amine Catalyzed Tryptophan Allylation DOI Creative Commons
Yuyang Liu, Guofeng Li, Wen Ma

et al.

Chemical Science, Journal Year: 2024, Volume and Issue: 15(28), P. 11099 - 11107

Published: Jan. 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.

Language: Английский

Citations

10
Backbone-enabled modification of peptides with benzoquinone via palladium-catalyzed δ-C(sp2)–H functionalization DOI

Fengjie Lu,

Yi Sun, Yaning Liu

et al.

Chemical Communications, Journal Year: 2024, Volume and Issue: 60(13), P. 1754 - 1757

Published: Jan. 1, 2024

Backbone-enabled site-selective modification of peptides with benzoquinone via Pd-catalyzed δ-C(sp 2 )–H functionalization has been achieved.

Language: Английский

Citations

7
Modular synthesis of clickable peptides via late-stage maleimidation on C(7)-H tryptophan DOI Creative Commons
Peng Wang, Jiang Liu, Xin-yun Zhu

et al.

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: July 5, 2023

Abstract Cyclic peptides have attracted tremendous attention in the pharmaceutical industry owing to their excellent cell penetrability, stability, thermostability, and drug-like properties. However, currently available facile methodologies for creating such are rather limited. Herein, we report an efficient direct peptide cyclization via rhodium(III)-catalyzed C(7)-H maleimidation. Notably, this catalytical system has regioselectivity high tolerance of functional groups which enable late-stage peptides. This architecture cyclic exhibits higher bioactivity than its parent linear Moreover, Trp-substituted maleimide displays reactivity toward Michael addition, indicating potential as a click group applications chemical biology medicinal chemistry. As proof principle, RGD-GFLG-DOX, is peptide-drug-conjugate, constructed it strong binding affinity antiproliferative activity integrin-αvβ 3 overexpressed cancer lines. The proposed strategy rapid preparation stapled would be robust tool peptide-drug conjugates.

Language: Английский

Citations

16
Metal-Free Late-Stage Alkylation of Tryptophan and Tryptophan-Containing Peptides with 1,3-Dithiane Derivatives DOI

Mingming Mao,

Jia Li,

Kang Dong

et al.

Organic Letters, Journal Year: 2023, Volume and Issue: 25(31), P. 5784 - 5789

Published: July 28, 2023

Late-stage diversification of structurally complex peptides has enormous potential for drug discovery and molecular imaging. We report a simple, metal-free, late-stage reductive C2 alkylation tryptophan tryptophan-containing using readily available 1,3-dithianes. This protocol wide substrate scope an excellent tolerance reactive functional groups.

Language: Английский

Citations

11
A multicomponent reaction for modular assembly of indole-fused heterocycles DOI Creative Commons
Jiaming Li, Hao Ni, Weiwei Zhang

et al.

Chemical Science, Journal Year: 2024, Volume and Issue: 15(14), P. 5211 - 5217

Published: Jan. 1, 2024

Indoles are privileged chemical entities in natural products and drug discovery. Indole-fused heterocycles, particularly seven-membered ones, have received increasing attention due to their distinctive characteristics wide spectrum of bioactivities. However, the synthetic access these compounds is highly limited. Herein, we report a unique multicomponent reaction (MCR) for modular assembly indole-fused heterocycles. In this process, indole, formaldehyde amino hydrochloride could assemble rapidly yield oxadiazepines, another addition sodium thiosulphate would furnish thiadiazepines. The biological evaluation disclosed promising anticancer activity compounds. Furthermore, MCR be applicable late-stage selective modifications peptides. Therefore, work provides powerful strategy indole functionalization valuable tool construction

Language: Английский

Citations

4
Macrocyclization of Maleimide-Decorated Peptides via Late-Stage Rh(III)-Catalyzed Trp(C7) Alkenylation DOI
Yu Zhang,

Shulei Hu,

Yazhou Li

et al.

Organic Letters, Journal Year: 2023, Volume and Issue: 25(14), P. 2456 - 2460

Published: March 31, 2023

Here, we report a novel strategy for constructing maleimide-containing peptides and cyclic using Rh(III)-catalyzed tryptophan (Trp) (C7) alkenylation, which is challenging due to the inherent reactivity of indole benzenoid ring. This method scalable exhibits broad substrate scope. The utility this protocol could further be demonstrated by synthesis peptide conjugates with natural products amino acids as well construction maleimide-braced peptides.

Language: Английский

Citations

11