Copper(I)-Catalyzed Late-Stage Introduction of Oxime Ethers into Peptides at the Carboxylic Acid Site

Liu, Yuyang; He, Zeyuan; Ma, Wen; Bao, Guangjun; Li, Yiping; Yu, Changjun; Li, Jingyue; Ruiyao, E; Xu, Zhaoqing; Wang, Rui; Sun, Wangsheng

doi:10.1021/acs.orglett.2c03813

Cited by 14 publications

(5 citation statements)

References 64 publications

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“…Isoxazoles with a heteroatom substituent at C5 have found wide application as convenient precursors of 2H-azirine-2-carboxylic acid derivatives, versatile building blocks for organic synthesis [31]. A very large number of structurally diverse azirines have been synthesized to date, including those which are of interest for biorthogonal chemistry [32], the chemistry of natural compounds [33], and medicine [34], but azirines with acridinyl substituents are still unknown in the literature.…”

Section: Resultsmentioning

confidence: 99%

Acridine–Isoxazole and Acridine–Azirine Hybrids: Synthesis, Photochemical Transformations in the UV/Visible Radiation Boundary Region, and Anticancer Activity

Galenko,

Novikov,

Bunev

et al. 2024

Molecules

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Easy-to-handle N-hydroxyacridinecarbimidoyl chloride hydrochlorides were synthesized as convenient nitrile oxide precursors in the preparation of 3-(acridin-9/2-yl)isoxazole derivatives via 1,3-dipolar cycloaddition with terminal alkynes, 1,1-dichloroethene, and acrylonitrile. Azirines with an acridin-9/2-yl substituent attached directly or via the 1,2,3-triazole linker to the azirine C2 were also synthesized. The three-membered rings of the acridine–azirine hybrids were found to be resistant to irradiation in the UV/visible boundary region, despite their long-wave absorption at 320–420 nm, indicating that the acridine moiety cannot be used as an antenna to transfer light energy to generate nitrile ylides from azirines for photoclick cycloaddition. The acridine–isoxazole hybrids linked at the C9–C3 or C2–C3 atoms under blue light irradiation underwent the addition of such hydrogen donor solvents, such as, toluene, o-xylene, mesitylene, 4-chlorotoluene, THF, 1,4-dioxane, or methyl tert-butyl ether (MTBE), to the acridine system to give the corresponding 9-substituted acridanes in good yields. The synthesized acridine–azirine, acridine–isoxazole, and acridane–isoxazole hybrids exhibited cytotoxicity toward both all tested cancer cell lines (HCT 116, MCF7, and A704) and normal cells (WI-26 VA4).

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Section: Resultsmentioning

confidence: 99%

Acridine–Isoxazole and Acridine–Azirine Hybrids: Synthesis, Photochemical Transformations in the UV/Visible Radiation Boundary Region, and Anticancer Activity

Galenko,

Novikov,

Bunev

et al. 2024

Molecules

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“…In this field, Sun et al [155] reported copper(I)-catalyzed vinyl nitrene-mediated late stage modification and functionalization of peptides through the reaction of N-alkoxylpeptidylamides and 2H-azirines (Scheme 99). N-alkoxylpeptidylamides can be pre-synthesized from amino acids and hydroxylamine.…”

Section: Ring-opening Of 2h-azirines To Acyclic Compoundsmentioning

confidence: 99%

2H‐Azirines: Recent Progress in Synthesis and Applications

Xu,

Zeng,

Luo

et al. 2024

Eur J Org Chem

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2H‐arizines are important three‐membered heterocycles in organic chemistry. Recently, many advances in the synthesis and functionalization of 2H‐arizines have been reported. Neber rearrangement, isomerization of isoxazole, oxidation of enamine, C–H bond activation, decomposition of vinyl azide, functionalization of alkyne, and multi‐step synthesis have been developed for the efficient assembly of 2H‐azirines. As versatile and highly strained three‐membered unsaturated heterocycles, 2H‐azirines can be used as distinctive building blocks towards significant functional groups, and have attracted extensive attention for the fabrication of numerous heterocycles. Recent studies have focused on [3+n] ring‐expansion reactions, nucleophilic addition of C=N double bond or continuous nucleophilic addition followed by cyclization, ring‐opening of 2H‐azirines to acyclic compounds, and substitution of sp3‐C‐H of 2H‐azirines. One of the most critical challenges is seeking for a selective opening of the specific three bonds of the strained azirine circle, some of what can be achieved on the basis of metal catalyst, photocatalysis, or combination of metal catalyst and photocatalysis. In this review, recent advances involving the synthesis and reactivity of 2H‐arizines accompanied with challenges and breakthroughs are summarized. The review mainly covers the period from 2019 to 2023.

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“…In line with our ongoing interest in peptide chemistry, including those Trp modications, 33,39,42,[45][46][47][48][49] we have been trying to explore more mild, easy-to-manipulate alternatives for peptide modication/functionalization to enrich the scenario. Promoted by our previous work on organocatalytic indole functionalization 50,51 and Morita-Baylis-Hillman (MBH) carbonate based allylation, [52][53][54] and inspired by Chen's N-allylic alkylation of indoles with MBH carbonates, 55 we sought to explore the reaction between Trp and MBH carbonates to develop a novel strategy for peptide functionalization.…”

Section: Introductionmentioning

confidence: 99%

Late-stage peptide modification and macrocyclization enabled by tertiary amine catalyzed tryptophan allylation

Liu,

Li,

et al. 2024

Chem. Sci.

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Copper(I)-Catalyzed Late-Stage Introduction of Oxime Ethers into Peptides at the Carboxylic Acid Site

Cited by 14 publications

References 64 publications

Acridine–Isoxazole and Acridine–Azirine Hybrids: Synthesis, Photochemical Transformations in the UV/Visible Radiation Boundary Region, and Anticancer Activity

Acridine–Isoxazole and Acridine–Azirine Hybrids: Synthesis, Photochemical Transformations in the UV/Visible Radiation Boundary Region, and Anticancer Activity

2H‐Azirines: Recent Progress in Synthesis and Applications

Late-stage peptide modification and macrocyclization enabled by tertiary amine catalyzed tryptophan allylation

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