Kanghui Song , Yuying Zhang , Shuai Wu , Sha Yang , Shengchen Wei , Songhua Chen , Hideto Ito , Kenichiro Itami , Yuanming Li
Employing spirophenanthrenes and phenanthrenone as template arenes for annulative π-extension (APEX), we synthesized a series of spiro-fused dibenzo[g,p]chrysenes (DBCs) in high yields. Experimental and theoretical investigations highlight the distinct advantages of spiro-DBCs, including characteristic fluorescence properties (412 nm) and enhanced thermal stability. This study provides insights into the electronic structure and potential applications of spiro-DBCs in organic functional materials.
{"title":"Spiro-fused dibenzo[g,p]chrysene: annulative π-extension (APEX) synthesis and properties†","authors":"Kanghui Song , Yuying Zhang , Shuai Wu , Sha Yang , Shengchen Wei , Songhua Chen , Hideto Ito , Kenichiro Itami , Yuanming Li","doi":"10.1039/d4qo02104e","DOIUrl":"10.1039/d4qo02104e","url":null,"abstract":"<div><div>Employing spirophenanthrenes and phenanthrenone as template arenes for annulative π-extension (APEX), we synthesized a series of spiro-fused dibenzo[<em>g</em>,<em>p</em>]chrysenes (DBCs) in high yields. Experimental and theoretical investigations highlight the distinct advantages of spiro-DBCs, including characteristic fluorescence properties (412 nm) and enhanced thermal stability. This study provides insights into the electronic structure and potential applications of spiro-DBCs in organic functional materials.</div></div>","PeriodicalId":94379,"journal":{"name":"Organic chemistry frontiers : an international journal of organic chemistry","volume":"12 7","pages":"Pages 2225-2231"},"PeriodicalIF":0.0,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143055565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The development of an advisable strategy to obtain biologically relevant polysubstituted furans and pyrroles is a highly anticipated yet challenging task. Here we report an efficient synthetic strategy for the rapid construction of multisubstituted C2-furan or pyrrole carboxylic acid derivatives via a cascade reaction from simple and readily available starting materials. This catalytic protocol, characterized by inexpensive Lewis catalysts and high atom economy, provides access to a wide variety of tri-, and tetrasubstituted furan/pyrrole derivatives in excellent yields. Gram-scale synthesis and synthetic applications are demonstrated.
{"title":"Lewis acid-catalyzed divergent synthesis of polysubstituted furans and pyrroles†","authors":"Chenguang Li , Tongxiang Cao , Shifa Zhu","doi":"10.1039/d4qo02216e","DOIUrl":"10.1039/d4qo02216e","url":null,"abstract":"<div><div>The development of an advisable strategy to obtain biologically relevant polysubstituted furans and pyrroles is a highly anticipated yet challenging task. Here we report an efficient synthetic strategy for the rapid construction of multisubstituted C2-furan or pyrrole carboxylic acid derivatives <em>via</em> a cascade reaction from simple and readily available starting materials. This catalytic protocol, characterized by inexpensive Lewis catalysts and high atom economy, provides access to a wide variety of tri-, and tetrasubstituted furan/pyrrole derivatives in excellent yields. Gram-scale synthesis and synthetic applications are demonstrated.</div></div>","PeriodicalId":94379,"journal":{"name":"Organic chemistry frontiers : an international journal of organic chemistry","volume":"12 7","pages":"Pages 2173-2179"},"PeriodicalIF":0.0,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143055569","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ya-Li Hu , Ding Dong , Jian-Jun Zhao , Kun Hu , Ling-Mei Kong , Yun-Xia Hu , Xing-Ren Li , Song-Yu Li , Yin Nian , Gang Xu
Ascynols A–C (), three polycyclic polyprenylated acylphloroglucinol (PPAP) derivatives sharing an unusual cyclopentane core, were isolated from the aerial parts of Hypericum ascyron L. Compounds and were elucidated to possess two novel 6/6/5/5 and 5/5 architectures, respectively. Additionally, twenty-four analogues () were also obtained, among which fourteen are new compounds. These compounds represent 11 different structural types and can be categorized into 6 groups based on their biosynthetic origin. Their structures were determined from spectroscopic analysis, quantum chemical calculation, and X-ray diffraction data. All the isolates are decorated with a methyl group at C-5 instead of a prenyl or geranyl group as in most other PPAPs. Biologically, sixteen compounds were identified as potent inhibitors of low-voltage-gated calcium channels (LVGCCs; Cav3.1–3.3), with IC50 values ranging from 1.89 to 16.55 μmol L−1. Moreover, compound exhibited strong and dose-dependent antinociception in an acetic acid-induced mouse model of visceral pain and its effect is comparable to that of Z944, a representative LVGCC inhibitor under clinical trial.
{"title":"5-Methylated polyprenylated acylphloroglucinol derivatives as low-voltage-gated Ca2+ channel inhibitors†","authors":"Ya-Li Hu , Ding Dong , Jian-Jun Zhao , Kun Hu , Ling-Mei Kong , Yun-Xia Hu , Xing-Ren Li , Song-Yu Li , Yin Nian , Gang Xu","doi":"10.1039/d4qo02233e","DOIUrl":"10.1039/d4qo02233e","url":null,"abstract":"<div><div>Ascynols A–C (), three polycyclic polyprenylated acylphloroglucinol (PPAP) derivatives sharing an unusual cyclopentane core, were isolated from the aerial parts of <em>Hypericum ascyron</em> L. Compounds and were elucidated to possess two novel 6/6/5/5 and 5/5 architectures, respectively. Additionally, twenty-four analogues () were also obtained, among which fourteen are new compounds. These compounds represent 11 different structural types and can be categorized into 6 groups based on their biosynthetic origin. Their structures were determined from spectroscopic analysis, quantum chemical calculation, and X-ray diffraction data. All the isolates are decorated with a methyl group at C-5 instead of a prenyl or geranyl group as in most other PPAPs. Biologically, sixteen compounds were identified as potent inhibitors of low-voltage-gated calcium channels (LVGCCs; Ca<sub>v</sub>3.1–3.3), with IC<sub>50</sub> values ranging from 1.89 to 16.55 μmol L<sup>−1</sup>. Moreover, compound exhibited strong and dose-dependent antinociception in an acetic acid-induced mouse model of visceral pain and its effect is comparable to that of Z944, a representative LVGCC inhibitor under clinical trial.</div></div>","PeriodicalId":94379,"journal":{"name":"Organic chemistry frontiers : an international journal of organic chemistry","volume":"12 7","pages":"Pages 2375-2381"},"PeriodicalIF":0.0,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143427069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Wanzhen Lin , Xin Ding , Jun-Wei Han , Li-Shuang Yu , Fa-Jie Chen
Peptide stapling has emerged as a valuable approach for modulating peptide structures and enhancing their functional properties, with broad applications for drug discovery and biomolecular engineering. Among the diverse stapling strategies, polyfluorinated reagent-mediated approaches stand out due to their unique ability to provide desirable physicochemical properties such as improved stability, lipophilicity, and binding affinity. This review highlights recent advancements in polyfluorinated reagents for native peptide stapling, focusing on three major classes: arylation, vinylation, and amidation reagents. These reagents enable precise peptide modifications by leveraging the reactivity and selectivity modulated by fluorine substituents, facilitating the engineering of native peptides and biologics.
{"title":"Polyfluorinated reagents for peptide stapling","authors":"Wanzhen Lin , Xin Ding , Jun-Wei Han , Li-Shuang Yu , Fa-Jie Chen","doi":"10.1039/d5qo00112a","DOIUrl":"10.1039/d5qo00112a","url":null,"abstract":"<div><div>Peptide stapling has emerged as a valuable approach for modulating peptide structures and enhancing their functional properties, with broad applications for drug discovery and biomolecular engineering. Among the diverse stapling strategies, polyfluorinated reagent-mediated approaches stand out due to their unique ability to provide desirable physicochemical properties such as improved stability, lipophilicity, and binding affinity. This review highlights recent advancements in polyfluorinated reagents for native peptide stapling, focusing on three major classes: arylation, vinylation, and amidation reagents. These reagents enable precise peptide modifications by leveraging the reactivity and selectivity modulated by fluorine substituents, facilitating the engineering of native peptides and biologics.</div></div>","PeriodicalId":94379,"journal":{"name":"Organic chemistry frontiers : an international journal of organic chemistry","volume":"12 8","pages":"Pages 2777-2789"},"PeriodicalIF":0.0,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143385509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ya-Zhen Zeng , Wang Zhang , Man-Yi Han , Peng Wang , Hanmin Huang
α-Carbonyl carbocations, serving as the umpolung forms of synthetically fundamental α-carbonyl carbanions, are highly reactive species. The controlled generation and subsequent strategic employment of these reactive intermediates remain challenging. Herein, we report a photoredox-catalyzed approach for generating α-carbonyl carbocations from the corresponding α-carbonyl radicals through a single electron transfer (SET) oxidation process. These α-carbonyl radicals are readily accessible through radical addition to various α,β-unsaturated carbonyl compounds, including α,β-unsaturated esters, acid, amides and ketones. Furthermore, the Ritter reaction can be initiated by addition of nitriles to α-carbonyl carbocations, enabling the general synthesis of α-tertiary amino acid derivatives. This method features mild conditions, does not require strong acids and terminal oxidants, utilizes visible light, operates without pre-functionalization, offers a broad substrate scope and good group tolerance, etc. Moreover, further extension to the late-stage modification of natural products through this photoredox-catalyzed generation and utilization of α-carbonyl carbocations is also demonstrated.
{"title":"Photoredox-catalyzed generation of α-carbonyl carbocations: general access to α-tertiary amino acid derivatives†","authors":"Ya-Zhen Zeng , Wang Zhang , Man-Yi Han , Peng Wang , Hanmin Huang","doi":"10.1039/d4qo02306d","DOIUrl":"10.1039/d4qo02306d","url":null,"abstract":"<div><div>α-Carbonyl carbocations, serving as the umpolung forms of synthetically fundamental α-carbonyl carbanions, are highly reactive species. The controlled generation and subsequent strategic employment of these reactive intermediates remain challenging. Herein, we report a photoredox-catalyzed approach for generating α-carbonyl carbocations from the corresponding α-carbonyl radicals through a single electron transfer (SET) oxidation process. These α-carbonyl radicals are readily accessible through radical addition to various α,β-unsaturated carbonyl compounds, including α,β-unsaturated esters, acid, amides and ketones. Furthermore, the Ritter reaction can be initiated by addition of nitriles to α-carbonyl carbocations, enabling the general synthesis of α-tertiary amino acid derivatives. This method features mild conditions, does not require strong acids and terminal oxidants, utilizes visible light, operates without pre-functionalization, offers a broad substrate scope and good group tolerance, <em>etc</em>. Moreover, further extension to the late-stage modification of natural products through this photoredox-catalyzed generation and utilization of α-carbonyl carbocations is also demonstrated.</div></div>","PeriodicalId":94379,"journal":{"name":"Organic chemistry frontiers : an international journal of organic chemistry","volume":"12 8","pages":"Pages 2617-2623"},"PeriodicalIF":0.0,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143435255","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Julio C. Flores-Reyes , Yoarhy A. Amador-Sánchez , Alejandro Valderrama-Celestino , Bertha D. Barrios-Campos , Ricardo A. Peralta , Michael T. Huxley , Ilich A. Ibarra , Alejandro Islas-Jácome , Diego Solis-Ibarra , Eduardo González-Zamora
The dual-state emission (DSE) phenomenon has become crucial for developing dual-state emission luminogens (DSEgens) that exhibit efficient luminescence in both solution and solid states, addressing the limitations of conventional, phase-restricted fluorophores. Compounds exhibiting excited-state intramolecular proton transfer (ESIPT) mechanisms are especially valuable for enhancing emission stability across these states, offering significant potential in optoelectronics, bioimaging, and sensing applications. In this study, we report the synthesis of six new pyrazolyl-pyrrolo[3,4-b]pyridin-5-ones through an Ugi-Zhu-3CR coupled to an aza-Diels–Alder/N-acylation/decarboxylation/dehydration cascade sequence. An X-ray ORTEP confirms unequivocally the structure of one of the synthesized compounds. These ones demonstrate intriguing photophysical properties such as large Stokes shifts (>11 900 cm−1) in solution and robust solid-state emission via ESIPT mechanism. Complementary DFT and TD-DFT calculations confirm weak but allowed transitions involving both pyrazole and pyrrolo[3,4-b]pyridin-5-one moieties, in agreement with experimental observations. This work represents the first application of an isocyanide-based multicomponent reaction for DSEgen synthesis, paving the way for innovative advances in the design of organic luminescent materials.
{"title":"Dual-state emission of pyrazolyl-pyrrolo[3,4-b]pyridin-5-ones via excited-state intramolecular proton transfer (ESIPT): multicomponent synthesis and optical characterization†","authors":"Julio C. Flores-Reyes , Yoarhy A. Amador-Sánchez , Alejandro Valderrama-Celestino , Bertha D. Barrios-Campos , Ricardo A. Peralta , Michael T. Huxley , Ilich A. Ibarra , Alejandro Islas-Jácome , Diego Solis-Ibarra , Eduardo González-Zamora","doi":"10.1039/d4qo02256d","DOIUrl":"10.1039/d4qo02256d","url":null,"abstract":"<div><div>The dual-state emission (DSE) phenomenon has become crucial for developing dual-state emission luminogens (DSEgens) that exhibit efficient luminescence in both solution and solid states, addressing the limitations of conventional, phase-restricted fluorophores. Compounds exhibiting excited-state intramolecular proton transfer (ESIPT) mechanisms are especially valuable for enhancing emission stability across these states, offering significant potential in optoelectronics, bioimaging, and sensing applications. In this study, we report the synthesis of six new pyrazolyl-pyrrolo[3,4-<em>b</em>]pyridin-5-ones through an Ugi-Zhu-3CR coupled to an aza-Diels–Alder/<em>N</em>-acylation/decarboxylation/dehydration cascade sequence. An X-ray ORTEP confirms unequivocally the structure of one of the synthesized compounds. These ones demonstrate intriguing photophysical properties such as large Stokes shifts (>11 900 cm<sup>−1</sup>) in solution and robust solid-state emission <em>via</em> ESIPT mechanism. Complementary DFT and TD-DFT calculations confirm weak but allowed transitions involving both pyrazole and pyrrolo[3,4-<em>b</em>]pyridin-5-one moieties, in agreement with experimental observations. This work represents the first application of an isocyanide-based multicomponent reaction for DSEgen synthesis, paving the way for innovative advances in the design of organic luminescent materials.</div></div>","PeriodicalId":94379,"journal":{"name":"Organic chemistry frontiers : an international journal of organic chemistry","volume":"12 8","pages":"Pages 2607-2616"},"PeriodicalIF":0.0,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143435257","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Herein we disclose a catalytic asymmetric desymmetrization of cyclopentene-1,3-diones via a formal diaza–ene reaction/tautomerization with donor–acceptor hydrazones. The H8-TRIP catalyst was found to be effective for this reaction. Chiral cyclopentane 1,3-diones with a hydrazone motif were obtained in good to high yields with excellent diastereo- and good to high enantioselectivities. The scope of the reaction was broad and a few applications including a pyrazole formation reaction have been demonstrated.
{"title":"Organocatalytic asymmetric desymmetrization of cyclopentene-1,3-diones via a formal diaza–ene reaction with donor–acceptor hydrazones†","authors":"Subhankar Biswas , Subhas Chandra Pan","doi":"10.1039/d5qo00081e","DOIUrl":"10.1039/d5qo00081e","url":null,"abstract":"<div><div>Herein we disclose a catalytic asymmetric desymmetrization of cyclopentene-1,3-diones <em>via</em> a formal diaza–ene reaction/tautomerization with donor–acceptor hydrazones. The H8-TRIP catalyst was found to be effective for this reaction. Chiral cyclopentane 1,3-diones with a hydrazone motif were obtained in good to high yields with excellent diastereo- and good to high enantioselectivities. The scope of the reaction was broad and a few applications including a pyrazole formation reaction have been demonstrated.</div></div>","PeriodicalId":94379,"journal":{"name":"Organic chemistry frontiers : an international journal of organic chemistry","volume":"12 8","pages":"Pages 2651-2657"},"PeriodicalIF":0.0,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143443950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Herein, a new one-pot transition-metal-free catalytic method for the synthesis of C3,5-disubstituted oxindoles has been developed. The protocol features good functional group tolerance, mild reaction conditions and atom economy. In addition, this protocol provides a platform for the synthesis of novel and complex oxindole derivatives with potential for biological activities.
{"title":"Transition-metal-free synthesis of C3,5-difunctionalized oxindole derivatives†","authors":"Yifeng Liu , Pengyan Zhang , Liangjie Feng , Zhuan Zhang , Taoyuan Liang","doi":"10.1039/d4qo02428a","DOIUrl":"10.1039/d4qo02428a","url":null,"abstract":"<div><div>Herein, a new one-pot transition-metal-free catalytic method for the synthesis of C3,5-disubstituted oxindoles has been developed. The protocol features good functional group tolerance, mild reaction conditions and atom economy. In addition, this protocol provides a platform for the synthesis of novel and complex oxindole derivatives with potential for biological activities.</div></div>","PeriodicalId":94379,"journal":{"name":"Organic chemistry frontiers : an international journal of organic chemistry","volume":"12 8","pages":"Pages 2704-2708"},"PeriodicalIF":0.0,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143470687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shan Wang , Ting-Ting Yuan , Jun-Ting Liang , Xiao-Xia Liang , Xuan Deng , Zichen Xu , Ya-Jian Hu , Yu-Tao He
A visible light-mediated synthesis protocol for the three-component pyridyl silylation of olefins to access β-pyridyl silicons has been developed. The reaction cascade is initiated by an in situ generated methoxy radical enabled by EDA complexes formed between the electron-deficient N-methoxypyridinium salts and a base. The reaction using hydrosilane as the silicon source to access the silyl radical proceeds well via a hydrogen atom transfer process between a silane Si–H bond and the methoxy radical. This protocol features exogenous photocatalyst-free conditions and high atom economy, thereby providing a powerful synthon for preparing silyl- and pyridyl-containing compounds with excellent functional group compatibility. Therefore, it is expected that this method will find applications in synthetic chemistry and drug discovery.
{"title":"Visible light-mediated pyridyl silylation of olefins through hydrogen atom transfer†","authors":"Shan Wang , Ting-Ting Yuan , Jun-Ting Liang , Xiao-Xia Liang , Xuan Deng , Zichen Xu , Ya-Jian Hu , Yu-Tao He","doi":"10.1039/d5qo00085h","DOIUrl":"10.1039/d5qo00085h","url":null,"abstract":"<div><div>A visible light-mediated synthesis protocol for the three-component pyridyl silylation of olefins to access β-pyridyl silicons has been developed. The reaction cascade is initiated by an <em>in situ</em> generated methoxy radical enabled by EDA complexes formed between the electron-deficient <em>N</em>-methoxypyridinium salts and a base. The reaction using hydrosilane as the silicon source to access the silyl radical proceeds well <em>via</em> a hydrogen atom transfer process between a silane Si–H bond and the methoxy radical. This protocol features exogenous photocatalyst-free conditions and high atom economy, thereby providing a powerful synthon for preparing silyl- and pyridyl-containing compounds with excellent functional group compatibility. Therefore, it is expected that this method will find applications in synthetic chemistry and drug discovery.</div></div>","PeriodicalId":94379,"journal":{"name":"Organic chemistry frontiers : an international journal of organic chemistry","volume":"12 8","pages":"Pages 2720-2726"},"PeriodicalIF":0.0,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143470686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xinru Liang , Junjie Shi , Qiuju Zhong , Lai Li , Yutao Liu , Tong Sun , Junxi Liang , Xianying Shi , Gaoqiang Li , Mingyu Yang
The modification of peptides can considerably change their functions, thus facilitating the development of peptides for use as drugs, therapeutics, and diagnostics, and in chemical biology. Transition-metal catalyzed cross-coupling is a promising method to accomplish peptide modification, but the chemoselective introduction of a new C(sp2)–N bond at a tryptophan residue is a challenging yet crucial task. Herein, the functionalization of peptides achieved through the copper-catalyzed Ullmann coupling of tryptophan with aryl halides containing multiple functional groups is reported, which enabled the arylation of the indole side chain of tryptophan. This method features remarkable tolerance of diverse functional groups, scalability, and distinct chemoselectivity toward tryptophan residues. The fusion of different functional groups demonstrated the potential utility of this approach, offering new avenues to modify the side chains of proteinogenic amino acids.
{"title":"Selective functionalization of Trp residues via copper-catalyzed Ullmann coupling†","authors":"Xinru Liang , Junjie Shi , Qiuju Zhong , Lai Li , Yutao Liu , Tong Sun , Junxi Liang , Xianying Shi , Gaoqiang Li , Mingyu Yang","doi":"10.1039/d4qo02073a","DOIUrl":"10.1039/d4qo02073a","url":null,"abstract":"<div><div>The modification of peptides can considerably change their functions, thus facilitating the development of peptides for use as drugs, therapeutics, and diagnostics, and in chemical biology. Transition-metal catalyzed cross-coupling is a promising method to accomplish peptide modification, but the chemoselective introduction of a new C(sp<sup>2</sup>)–N bond at a tryptophan residue is a challenging yet crucial task. Herein, the functionalization of peptides achieved through the copper-catalyzed Ullmann coupling of tryptophan with aryl halides containing multiple functional groups is reported, which enabled the arylation of the indole side chain of tryptophan. This method features remarkable tolerance of diverse functional groups, scalability, and distinct chemoselectivity toward tryptophan residues. The fusion of different functional groups demonstrated the potential utility of this approach, offering new avenues to modify the side chains of proteinogenic amino acids.</div></div>","PeriodicalId":94379,"journal":{"name":"Organic chemistry frontiers : an international journal of organic chemistry","volume":"12 7","pages":"Pages 2332-2339"},"PeriodicalIF":0.0,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143027042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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