3-Substituted-3-hydroxy oxindoles were synthesized via diastereoselective nucleophilic additions to an axially chiral racemic N-aryl isatin bearing an ortho-dimethylamino group on a p-(benzyloxy)aryl moiety. A switch in diastereoselectivity was observed (up to anti:syn = 29:71 to 74:26) depending on the organometallic reagent (RLi or RMgX). The p-(benzyloxy)aryl moiety was readily removed via a mild two-step sequence to afford NH oxindole.
{"title":"Diastereoselective synthesis of 3-substituted-3-hydroxy oxindoles from atropisomeric N-aryl isatin bearing an ortho-dimethylamino group","authors":"Seiryu Tabata , Yuuya Kawasaki , Kazunobu Igawa , Katsuhiko Tomooka , Atsuo Nakazaki","doi":"10.1016/j.tetlet.2025.155817","DOIUrl":"10.1016/j.tetlet.2025.155817","url":null,"abstract":"<div><div>3-Substituted-3-hydroxy oxindoles were synthesized via diastereoselective nucleophilic additions to an axially chiral racemic <em>N</em>-aryl isatin bearing an <em>ortho</em>-dimethylamino group on a <em>p</em>-(benzyloxy)aryl moiety. A switch in diastereoselectivity was observed (up to <em>anti</em>:<em>syn</em> = 29:71 to 74:26) depending on the organometallic reagent (RLi or RMgX). The <em>p</em>-(benzyloxy)aryl moiety was readily removed via a mild two-step sequence to afford N<img>H oxindole.</div></div>","PeriodicalId":438,"journal":{"name":"Tetrahedron Letters","volume":"171 ","pages":"Article 155817"},"PeriodicalIF":1.5,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145019783","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-09-02DOI: 10.1016/j.tetlet.2025.155802
Ramsha Iftikhar , Mohan Bhadbhade , Ruoming Tian , Giancarlo Pascali , Roger Read , Luke Hunter
A concise total synthesis of the C2-symmetric marine alkaloid, phenazine-1,6-diyldimethanol, is reported. X-ray crystal structures for three phenazine derivatives are presented, and a simple and general NMR-based method for distinguishing 1,6- from 1,9-disubstituted phenazines is described.
{"title":"Synthesis of phenazine-1,6-diyldimethanol, a natural product from Brevibacteria","authors":"Ramsha Iftikhar , Mohan Bhadbhade , Ruoming Tian , Giancarlo Pascali , Roger Read , Luke Hunter","doi":"10.1016/j.tetlet.2025.155802","DOIUrl":"10.1016/j.tetlet.2025.155802","url":null,"abstract":"<div><div>A concise total synthesis of the C2-symmetric marine alkaloid, phenazine-1,6-diyldimethanol, is reported. X-ray crystal structures for three phenazine derivatives are presented, and a simple and general NMR-based method for distinguishing 1,6- from 1,9-disubstituted phenazines is described.</div></div>","PeriodicalId":438,"journal":{"name":"Tetrahedron Letters","volume":"171 ","pages":"Article 155802"},"PeriodicalIF":1.5,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144933078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Phytochemical investigation of a methanol extract of the twigs and leaves of Buxus bodinieri led to the isolation of four new triterpenoid alkaloids (1–4) and five known analogues (5–9). Their structures were determined by extensive analyses of their spectroscopic data and corroborated by the single-crystal X-ray diffraction. In LPS-induced RAW264.7 cells model, compounds 1 and 2 displayed the most potent anti-inflammatory effects, with IC50 values of 7.5 and 6.1 μM, respectively. Compounds 2 and 6 also exhibited significant cytotoxic activity against HT-29 cell line (IC50 of 6.4 and 10.2 μM), representing 2.9-fold and 1.8-fold greater potency than the positive control cisplatin (IC50 = 18.6 μM), respectively.
{"title":"Triterpenoid alkaloids from Buxus bodinieri and their bioactivities","authors":"Hong-Jing Zha , Chun-Xia Chen , Xing Sun , Shi-Ying Yuan","doi":"10.1016/j.tetlet.2025.155815","DOIUrl":"10.1016/j.tetlet.2025.155815","url":null,"abstract":"<div><div>Phytochemical investigation of a methanol extract of the twigs and leaves of <em>Buxus bodinieri</em> led to the isolation of four new triterpenoid alkaloids (<strong>1</strong>–<strong>4</strong>) and five known analogues (<strong>5</strong>–<strong>9</strong>). Their structures were determined by extensive analyses of their spectroscopic data and corroborated by the single-crystal X-ray diffraction. In LPS-induced RAW264.7 cells model, compounds <strong>1</strong> and <strong>2</strong> displayed the most potent anti-inflammatory effects, with IC<sub>50</sub> values of 7.5 and 6.1 μM, respectively. Compounds <strong>2</strong> and <strong>6</strong> also exhibited significant cytotoxic activity against HT-29 cell line (IC50 of 6.4 and 10.2 μM), representing 2.9-fold and 1.8-fold greater potency than the positive control cisplatin (IC<sub>50</sub> = 18.6 μM), respectively.</div></div>","PeriodicalId":438,"journal":{"name":"Tetrahedron Letters","volume":"171 ","pages":"Article 155815"},"PeriodicalIF":1.5,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145010359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A practical synthetic method for the ethynyl trifluoromethyl sulfides through AgSCF3-mediated direct trifluoromethylthiolation has been developed. The reaction of the alkynyl iodides by CuI with 4,4′-di-tert-butyl-2,2′-bipyridine is performed under mild reaction conditions. This transformation efficiently affords aryl or alkyl acetenyl trifluoromethyl sulfides with good reaction yields, broad substrate scope, excellent compatibility and operational simplicity.
{"title":"AgSCF3-mediated direct Trifluoromethylthiolation of alkynyl iodides for aryl and alkyl ethynyl trifluoromethyl Sulfides","authors":"Jianquan Hong, Qiang Wang, Chunxiang Li, Shengying Gu, Jie Wang, Xifei Chen, Chongbin Wei, Xinxin Gong, Wenqi Li, Changge Zheng","doi":"10.1016/j.tetlet.2025.155816","DOIUrl":"10.1016/j.tetlet.2025.155816","url":null,"abstract":"<div><div>A practical synthetic method for the ethynyl trifluoromethyl sulfides through AgSCF<sub>3</sub>-mediated direct trifluoromethylthiolation has been developed. The reaction of the alkynyl iodides by CuI with 4,4′-di-<em>tert</em>-butyl-2,2′-bipyridine is performed under mild reaction conditions. This transformation efficiently affords aryl or alkyl acetenyl trifluoromethyl sulfides with good reaction yields, broad substrate scope, excellent compatibility and operational simplicity.</div></div>","PeriodicalId":438,"journal":{"name":"Tetrahedron Letters","volume":"171 ","pages":"Article 155816"},"PeriodicalIF":1.5,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144988834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-30DOI: 10.1016/j.tetlet.2025.155801
Luis A. Segura-Quezada , Melissa Tapia-Juárez , Miriam P. Barrera-Nava , Luis Chacón-García , César R. Solorio-Alvarado
Quinones are essential compounds in organic synthesis due to their versatility and diverse range of applications in areas such as drug design, material science, and catalysis. Historically, quinone compounds preparation has attracted significant interest, with electrochemical methods being a notable approach among the available techniques. With a long-standing history, organic electrosynthesis represents a renewed strategy. It offers sustainability, as it does not demand the use of potential oxidants or reductants, thereby reducing the potential for negative environmental impacts and health hazards. This review offers a comprehensive overview of the historical and synthetic background of quinone electrosynthesis, highlighting its importance and relevance.
{"title":"Electrosynthesis of quinones, a brief overview","authors":"Luis A. Segura-Quezada , Melissa Tapia-Juárez , Miriam P. Barrera-Nava , Luis Chacón-García , César R. Solorio-Alvarado","doi":"10.1016/j.tetlet.2025.155801","DOIUrl":"10.1016/j.tetlet.2025.155801","url":null,"abstract":"<div><div>Quinones are essential compounds in organic synthesis due to their versatility and diverse range of applications in areas such as drug design, material science, and catalysis. Historically, quinone compounds preparation has attracted significant interest, with electrochemical methods being a notable approach among the available techniques. With a long-standing history, organic electrosynthesis represents a renewed strategy. It offers sustainability, as it does not demand the use of potential oxidants or reductants, thereby reducing the potential for negative environmental impacts and health hazards. This review offers a comprehensive overview of the historical and synthetic background of quinone electrosynthesis, highlighting its importance and relevance.</div><div>2009 Elsevier Ltd. All rights reserved.</div></div>","PeriodicalId":438,"journal":{"name":"Tetrahedron Letters","volume":"171 ","pages":"Article 155801"},"PeriodicalIF":1.5,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144918133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-29DOI: 10.1016/j.tetlet.2025.155800
Giovanni Roviello , Caterina Cioffi , Maria Moccia , Malachi W. Gillick-Healy , Brian G. Kelly , Mauro F.A. Adamo
An innovative preparation of the Active Pharmaceutical Ingredient (API) Atomoxetine has been developed. Key advantages of the synthetic procedure include: a one-pot preparation of a 1,3-bis-electrophilic phenyl-propionic synthon obtained via desulfurative chlorination of an easy to make thiophenyl sulfide; an unreported strategy for the preparation of secondary amines. The synthesis involves a total of four consecutive steps from unexpensive and readily available reagents and employes mild conditions.
{"title":"Synthesis of active pharmaceutical ingredient atomoxetine via desulfurative halogenation","authors":"Giovanni Roviello , Caterina Cioffi , Maria Moccia , Malachi W. Gillick-Healy , Brian G. Kelly , Mauro F.A. Adamo","doi":"10.1016/j.tetlet.2025.155800","DOIUrl":"10.1016/j.tetlet.2025.155800","url":null,"abstract":"<div><div>An innovative preparation of the Active Pharmaceutical Ingredient (API) Atomoxetine has been developed. Key advantages of the synthetic procedure include: a one-pot preparation of a 1,3-bis-electrophilic phenyl-propionic synthon obtained <em>via</em> desulfurative chlorination of an easy to make thiophenyl sulfide; an unreported strategy for the preparation of secondary amines. The synthesis involves a total of four consecutive steps from unexpensive and readily available reagents and employes mild conditions.</div></div>","PeriodicalId":438,"journal":{"name":"Tetrahedron Letters","volume":"171 ","pages":"Article 155800"},"PeriodicalIF":1.5,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144913807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-28DOI: 10.1016/j.tetlet.2025.155814
Marcelo Fiori Marchiori , Maria Angélica dos Santos Cunha Chellegatti , João Victor Silveira Camargo , Vânia Santos Braz , Sérgio R. Ambrósio , Jairo Kenupp Bastos , Guilherme Martins Silva , Niege Araçari Jacometti Cardoso Furtado , Vanessa Leiria Campo
The increasing number of fungal infections and resistance to available drugs represent a serious threat to public health. In this context, the aim of this work was the synthesis of a novel series of polyalthic acid-1,2,3-triazole-arylsulfonamide derivatives by Cu(I)-catalysed azide-alkyne cycloaddition reactions (“click chemistry”), along with the evaluation of their antifungal properties against three Candida species. The best activities were observed for compounds 4, 6 and 7 against Candida albicans (MIC/MFC 6.25 to 12.5 μg/ml), and for compounds 9 and 3 against Candida krusei (MIC/ MFC 12.5 to 50 μg/ml). These findings highlight the potential of polyalthic acid derivatives as viable candidates for the development of new triazole antifungal agents.
{"title":"Synthesis and antifungal activity of polyalthic acid-1,2,3-triazole-arylsulfonamide derivatives","authors":"Marcelo Fiori Marchiori , Maria Angélica dos Santos Cunha Chellegatti , João Victor Silveira Camargo , Vânia Santos Braz , Sérgio R. Ambrósio , Jairo Kenupp Bastos , Guilherme Martins Silva , Niege Araçari Jacometti Cardoso Furtado , Vanessa Leiria Campo","doi":"10.1016/j.tetlet.2025.155814","DOIUrl":"10.1016/j.tetlet.2025.155814","url":null,"abstract":"<div><div>The increasing number of fungal infections and resistance to available drugs represent a serious threat to public health. In this context, the aim of this work was the synthesis of a novel series of polyalthic acid-1,2,3-triazole-arylsulfonamide derivatives by Cu(I)-catalysed azide-alkyne cycloaddition reactions (“click chemistry”), along with the evaluation of their antifungal properties against three <em>Candida</em> species. The best activities were observed for compounds <strong>4</strong>, <strong>6</strong> and <strong>7</strong> against <em>Candida albicans</em> (MIC/MFC 6.25 to 12.5 μg/ml), and for compounds <strong>9</strong> and <strong>3</strong> against <em>Candida krusei</em> (MIC/ MFC 12.5 to 50 μg/ml). These findings highlight the potential of polyalthic acid derivatives as viable candidates for the development of new triazole antifungal agents.</div></div>","PeriodicalId":438,"journal":{"name":"Tetrahedron Letters","volume":"171 ","pages":"Article 155814"},"PeriodicalIF":1.5,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144913808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-28DOI: 10.1016/j.tetlet.2025.155813
Jiahong Chen , Hanjing Deng , Pengyu Zhang, You Zi
A strategy for amide synthesis through the deoxygenation of carboxylic acids with N-chloro compounds using a phosphine-mediated P(V) platform is reported. This method enables the efficient conversion of various carboxylic acids, including primary, secondary, and bioactive molecules, as well as amino acids, into amides under mild conditions. The scalability of the reaction highlights its practical applicability for large-scale amide production. This approach offers a new perspective on activation reagents, focusing on aniline activation rather than conventional carboxylic acid activation.
{"title":"Phosphine-mediated deoxygenative synthesis of amides from carboxylic acids and N-chloro compounds","authors":"Jiahong Chen , Hanjing Deng , Pengyu Zhang, You Zi","doi":"10.1016/j.tetlet.2025.155813","DOIUrl":"10.1016/j.tetlet.2025.155813","url":null,"abstract":"<div><div>A strategy for amide synthesis through the deoxygenation of carboxylic acids with N-chloro compounds using a phosphine-mediated P(V) platform is reported. This method enables the efficient conversion of various carboxylic acids, including primary, secondary, and bioactive molecules, as well as amino acids, into amides under mild conditions. The scalability of the reaction highlights its practical applicability for large-scale amide production. This approach offers a new perspective on activation reagents, focusing on aniline activation rather than conventional carboxylic acid activation.</div></div>","PeriodicalId":438,"journal":{"name":"Tetrahedron Letters","volume":"171 ","pages":"Article 155813"},"PeriodicalIF":1.5,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144926366","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-08-25DOI: 10.1016/j.tetlet.2025.155803
Nidhi Saini, Khushboo Gupta, Chhavi Khajuria, Vinod K. Singh
A highly enantioselective organocatalytic Mannich reaction between 2-fluoro-1,3-diketones and β,γ-alkynyl-α-imino esters has been developed, utilizing a chiral bifunctional urea catalyst. This strategy provides efficient access to a diverse range of fluorinated and non-fluorinated unnatural α-amino acid derivatives with excellent yields (up to 98 %) and enantioselectivities (up to 97 %). A wide array of substrates bearing diverse substituents is compatible with this reaction, showcasing its broad scope. The practicality of this approach was further highlighted by the successful scale-up reaction and subsequent transformations of the fluorinated amino acid derivatives.
{"title":"Enantioselective Mannich reaction of 2-fluoro-1,3-diketones to ketimines: access to fluorinated α-amino acid derivatives","authors":"Nidhi Saini, Khushboo Gupta, Chhavi Khajuria, Vinod K. Singh","doi":"10.1016/j.tetlet.2025.155803","DOIUrl":"10.1016/j.tetlet.2025.155803","url":null,"abstract":"<div><div>A highly enantioselective organocatalytic Mannich reaction between 2-fluoro-1,3-diketones and β,γ-alkynyl-α-imino esters has been developed, utilizing a chiral bifunctional urea catalyst. This strategy provides efficient access to a diverse range of fluorinated and non-fluorinated unnatural α-amino acid derivatives with excellent yields (up to 98 %) and enantioselectivities (up to 97 %). A wide array of substrates bearing diverse substituents is compatible with this reaction, showcasing its broad scope. The practicality of this approach was further highlighted by the successful scale-up reaction and subsequent transformations of the fluorinated amino acid derivatives.</div></div>","PeriodicalId":438,"journal":{"name":"Tetrahedron Letters","volume":"171 ","pages":"Article 155803"},"PeriodicalIF":1.5,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144907348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The STU ring of maitotoxin (MTX) was synthesized from a common intermediate of the QRS ring of MTX via β-borylation/oxidation of an enone, ring expansion of a six-membered ring ketone to a seven-membered one, and methylation of an O,S-acetal in 8 steps.
以maitotoxin (MTX) QRS环的共同中间体为原料，经β-硼化/氧化烯酮、六元环酮扩环为七元环酮、O， s -缩醛甲基化共8步合成了maitotoxin （MTX）的STU环。
{"title":"Synthesis of STU ring of maitotoxin","authors":"Takahiro Harada , Hiroshi Yamaguchi , Keitaro Umeno , Yoko Yasuno , Hiroshi Tsuchikawa , Masayuki Satake , Tohru Oishi","doi":"10.1016/j.tetlet.2025.155799","DOIUrl":"10.1016/j.tetlet.2025.155799","url":null,"abstract":"<div><div>The STU ring of maitotoxin (MTX) was synthesized from a common intermediate of the QRS ring of MTX via β-borylation/oxidation of an enone, ring expansion of a six-membered ring ketone to a seven-membered one, and methylation of an <em>O</em>,<em>S</em>-acetal in 8 steps.</div></div>","PeriodicalId":438,"journal":{"name":"Tetrahedron Letters","volume":"171 ","pages":"Article 155799"},"PeriodicalIF":1.5,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144907349","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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