In this study, a direct synthetic methodology for the construction of dihydronaphtho[2,1-c]chromene scaffold derivatives has been developed. Via the benzyne-participating Diels-Alder route, the naphtho[2,1-c]chromene skeleton possessing promising biological activity could be efficiently furnished under mild conditions.
{"title":"Construction of functionalized naphtho[2,1-c]chromene scaffolds by Diels-Alder reaction using benzyne as dienophiles","authors":"Chuanlin Lan, Yingyi Wang, Feng Sha, Xinyan Wu, Yian Cui, Yi Zheng","doi":"10.1016/j.tetlet.2024.155430","DOIUrl":"10.1016/j.tetlet.2024.155430","url":null,"abstract":"<div><div>In this study, a direct synthetic methodology for the construction of dihydronaphtho[2,1-<em>c</em>]chromene scaffold derivatives has been developed. Via the benzyne-participating Diels-Alder route, the naphtho[2,1-<em>c</em>]chromene skeleton possessing promising biological activity could be efficiently furnished under mild conditions.</div></div>","PeriodicalId":438,"journal":{"name":"Tetrahedron Letters","volume":"155 ","pages":"Article 155430"},"PeriodicalIF":1.5,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143159587","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 : 2025-01-27DOI: 10.1016/j.tetlet.2025.155488
Shuntaro Tsukamoto, Yuki Suzuki, Masato Oikawa
We report herein an unprecedented concept for an enantiospecific synthetic strategy for α–amino acid derivatives starting from Ugi four-component coupling reaction employing chiral amine, via a chiral morpholinone intermediate. This concept was proven by the successful synthesis of (S)–N–Ac–tert–leucine.
{"title":"Stereocontrolled synthesis of an α–monosubstituted α–amino acid derivative from a Ugi reaction product","authors":"Shuntaro Tsukamoto, Yuki Suzuki, Masato Oikawa","doi":"10.1016/j.tetlet.2025.155488","DOIUrl":"10.1016/j.tetlet.2025.155488","url":null,"abstract":"<div><div>We report herein an unprecedented concept for an enantiospecific synthetic strategy for α–amino acid derivatives starting from Ugi four-component coupling reaction employing chiral amine, via a chiral morpholinone intermediate. This concept was proven by the successful synthesis of (<em>S</em>)–<em>N</em>–Ac–<em>tert</em>–leucine.</div></div>","PeriodicalId":438,"journal":{"name":"Tetrahedron Letters","volume":"157 ","pages":"Article 155488"},"PeriodicalIF":1.5,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143150501","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 : 2025-01-27DOI: 10.1016/j.tetlet.2025.155490
Kuga Arima, Kenichi Matsuda, Toshiyuki Wakimoto
15N-Labeled amino acids are utilized across a wide range of research fields in biology and chemistry. However, 15N-labeled materials are typically not readily available, hindering broader applications despite their versatility. In this study, we developed a facile synthetic method for 15N-labeled amino acid hydrochlorides, using a cost-effective and easy-to-handle 15N-ammonium salt as the 15N source. This method employs 15N-labeled phthalimide as a key synthetic intermediate, which is subsequently coupled with hydroxy acid derivatives under Mitsunobu conditions to afford the corresponding amino acids, providing efficient access to various 15N-labeled amino acids.
{"title":"Facile Synthesis of 15N-Labeled Amino Acids Using 15N-Ammonium Salt","authors":"Kuga Arima, Kenichi Matsuda, Toshiyuki Wakimoto","doi":"10.1016/j.tetlet.2025.155490","DOIUrl":"10.1016/j.tetlet.2025.155490","url":null,"abstract":"<div><div><sup>15</sup>N-Labeled amino acids are utilized across a wide range of research fields in biology and chemistry. However, <sup>15</sup>N-labeled materials are typically not readily available, hindering broader applications despite their versatility. In this study, we developed a facile synthetic method for <sup>15</sup>N-labeled amino acid hydrochlorides, using a cost-effective and easy-to-handle <sup>15</sup>N-ammonium salt as the <sup>15</sup>N source. This method employs <sup>15</sup>N-labeled phthalimide as a key synthetic intermediate, which is subsequently coupled with hydroxy acid derivatives under Mitsunobu conditions to afford the corresponding amino acids, providing efficient access to various <sup>15</sup>N-labeled amino acids.</div></div>","PeriodicalId":438,"journal":{"name":"Tetrahedron Letters","volume":"157 ","pages":"Article 155490"},"PeriodicalIF":1.5,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143150504","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 : 2025-01-27DOI: 10.1016/j.tetlet.2025.155491
Koki Sugiura , Yuta Morishita , Yuto Shimoda , Takashi Fujimoto , Tomoyuki Fujita , Ayumi Tsutsui
Polyamines are important biological compounds. Mammals, including humans, biosynthesize polyamines in vivo or ingest them as food constituents. Spermidine is a reactive nucleophilic polyamine that reacts readily with aldehydes and carbonyls. In this study, a new tetrahydropyrimidine compound (MG-HSpd) is reported from the reaction of spermidine with methylglyoxal, a carbonyl stress substance produced by autoxidation of glucose. MG-HSpd was confirmed as a constituent of wheat germ crackers after the reaction of spermidine and methylglyoxal during the baking process.
{"title":"Identification of a new tetrahydropyrimidine compound derived from glycation mimic reaction of spermidine and methylglyoxal in wheat germ crackers","authors":"Koki Sugiura , Yuta Morishita , Yuto Shimoda , Takashi Fujimoto , Tomoyuki Fujita , Ayumi Tsutsui","doi":"10.1016/j.tetlet.2025.155491","DOIUrl":"10.1016/j.tetlet.2025.155491","url":null,"abstract":"<div><div>Polyamines are important biological compounds. Mammals, including humans, biosynthesize polyamines in vivo or ingest them as food constituents. Spermidine is a reactive nucleophilic polyamine that reacts readily with aldehydes and carbonyls. In this study, a new tetrahydropyrimidine compound (MG-HSpd) is reported from the reaction of spermidine with methylglyoxal, a carbonyl stress substance produced by autoxidation of glucose. MG-HSpd was confirmed as a constituent of wheat germ crackers after the reaction of spermidine and methylglyoxal during the baking process.</div></div>","PeriodicalId":438,"journal":{"name":"Tetrahedron Letters","volume":"157 ","pages":"Article 155491"},"PeriodicalIF":1.5,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143150502","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 : 2025-01-27DOI: 10.1016/j.tetlet.2025.155489
Nilesh B. Patil , Rhutuja Patil , Ganesh U. Chaturbhuj
This report describes an efficient method for synthesizing isoxazolines from aldoximes using NCBSI as a reagent. In this protocol, N-chloro-N-(phenylsulfonyl)benzene sulfonamide (NCBSI) oxidized aldoximes into nitrile oxide. The nitrile oxide underwent 1,3-dipolar cycloaddition to alkenes, giving isoxazolines in good to excellant yields. Furthermore, the precursor N-(phenylsulfonyl)benzene sulfonamide was recovered and transformed to NCBSI, making the protocol eco-friendly and cost-effective.
{"title":"NCBSI/TEA: A reagent system for rapid and efficient synthesis of isoxazolines from aldoxime","authors":"Nilesh B. Patil , Rhutuja Patil , Ganesh U. Chaturbhuj","doi":"10.1016/j.tetlet.2025.155489","DOIUrl":"10.1016/j.tetlet.2025.155489","url":null,"abstract":"<div><div>This report describes an efficient method for synthesizing isoxazolines from aldoximes using NCBSI as a reagent. In this protocol, <em>N</em>-chloro-<em>N</em>-(phenylsulfonyl)benzene sulfonamide (NCBSI) oxidized aldoximes into nitrile oxide. The nitrile oxide underwent 1,3-dipolar cycloaddition to alkenes, giving isoxazolines in good to excellant yields. Furthermore, the precursor <em>N</em>-(phenylsulfonyl)benzene sulfonamide was recovered and transformed to NCBSI, making the protocol eco-friendly and cost-effective.</div></div>","PeriodicalId":438,"journal":{"name":"Tetrahedron Letters","volume":"157 ","pages":"Article 155489"},"PeriodicalIF":1.5,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143150503","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 : 2025-01-27DOI: 10.1016/j.tetlet.2025.155487
Yu Bao, HaiHui Zhu, Hai Huang
Selective nonclassic propargylic substitutions have been a research focus in recent years. Herein, we developed a tandem γ-selective propargylic substitution and ring closure reaction of vinyl ethynylethylene carbonates (VEECs), efficiently synthesizing a series of 4H-pyran compounds. Additionally, the synthetic applications demonstrated that the products have significant synthetic potential in the synthesis of spirocyclic compounds.
{"title":"Copper-catalyzed γ-selective yne-allylic substitution of vinyl ethynylethylene carbonates towards a formal [3 + 3] cycloaddition","authors":"Yu Bao, HaiHui Zhu, Hai Huang","doi":"10.1016/j.tetlet.2025.155487","DOIUrl":"10.1016/j.tetlet.2025.155487","url":null,"abstract":"<div><div>Selective nonclassic propargylic substitutions have been a research focus in recent years. Herein, we developed a tandem γ-selective propargylic substitution and ring closure reaction of vinyl ethynylethylene carbonates (VEECs), efficiently synthesizing a series of 4<em>H</em>-pyran compounds. Additionally, the synthetic applications demonstrated that the products have significant synthetic potential in the synthesis of spirocyclic compounds.</div></div>","PeriodicalId":438,"journal":{"name":"Tetrahedron Letters","volume":"158 ","pages":"Article 155487"},"PeriodicalIF":1.5,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143132699","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 : 2025-01-24DOI: 10.1016/j.tetlet.2025.155480
Yabo Deng , Yisheng Cao , Yi Zhou , Zhiqiang Shen , Danna Chen , Shunqing Wang , Wenjin Yan , Jian Han , Jinqi Huang
Protein bioconjugation technology integrates the fields of synthetic chemistry and molecular biology, where N-terminal amino groups are increasingly targeted for site-specific modification strategies due to their unique properties. Herein, we report a novel approach to achieve bioconjugation of cysteine and N-terminal amino groups using multifunctional allyl sulfone-activated esters. The experiments were performed in a biocompatible environment (pH 7.4, 10 mM PBS, 37 °C) with universal sequence compatibility for unprotected random peptides of different lengths. Cyclic peptides show desirable late functionalization modifications (including biotin, alkynyl, and PEG et al.).
{"title":"Multifunctional Cys labeling-directed N-terminus-selective stapling strategy development","authors":"Yabo Deng , Yisheng Cao , Yi Zhou , Zhiqiang Shen , Danna Chen , Shunqing Wang , Wenjin Yan , Jian Han , Jinqi Huang","doi":"10.1016/j.tetlet.2025.155480","DOIUrl":"10.1016/j.tetlet.2025.155480","url":null,"abstract":"<div><div>Protein bioconjugation technology integrates the fields of synthetic chemistry and molecular biology, where <em>N</em>-terminal amino groups are increasingly targeted for site-specific modification strategies due to their unique properties. Herein, we report a novel approach to achieve bioconjugation of cysteine and <em>N</em>-terminal amino groups using multifunctional allyl sulfone-activated esters. The experiments were performed in a biocompatible environment (pH 7.4, 10 mM PBS, 37 °C) with universal sequence compatibility for unprotected random peptides of different lengths. Cyclic peptides show desirable late functionalization modifications (including biotin, alkynyl, and PEG et al.).</div></div>","PeriodicalId":438,"journal":{"name":"Tetrahedron Letters","volume":"157 ","pages":"Article 155480"},"PeriodicalIF":1.5,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143150495","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 : 2025-01-20DOI: 10.1016/j.tetlet.2025.155471
Ryanne K. Ballard, Clifford E. Berkman
N-ε-Phosphorylated lysine (pLys) residues have been understudied due to their presumed instability to withstand the conventional acidic conditions used in phosphoprotein and phosphopeptide analysis. While some efforts have been made to develop non-hydrolysable pLys surrogates, less progress has been made on developing methods to prepare authentic pLys residue and its derivatives. This study provides a synthetic route to N-ε-phosphorylated lysine models and assesses their pH-dependent stability by use of 31P NMR and HPLC. While the pLys models expectedly showed instability at lower pH (3.5), they showed unexpected stability in moderately acidic conditions (pH 5.0). In addition, the pLys models were sufficiently stable when analyzed utilizing HPLC gradients with an acid modifier (0.1 % TFA).
{"title":"Synthesis and stability of N-ε-phospholysine derivatives","authors":"Ryanne K. Ballard, Clifford E. Berkman","doi":"10.1016/j.tetlet.2025.155471","DOIUrl":"10.1016/j.tetlet.2025.155471","url":null,"abstract":"<div><div><em>N-ε</em>-Phosphorylated lysine (<em>p</em>Lys) residues have been understudied due to their presumed instability to withstand the conventional acidic conditions used in phosphoprotein and phosphopeptide analysis. While some efforts have been made to develop non-hydrolysable <em>p</em>Lys surrogates, less progress has been made on developing methods to prepare authentic <em>p</em>Lys residue and its derivatives. This study provides a synthetic route to <em>N-ε</em>-phosphorylated lysine models and assesses their pH-dependent stability by use of <sup>31</sup>P NMR and HPLC. While the <em>p</em>Lys models expectedly showed instability at lower pH (3.5), they showed unexpected stability in moderately acidic conditions (pH 5.0). In addition, the <em>p</em>Lys models were sufficiently stable when analyzed utilizing HPLC gradients with an acid modifier (0.1 % TFA).</div></div>","PeriodicalId":438,"journal":{"name":"Tetrahedron Letters","volume":"157 ","pages":"Article 155471"},"PeriodicalIF":1.5,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143150497","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 synthetic methodology for constructing ent-kaurane-like tetracyclic skeletons possessing a bicyclo[3.2.1]octane moiety has been developed by employing a desymmetrizing sequential cyclization strategy. Using a symmetric diketone as a key branching point, the sequence of desymmetric Friedel–Crafts cyclization and Pd-catalyzed intramolecular α-vinylation of ketone allowed us to construct the ent-kaurane-like tetracyclic skeleton from 1,3-cyclohexanedione in four steps. In contrast, reversing the order of the cyclization steps yielded a pseudo-symmetric tetracyclic skeleton, which is also reminiscent of the kaurane framework.
{"title":"Rapid construction of a diterpene-inspired tetracyclic skeleton bearing bicyclo[3.2.1]octane rings based on desymmetrization of 1,3-diketones","authors":"Hidetoshi Kamada, Haruki Mizoguchi, Akira Sakakura","doi":"10.1016/j.tetlet.2025.155470","DOIUrl":"10.1016/j.tetlet.2025.155470","url":null,"abstract":"<div><div>A synthetic methodology for constructing <em>ent</em>-kaurane-like tetracyclic skeletons possessing a bicyclo[3.2.1]octane moiety has been developed by employing a desymmetrizing sequential cyclization strategy. Using a symmetric diketone as a key branching point, the sequence of desymmetric Friedel–Crafts cyclization and Pd-catalyzed intramolecular α-vinylation of ketone allowed us to construct the <em>ent</em>-kaurane-like tetracyclic skeleton from 1,3-cyclohexanedione in four steps. In contrast, reversing the order of the cyclization steps yielded a pseudo-symmetric tetracyclic skeleton, which is also reminiscent of the kaurane framework.</div></div>","PeriodicalId":438,"journal":{"name":"Tetrahedron Letters","volume":"157 ","pages":"Article 155470"},"PeriodicalIF":1.5,"publicationDate":"2025-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143150494","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 : 2025-01-18DOI: 10.1016/j.tetlet.2025.155468
Hongni Qin , Yong Zhang , Song Sun
Herein, we reported a visible-light-promoted trifluoromethylation/arylation of unactivated alkenes with Togni-CF3, leading to a series of trifluoromethylated indole-fused heterocycles in moderate to good yields. Mechanically, this reaction initiated by the radical addition of CF3 radical to the alkene motif, furnishing an alkyl carbon radical, followed by its addition to the aromatic ring, and then rearomatization to afford the trifluoromethylated pyrrolo[1,2–a]indoles.
{"title":"Visible-light-promoted trifluoromethylation/arylation of unactivated alkenes with Togni-CF3 for the synthesis of trifluoromethylated pyrrolo[1,2–a]indoles","authors":"Hongni Qin , Yong Zhang , Song Sun","doi":"10.1016/j.tetlet.2025.155468","DOIUrl":"10.1016/j.tetlet.2025.155468","url":null,"abstract":"<div><div>Herein, we reported a visible-light-promoted trifluoromethylation/arylation of unactivated alkenes with Togni-CF<sub>3</sub>, leading to a series of trifluoromethylated indole-fused heterocycles in moderate to good yields. Mechanically, this reaction initiated by the radical addition of CF<sub>3</sub> radical to the alkene motif, furnishing an alkyl carbon radical, followed by its addition to the aromatic ring, and then rearomatization to afford the trifluoromethylated pyrrolo[1,2–<em>a</em>]indoles.</div></div>","PeriodicalId":438,"journal":{"name":"Tetrahedron Letters","volume":"157 ","pages":"Article 155468"},"PeriodicalIF":1.5,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143150493","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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