Synthesis of cyclohexadienone spiro-fused sultams is established through electrochemical brominative intramolecular ipso-annulation of N-aryl alkynyl sulphonamides. A range of aryl/heteroarylated-alkynyl sulphonamides are suitable under external oxidant-free electrochemical conditions. Lithium bromide is used as bromine source in this domino bromination/ipso-cyclization, leading to the corresponding bromo spiro-sultams in good yields.
{"title":"An entry to spiro-fused sultams via electrochemical brominative ipso-annulation of N-aryl alkynyl sulphonamides","authors":"Chada Raji Reddy , Maramoni Shivudu , Anjali Rathaur","doi":"10.1016/j.tetlet.2024.155330","DOIUrl":"10.1016/j.tetlet.2024.155330","url":null,"abstract":"<div><div>Synthesis of cyclohexadienone spiro-fused sultams is established through electrochemical brominative intramolecular <em>ipso</em>-annulation of <em>N-</em>aryl alkynyl sulphonamides. A range of aryl/heteroarylated-alkynyl sulphonamides are suitable under external oxidant-free electrochemical conditions. Lithium bromide is used as bromine source in this domino bromination/<em>ipso</em>-cyclization, leading to the corresponding bromo spiro-sultams in good yields.</div></div>","PeriodicalId":438,"journal":{"name":"Tetrahedron Letters","volume":"152 ","pages":"Article 155330"},"PeriodicalIF":1.5,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142531491","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 : 2024-10-21DOI: 10.1016/j.tetlet.2024.155332
Yingxiao Gao , Feng Feng , Mingxuan Wu
Lysine methylation readers are an important class of proteins that bind site-specifically methylated proteins for downstream regulation. Chemical probes that crosslink lysine methylation readers are highly desired to investigate the proteins from cellular samples. We recently reported NleS+me2 (norleucine-ε-dimethylsulfonium) as dimethyllysine mimic selectively crosslinks corresponding methyllysine readers. Although the sulfonium tools exhibited great promise, the synthetic availability may limit broad applications. In order to incorporate the unnatural amino acid, l-Fmoc-NleSme-OH (Fmoc: fluorenyl methoxycarbonyl) was synthesized as an important building block for solid-phase peptide synthesis (SPPS) in the previous synthetic route. It took six steps with resolution of racemic mixture and radical mediated thiol-ene reaction. As a result, the synthesis was not scalable with only 4.4 % overall yield. Here we report a much-improved synthesis method so that diverse NleS+me2 peptides could be readily prepared. In addition, the new method enables preparation of selenonium peptides for methyllysine reader crosslinking. We thus believe this synthetic method will be widely used to prepare sulfonium and selenonium probes for site-selective crosslinking.
{"title":"Scalable synthesis of sulfonium and selenonium peptides for selective methyllysine reader crosslinking","authors":"Yingxiao Gao , Feng Feng , Mingxuan Wu","doi":"10.1016/j.tetlet.2024.155332","DOIUrl":"10.1016/j.tetlet.2024.155332","url":null,"abstract":"<div><div>Lysine methylation readers are an important class of proteins that bind site-specifically methylated proteins for downstream regulation. Chemical probes that crosslink lysine methylation readers are highly desired to investigate the proteins from cellular samples. We recently reported NleS<sup>+</sup>me2 (norleucine-ε-dimethylsulfonium) as dimethyllysine mimic selectively crosslinks corresponding methyllysine readers. Although the sulfonium tools exhibited great promise, the synthetic availability may limit broad applications. In order to incorporate the unnatural amino acid, <em><span>l</span></em>-Fmoc-NleSme-OH (Fmoc: fluorenyl methoxycarbonyl) was synthesized as an important building block for solid-phase peptide synthesis (SPPS) in the previous synthetic route. It took six steps with resolution of racemic mixture and radical mediated thiol-ene reaction. As a result, the synthesis was not scalable with only 4.4 % overall yield. Here we report a much-improved synthesis method so that diverse NleS<sup>+</sup>me2 peptides could be readily prepared. In addition, the new method enables preparation of selenonium peptides for methyllysine reader crosslinking. We thus believe this synthetic method will be widely used to prepare sulfonium and selenonium probes for site-selective crosslinking.</div></div>","PeriodicalId":438,"journal":{"name":"Tetrahedron Letters","volume":"151 ","pages":"Article 155332"},"PeriodicalIF":1.5,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142532503","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 highly electrophilic copper enalcarbenoid has been disclosed here for the first time for its carbenoid reactivity. The synthetic utility of the transient Cu-enalcarbenoids has been demonstrated in the Cu-catalyzed direct synthesis of 1,7-disubstituted indoles from diazoenals and N-substituted pyrroles. In this reaction, Cu-enalcarbenoid served as a 4[C] biselectrophilic synthon whereas pyrrole served as a 2[C] bisnucleophilie leading to [4+2] benzannulation.
{"title":"Copper-enalcarbenoids: Rapid access to 1,7-disubstituted indoles via [4+2] benzannulation between diazoenals and N-substituted pyrroles","authors":"Bapurao Sudam Lad, Pratap Kumar Mandal, Rahul Chakrawarti, Sreenivas Katukojvala","doi":"10.1016/j.tetlet.2024.155331","DOIUrl":"10.1016/j.tetlet.2024.155331","url":null,"abstract":"<div><div>A highly electrophilic copper enalcarbenoid has been disclosed here for the first time for its carbenoid reactivity. The synthetic utility of the transient Cu-enalcarbenoids has been demonstrated in the Cu-catalyzed direct synthesis of 1,7-disubstituted indoles from diazoenals and <em>N</em>-substituted pyrroles. In this reaction, Cu-enalcarbenoid served as a 4[C] biselectrophilic synthon whereas pyrrole served as a 2[C] bisnucleophilie leading to [4+2] benzannulation.</div></div>","PeriodicalId":438,"journal":{"name":"Tetrahedron Letters","volume":"151 ","pages":"Article 155331"},"PeriodicalIF":1.5,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142532505","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 : 2024-10-18DOI: 10.1016/j.tetlet.2024.155329
Taiwo E. Esan , Charles L. Lail III , Drashti G. Daraji , Damian J. Krysan , Timothy J. Hagen
Enzymes belonging to the Acyl-CoA/NRPS/Luciferase (ANL) superfamily of enzymes, are significant targets in drug development. One member of this superfamily is Acetyl-CoA Synthetase (ACS). This enzyme is an emerging target for the treatment of various infectious diseases and cancer. Alkyl AMP esters have emerged as potent inhibitors of ACS. Previous methods for synthesizing these esters often involved water-based reactions or necessitate purification through reverse phase prep-HPLC or ion-exchange chromatography. To address these challenges, we developed a new approach utilizing 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC·HCl) to couple 5′-adenylic acid to the corresponding alcohol, utilizing triethylamine as the base. This method yielded primary, secondary, unsaturated, and cyclic alcohols in excellent yields. Importantly, we optimized the reaction conditions to achieve excellent yield and purity without the need for reverse phase prep-HPLC or ion exchange chromatography. Instead, purification was achieved through silica gel chromatography using Biotage ® Sfar spherical silica gel.
{"title":"An improved synthesis of alkyl AMP esters","authors":"Taiwo E. Esan , Charles L. Lail III , Drashti G. Daraji , Damian J. Krysan , Timothy J. Hagen","doi":"10.1016/j.tetlet.2024.155329","DOIUrl":"10.1016/j.tetlet.2024.155329","url":null,"abstract":"<div><div>Enzymes belonging to the Acyl-CoA/NRPS/Luciferase (ANL) superfamily of enzymes, are significant targets in drug development. One member of this superfamily is Acetyl-CoA Synthetase (ACS). This enzyme is an emerging target for the treatment of various infectious diseases and cancer. Alkyl AMP esters have emerged as potent inhibitors of ACS. Previous methods for synthesizing these esters often involved water-based reactions or necessitate purification through reverse phase prep-HPLC or ion-exchange chromatography. To address these challenges, we developed a new approach utilizing 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC·HCl) to couple 5′-adenylic acid to the corresponding alcohol, utilizing triethylamine as the base. This method yielded primary, secondary, unsaturated, and cyclic alcohols in excellent yields. Importantly, we optimized the reaction conditions to achieve excellent yield and purity without the need for reverse phase prep-HPLC or ion exchange chromatography. Instead, purification was achieved through silica gel chromatography using Biotage ® Sfar spherical silica gel.</div></div>","PeriodicalId":438,"journal":{"name":"Tetrahedron Letters","volume":"151 ","pages":"Article 155329"},"PeriodicalIF":1.5,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142532502","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 : 2024-10-18DOI: 10.1016/j.tetlet.2024.155335
Fanwen Kong , Rongyi Zhang , Xiu Wang , Chuanfa Ni , Jinbo Hu
A simple and highly efficient method for the double O-difluoromethylations of diphenols in 10 min is described, using TMSCF2Br as a difluorocarbene reagent. The reactivity order of different diphenols is o-diphenol > m-diphenol > p-diphenol in the two-phase difluoromethylation reaction, which can be explained by the different lipophilicities of these different diphenols.
{"title":"Facile double O-difluoromethylations of diphenols with TMSCF2Br","authors":"Fanwen Kong , Rongyi Zhang , Xiu Wang , Chuanfa Ni , Jinbo Hu","doi":"10.1016/j.tetlet.2024.155335","DOIUrl":"10.1016/j.tetlet.2024.155335","url":null,"abstract":"<div><div>A simple and highly efficient method for the double <em>O</em>-difluoromethylations of diphenols in 10 min is described, using TMSCF<sub>2</sub>Br as a difluorocarbene reagent. The reactivity order of different diphenols is <em>o</em>-diphenol > <em>m</em>-diphenol > <em>p</em>-diphenol in the two-phase difluoromethylation reaction, which can be explained by the different lipophilicities of these different diphenols.</div></div>","PeriodicalId":438,"journal":{"name":"Tetrahedron Letters","volume":"152 ","pages":"Article 155335"},"PeriodicalIF":1.5,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142662319","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 : 2024-10-18DOI: 10.1016/j.tetlet.2024.155333
Manijeh Nematpour
In this research, a rapid and direct approach for the synthesis of benzo [1,3,4] oxadiazine derivatives via a copper-catalyzed intermolecular N-arylation of 2-iodophenol and hydrozonoyl chloride is described. The reaction occurs rapidly at room temperature, making it convenient and time-saving. No complex ligands or special equipment are required. The use of simple and readily available raw materials, without column chromatography, mild catalytic copper reaction conditions, and good yield (71–93 %), are notable features of this protocol. The [1,3,4] oxadiazine moiety is often found in drugs and other bioactive molecules.
{"title":"A new route for the synthesis of substituted benzo [1,3,4] oxadiazine derivatives via copper-catalyzed N-arylation-cyclization of hydrazonoyl chlorides and 2-iodophenol","authors":"Manijeh Nematpour","doi":"10.1016/j.tetlet.2024.155333","DOIUrl":"10.1016/j.tetlet.2024.155333","url":null,"abstract":"<div><div>In this research, a rapid and direct approach for the synthesis of benzo [1,3,4] oxadiazine derivatives via a copper-catalyzed intermolecular <em>N</em>-arylation of 2-iodophenol and hydrozonoyl chloride is described. The reaction occurs rapidly at room temperature, making it convenient and time-saving. No complex ligands or special equipment are required. The use of simple and readily available raw materials, without column chromatography, mild catalytic copper reaction conditions, and good yield (71–93 %), are notable features of this protocol. The [1,3,4] oxadiazine moiety is often found in drugs and other bioactive molecules.</div></div>","PeriodicalId":438,"journal":{"name":"Tetrahedron Letters","volume":"151 ","pages":"Article 155333"},"PeriodicalIF":1.5,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142532504","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 : 2024-10-18DOI: 10.1016/j.tetlet.2024.155334
Chris Boeke , Aerin Mellott , Gahan Lahiri, Hin Yu Kenneth Huang, Jeffrey S. Cannon
A mild, chemoselective reduction of aromatic ketones was discovered and investigated. The combination of photoredox and Lewis acid catalysis with an organic hydrogen source reduced aromatic ketones in good to high yield. Optimization found 2-phenylbenzothiazoline to be a sufficiently strong source of hydrogen in combination with an iridium photosensitizer and lanthanum triflate. Effective photomediated reduction of some substrates was also observed in the absence of photocatalyst and Lewis acid or with photocatalyst only. While yields were typically higher under catalytic conditions, some acid-sensitive substrates were more effectively reduced in the absence of Lewis acid. The reaction was generally high yielding, and chemoselective, while tolerant of complex and functionally rich molecules.
{"title":"A mild and chemoselective photoredox-catalyzed reduction of aromatic ketones","authors":"Chris Boeke , Aerin Mellott , Gahan Lahiri, Hin Yu Kenneth Huang, Jeffrey S. Cannon","doi":"10.1016/j.tetlet.2024.155334","DOIUrl":"10.1016/j.tetlet.2024.155334","url":null,"abstract":"<div><div>A mild, chemoselective reduction of aromatic ketones was discovered and investigated. The combination of photoredox and Lewis acid catalysis with an organic hydrogen source reduced aromatic ketones in good to high yield. Optimization found 2-phenylbenzothiazoline to be a sufficiently strong source of hydrogen in combination with an iridium photosensitizer and lanthanum triflate. Effective photomediated reduction of some substrates was also observed in the absence of photocatalyst and Lewis acid or with photocatalyst only. While yields were typically higher under catalytic conditions, some acid-sensitive substrates were more effectively reduced in the absence of Lewis acid. The reaction was generally high yielding, and chemoselective, while tolerant of complex and functionally rich molecules.</div></div>","PeriodicalId":438,"journal":{"name":"Tetrahedron Letters","volume":"152 ","pages":"Article 155334"},"PeriodicalIF":1.5,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142531493","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}
A3 coupling of tosylribose, primary amine and alkyne has been accomplished for the synthesis of C-alkynyl iminosugars using a catalytic amount of AgOTf under extremely mild conditions. This method is compatible with acid sensitive acetonide and cyclohexylidene and also TBS and PMB ethers The reaction proceeds through a cyclic iminium ion, which is formed from tosylribose and a primary amine followed by the attack of alkyne resulting in the formation of C-alkynyl iminosugar, which is a key intermediate of many biologically important natural products.
{"title":"AgOTf-catalyzed three-component coupling for the synthesis of C-alkynyl iminosugars","authors":"Goparaju Rakesh , V. Veerabhadra Reddy , Allam Vinaykumar , B.V. Subba Reddy","doi":"10.1016/j.tetlet.2024.155326","DOIUrl":"10.1016/j.tetlet.2024.155326","url":null,"abstract":"<div><div>A<sup>3</sup> coupling of tosylribose, primary amine and alkyne has been accomplished for the synthesis of <em>C</em>-alkynyl iminosugars using a catalytic amount of AgOTf under extremely mild conditions. This method is compatible with acid sensitive acetonide and cyclohexylidene and also TBS and PMB ethers The reaction proceeds through a cyclic iminium ion, which is formed from tosylribose and a primary amine followed by the attack of alkyne resulting in the formation of <em>C</em>-alkynyl iminosugar, which is a key intermediate of many biologically important natural products.</div></div>","PeriodicalId":438,"journal":{"name":"Tetrahedron Letters","volume":"152 ","pages":"Article 155326"},"PeriodicalIF":1.5,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142531490","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 : 2024-10-15DOI: 10.1016/j.tetlet.2024.155327
Chunyan Li , Tonghui Zhang , Menghua Dong , Lewan Li , Huan Li , Jie Zeng , Jian Lv , Haifeng Wang , Shuangxi Gu
The alkylation of tetrazole and acetone under the catalysis of TfOH has been shown to be an efficient process with high levels of regioselective control. This protocol features simple and readily accessible starting materials, unique reaction mechanism, excellent compatibility with diverse functional groups.
{"title":"Brønsted acid-catalyzed selective alkylation of tetrazoles with acetone","authors":"Chunyan Li , Tonghui Zhang , Menghua Dong , Lewan Li , Huan Li , Jie Zeng , Jian Lv , Haifeng Wang , Shuangxi Gu","doi":"10.1016/j.tetlet.2024.155327","DOIUrl":"10.1016/j.tetlet.2024.155327","url":null,"abstract":"<div><div>The alkylation of tetrazole and acetone under the catalysis of TfOH has been shown to be an efficient process with high levels of regioselective control. This protocol features simple and readily accessible starting materials, unique reaction mechanism, excellent compatibility with diverse functional groups.</div></div>","PeriodicalId":438,"journal":{"name":"Tetrahedron Letters","volume":"151 ","pages":"Article 155327"},"PeriodicalIF":1.5,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142432879","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}
Two new isoledene-type sesquiterpenoids, 1 and 2, were isolated from an Okinawan soft coral Heteroxenia sp. The planar structures and stereochemistry of 1 and 2 were determined by spectroscopic analysis, X-ray crystallography, and comparison of experimental and calculated ECD studies. Antiviral and anti-leishmania assays were performed. Compound 2 exhibited activity against promastigotes of Leishmania major.
{"title":"Two isoledene-type sesquiterpenoids from a soft coral Heteroxenia sp.","authors":"Viqqi Kurnianda , Hao-Chun Hu , Ping-Jyun Sung , Yasuhiro Hayashi , Kanami Mori-Yasumoto , Ayumi Suetake , Hikari Nakayama , Mina Yasumoto-Hirose , Yuna Tsutsumi , Genta Koja , Yu-Chi Tsai , Takahiro Jomori , Junichi Tanaka","doi":"10.1016/j.tetlet.2024.155323","DOIUrl":"10.1016/j.tetlet.2024.155323","url":null,"abstract":"<div><div>Two new isoledene-type sesquiterpenoids, <strong>1</strong> and <strong>2</strong>, were isolated from an Okinawan soft coral <em>Heteroxenia</em> sp. The planar structures and stereochemistry of <strong>1</strong> and <strong>2</strong> were determined by spectroscopic analysis, X-ray crystallography, and comparison of experimental and calculated ECD studies. Antiviral and anti-leishmania assays were performed. Compound <strong>2</strong> exhibited activity against promastigotes of <em>Leishmania major</em>.</div></div>","PeriodicalId":438,"journal":{"name":"Tetrahedron Letters","volume":"151 ","pages":"Article 155323"},"PeriodicalIF":1.5,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142446919","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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