Xiaohan Jin , Na Gao , Bingwei Hu , Mei Chen , Yan Zheng , Bingfei Shi , Wenhui Ma , Yiren Xu , Jianqiang Zhang
{"title":"Metal-free regioselective ring expansion reaction of acenaphthenequinone with diazomethanes: A facile one-pot synthesis of phenalenones","authors":"Xiaohan Jin , Na Gao , Bingwei Hu , Mei Chen , Yan Zheng , Bingfei Shi , Wenhui Ma , Yiren Xu , Jianqiang Zhang","doi":"10.1016/j.tetlet.2025.155559","DOIUrl":"10.1016/j.tetlet.2025.155559","url":null,"abstract":"<div><div>Herein, we describe a regioselective ring-expansion reaction of acenaphthenequinone using N-tosylhydrazone as diazo 1,3-dipolar precursor, which can highly efficiently prepare functionalized 3-phenylphenalenones in ethanol solvent. These reactions feature readily available starting materials, transition metal- and oxidant-free, Ecofriendly operations, one-pot syntheses and wide functional group tolerance. Specifically, in the synthesized phenalenones, C-2 and C-3 are substituted by hydroxyl and phenyl has not been reported so far, and the potential biological and physical value of these newly synthesized corresponding products has good application foreground.</div></div>","PeriodicalId":438,"journal":{"name":"Tetrahedron Letters","volume":"162 ","pages":"Article 155559"},"PeriodicalIF":1.5,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143791444","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}
{"title":"Synthesis and PEGylation of a novel, per-6-substituted propargyl sulfonamide β-cyclodextrin","authors":"Thomas K. Green","doi":"10.1016/j.tetlet.2025.155592","DOIUrl":"10.1016/j.tetlet.2025.155592","url":null,"abstract":"<div><div>A novel single isomer, per-6-substituted alkyne-terminated sulfonamide β-cyclodextrin (β-CD) was synthesized, in two steps, from heptakis-2,3-<em>O</em>-dimethyl-6-O-sulfobutyl-β-CD, sodium salt. The intermediate sulfonamide β-CD was then per-6-PEGylated in a third step with azide-terminated polyethylene glycols (N<sub>3</sub>-PEG<sub>5</sub>-OH and N<sub>3</sub>-PEG<sub>47</sub>-OCH<sub>3</sub>) by copper-catalyzed azide-alkyne cycloaddition (CuAAC) The described derivatization strategy is the first to exploit the reactivity of sulfonate functions of sulfobutylether (SBE) anionic cyclodextrins, and results in a water-soluble, single isomer PEG-triazole-sulfonamide β-CD with an extended hydrophobic cavity.</div></div>","PeriodicalId":438,"journal":{"name":"Tetrahedron Letters","volume":"162 ","pages":"Article 155592"},"PeriodicalIF":1.5,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143821008","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}
{"title":"Microwave-assisted one-pot synthesis of fused isoxazolo[4′,5′:3,4]pyrrolo[1,2-c]pyrimidines as potent anticancer agents: In vitro and in silico study","authors":"Raveendar Reddy Thatikonda, Karuna Sree Merugu","doi":"10.1016/j.tetlet.2025.155570","DOIUrl":"10.1016/j.tetlet.2025.155570","url":null,"abstract":"<div><div>Microwave-aided one-pot synthesis of certain fused isoxazolo[4′,5′:3,4]pyrrolo[1,2-<em>c</em>] pyrimidine derivatives are synthesized using one-pot Cu(I)-catalyzed [3+2]cycloaddition, followed by Pd-catalyzed C<img>C bond coupling between iodoalkyne and freshly prepared nitrile oxides in a recyclable ionic liquid [Emim]BF<sub>4</sub>. The anticancer efficacy of the synthesized isoxazoles was then tested <em>in vitro</em> against A-459 and NCI-H460 cancer cell lines, and some compounds (<strong>5k</strong>–<strong>5n</strong>) demonstrated more activity than the others, with <strong>5k</strong> and <strong>5l</strong> acting more potently than the standard drugs, 5-FU and erlotinib. We also detected EGFR inhibitory activity in the potent compounds <strong>5k</strong>, <strong>5l</strong>, <strong>5m</strong>, and <strong>5n</strong>, and the results revealed that compound <strong>5m</strong> had the highest inhibitory action compared to the other compounds and was comparable to erlotinib. We also performed <em>in silico</em> tests to assess the molecular interactions of more powerful compounds with EGFR protein (PDB: <span><span>4HJO</span><svg><path></path></svg></span>). Our findings indicated that all potent compounds had stronger binding interactions than standard erlotinib (−7.69 kcal/mol), with binding energies ranging from −8.41 to −9.26 kcal/mol.</div></div>","PeriodicalId":438,"journal":{"name":"Tetrahedron Letters","volume":"162 ","pages":"Article 155570"},"PeriodicalIF":1.5,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143791403","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}
{"title":"Syntheses of C22–C29 and C20–C29 sections of amphidinol 3","authors":"Yuki Yamashita, Yuma Wakamiya, Yusuke Mita, Yoko Yasuno, Tohru Oishi","doi":"10.1016/j.tetlet.2025.155586","DOIUrl":"10.1016/j.tetlet.2025.155586","url":null,"abstract":"<div><div>Polyol segments corresponding to C22–C29 and C20–C29 sections of amphidinol 3 (AM3) were synthesized as building blocks of artificial analogues of AM3 for structure–activity relationship studies. The C22–C29 section was synthesized from (<em>S</em>)-Roche ester through continuous half-reduction of an ester and a Grignard reaction under flow and batch conditions, followed by iterative ozonolysis and Grignard reactions. The C20–C29 section was derived from the common intermediate of AM3 and the artificial analogue corresponding to the C21–C67 section via olefination and Sharpless asymmetric dihydroxylation.</div></div>","PeriodicalId":438,"journal":{"name":"Tetrahedron Letters","volume":"162 ","pages":"Article 155586"},"PeriodicalIF":1.5,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143826258","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}
{"title":"Bis-dispiro-indolinone-pyrrolidine-imidazolones with polymethylene linkers between imidazolone fragments","authors":"V.S. Polyakov, E.V. Pervakova, Yu.K. Grishin, E.K. Beloglazkina","doi":"10.1016/j.tetlet.2025.155589","DOIUrl":"10.1016/j.tetlet.2025.155589","url":null,"abstract":"<div><div>A method for the synthesis of bis-(dispiro-imidazolone-pyrrolidine-indolinones) in which spirocyclic fragments are linked by C4, C6 and C8 alkyl linkers between the N(3) nitrogen atoms of the imidazolone ring has been proposed. A two-step synthetic sequence was used for the synthesis, consisting of the interaction of α,ω-dialkylamines with ethyl isothiocyanatoacetate, followed by the reaction of the intermediate bis-thioureas with substituted benzaldehydes to produce bis-arylidenetiohydantoins and the final 1,3-dipolar cycloaddition of azomethine ylides generated in situ from isatins and <em>N</em>-methylglycine.</div></div>","PeriodicalId":438,"journal":{"name":"Tetrahedron Letters","volume":"162 ","pages":"Article 155589"},"PeriodicalIF":1.5,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143807141","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}
{"title":"Alkylidene transfer reactions from nitrones to iminoiodanes","authors":"Noriko Okamoto, Haruto Ogino, Takuya Sueda","doi":"10.1016/j.tetlet.2025.155558","DOIUrl":"10.1016/j.tetlet.2025.155558","url":null,"abstract":"<div><div>Herein, we report a reaction involving alkylidene transfer from nitrones to iminoiodanes. The alkylidene moiety is transferred from the nitrone to the imido group of the iminoiodane accompanied by cleavage of the nitrone C<img>N bond to deliver a nitroso compound and an imine. When an excess of the iminoiodane is used at higher temperature, the iminoiodane reacts with the nitroso compound to form an azoxy sulfone. We also found that an azomethine imine can be used as an alkylidene transfer agent.</div></div>","PeriodicalId":438,"journal":{"name":"Tetrahedron Letters","volume":"161 ","pages":"Article 155558"},"PeriodicalIF":1.5,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143768829","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}
Mohsen Teimouri, Mahshid Attarroshan, Bruno Donnadieu, Sean L. Stokes, Joseph P. Emerson
{"title":"Copper(II) NHC pincer complexes containing 1,2,3-triazole units: Synthesis, structure and catalysis for CN bond forming reactions","authors":"Mohsen Teimouri, Mahshid Attarroshan, Bruno Donnadieu, Sean L. Stokes, Joseph P. Emerson","doi":"10.1016/j.tetlet.2025.155588","DOIUrl":"10.1016/j.tetlet.2025.155588","url":null,"abstract":"<div><div>Two new tridentate copper(II) <em>N</em>-heterocyclic carbene (NHC) pincer complexes with triazolyl donor groups, L2, [TrzmPymBI][PF<sub>6</sub>] and L3, [bTrzmBI][PF<sub>6</sub>], were synthesized and characterized by X-ray single crystal analysis and elemental analysis. The 5-coordinate τ value shows distorted square pyramidal geometry for both complexes. These copper(II)-NHC complexes exhibited excellent catalytic activity (95–100 % conversion) for N<img>H insertion reactions toward the formation of new N<img>C bonds between aniline and methyl phenyldiazoacetate. Under optimized conditions, the catalyst was screened against 22 different aniline derivatives and achieved high conversion (65–100 %) toward both electron-donating and electron-withdrawing functional groups on the amine substrates, while limiting self-coupling of activated diazo compounds. The substrate scope study revealed that steric hindrance and basicity are key factors influencing reactivity. Secondary and aliphatic amines showed weak reactivity. Moreover, the utility of this catalyst was demonstrated through a gram-scale synthesis of a diarylhydantoin, a class of compound known to act as a COX-2 inhibitor. These results highlight the versatility and efficiency of copper(II)-NHC complexes in facilitating selective carbene insertions and provide a promising approach for the synthesis of valuable nitrogen-containing compounds.</div></div>","PeriodicalId":438,"journal":{"name":"Tetrahedron Letters","volume":"162 ","pages":"Article 155588"},"PeriodicalIF":1.5,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143826250","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}
{"title":"Development of Fmoc-O-N(CH₃)-Bz as a novel Fmoc protecting reagent for the preparation of various Fmoc-protected amino acids.","authors":"Yu Zhao, Boquan Ren, Junfeng Peng, Jiajun Chen, Feng Yang, Qing Li, Yan-Jun Xu","doi":"10.1016/j.tetlet.2025.155587","DOIUrl":"10.1016/j.tetlet.2025.155587","url":null,"abstract":"<div><div>A novel series of Fmoc-O-N(CH₃)-sulfonyl/acyl protecting reagents was developed to overcome challenges associated with the formation of Fmoc-β-Ala-OH via the Lossen rearrangement, a limitation of commonly used Fmoc-OSu reagents. These reagents were efficiently synthesized from the cost-effective and commercially available starting material, <em>N</em>-methylhydroxylamine hydrochloride. Fmoc-O-N(CH₃)-Bz was identified as the optimal Fmoc reagent, providing the highest reaction yields under optimized mild conditions. Additionally, Fmoc-O-N(CH₃)-Bz demonstrated versatility in synthesizing a wide range of Fmoc-protected amino acids with moderate to excellent yields, with yields ranging from 70 % to 93 % for cyclic amino acids.</div></div>","PeriodicalId":438,"journal":{"name":"Tetrahedron Letters","volume":"162 ","pages":"Article 155587"},"PeriodicalIF":1.5,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143817380","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}
Hoang V.M. Trinh , Vu H. Luu , Kien Q. Truong , Khoa H.D. Nguyen , Tuong Q. Le , Tung T. Nguyen , Duyen K. Nguyen
{"title":"Three-component cyclization of 2-chloronitrobenzenes, sulfoxonium ylides, and elemental sulfur","authors":"Hoang V.M. Trinh , Vu H. Luu , Kien Q. Truong , Khoa H.D. Nguyen , Tuong Q. Le , Tung T. Nguyen , Duyen K. Nguyen","doi":"10.1016/j.tetlet.2025.155574","DOIUrl":"10.1016/j.tetlet.2025.155574","url":null,"abstract":"<div><div>Synthesis of 2-acyl benzothiazoles from substituted nitroarenes as the starting material is rare. Herein we report a method to allow for the coupling of 2-chloronitrobenzene derivatives, substituted sulfoxonium ylides, and elemental sulfur to afford 2-acyl benzothiazoles. Studies regarding scope of functionalities revealed that protected phenol, dimethylamino, and heterocycles groups could be tolerated. That both aryl and alkyl sulfoxonium ylides were competent substrates overcome the current limitation in yielding 2-acyl benzothiazoles from 2-halonitroarenes.</div></div>","PeriodicalId":438,"journal":{"name":"Tetrahedron Letters","volume":"162 ","pages":"Article 155574"},"PeriodicalIF":1.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143791445","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}
{"title":"Thermohexins A and B, two new hexacyclicpeptides from marine algae-derived Streptomyces thermolineatus NAK03196","authors":"Guo Dong Zhang , Cheng Yuan Yuan , Ling Jiao Zou, Bo Zhang, Rui Hua Jiao","doi":"10.1016/j.tetlet.2025.155565","DOIUrl":"10.1016/j.tetlet.2025.155565","url":null,"abstract":"<div><div>This study describes the isolation and structural elucidation of two new hexacyclic peptides, thermohexins A (<strong>1</strong>) and B (<strong>2</strong>), from the fermentation broth of the marine algae-associated bacterium <em>Streptomyces thermolineatus</em> NAK03196. Their structures were determined using high-resolution electrospray ionization mass spectrometry (HR-ESI-MS), tandem mass spectrometry (MS/MS), nuclear magnetic resonance (NMR) spectroscopy, and the modified Marfey's method. Genomic analysis revealed that tyrohexins are biosynthesized via a nonribosomal peptide synthetase (NRPS) pathway and undergo macrocyclization mediated by a penicillin-binding protein-like thioesterase.</div></div>","PeriodicalId":438,"journal":{"name":"Tetrahedron Letters","volume":"161 ","pages":"Article 155565"},"PeriodicalIF":1.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143739084","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}