Beilstein Journal of Organic Chemistry最新文献

{"title":"Cone <i>p</i>-aminocalix[4]arenes enriched with 'clickable' alkyne or azide functionalities.","authors":"Ilia Korniltsev, Vasily Bazhenov, Alexander Gorbunov, Dmitry Cheshkov, Stanislav Bezzubov, Vladimir Kovalev, Ivan Vatsouro","doi":"10.3762/bjoc.22.28","DOIUrl":"10.3762/bjoc.22.28","url":null,"abstract":"<p><p>Efficient approaches have been developed for the synthesis of heteromultifunctional cone calix[4]arenes containing four amino groups at the wide rim and one, two or four propargyl or 2-azidoethyl groups at the narrow rim of the macrocycle, which can be used for expanding functionalization of the calixarene core in the well-known amine acylation (or similar reactions) and CuAAC 'click' reactions. Two different strategies were implemented to obtain propargylated and 2-azidoethylated <i>p</i>-aminocalixarenes. In the case of propargylated calixarenes, sterically crowding silyl protection was introduced into the alkyne groups of <i>p-tert</i>-butylcalix[4]arene (multiple) propargyl ethers, and the resulting compounds were <i>ipso</i>-nitrated followed by reduction of the nitro groups. To prepare 2-azidoethylated macrocycles, the <i>ipso</i>-nitration/reduction sequence was applied to <i>p-tert</i>-butylcalix[4]arenes containing 2-tosyloxyethyl groups at the narrow rims followed by replacement of the tosyloxy groups with azide ones. In all cases, <i>p</i>-aminocalix[4]arenes were obtained as the readily cleavable <i>tert</i>-butoxycarbonyl (Boc) derivatives, which was crucial for certain transformation and purification steps. To confirm the functionalization capabilities of the five obtained multifunctional calixarenes, they were reacted with excess benzyl azide or phenylacetylene, taken as representatives, under copper(I) catalysis, resulting in the narrow-rim triazolated macrocycles. By removing the Boc protecting groups and involving the free amino groups in reactions with <i>p</i>-tolyl isocyanate, a series of narrow-rim triazolated tetraureacalix[4]arenes was obtained. Examination of the ¹H NMR spectra of the tetraureas in CDCl₃ showed that in most cases triazole heterocycles do not intervene the formation of homo- and heterodimeric capsules by these compounds. Thus, considering the synthetic value of CuAAC and amine transformations, <i>p</i>-aminocalix[4]arenes enriched with alkyne or azide functionalities can be readily used as multifunctional platforms to obtain even higher functionalized macrocycles. As an example, they can be used for the preparation of sophisticated supramolecular assemblies with homo- or heterodimeric calixarene cores and virtually any functional units attached to them via triazole groups.</p>","PeriodicalId":8756,"journal":{"name":"Beilstein Journal of Organic Chemistry","volume":"22 ","pages":"399-415"},"PeriodicalIF":2.7,"publicationDate":"2026-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12990471/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147472446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design, synthesis and biological evaluation of 2,5-diaryloxazolo[4,5-<i>d</i>]pyrimidin-7-ylamines as selective cytotoxic agents against HeLa cells.","authors":"Maryna V Kachaeva, Agnieszka B Olejniczak, Marta Denel-Bobrowska, Victor V Zhirnov, Yevheniia S Velihina, Stepan G Pilyo, Volodymyr S Brovarets","doi":"10.3762/bjoc.22.27","DOIUrl":"10.3762/bjoc.22.27","url":null,"abstract":"<p><p>Nine novel functionalized 2,5-diaryloxazolo[4,5-<i>d</i>]pyrimidin-7-ylamines were designed, synthesized and characterized using ¹H, ¹³C NMR, IR spectroscopy, elemental analysis, and liquid chromatography-mass spectrometry<i>.</i> Their anticancer activity was assessed against human cancer cell as well as non-cancer cell lines. Three compounds, <b>1</b>, <b>3</b>, and <b>9</b>, were the most cytotoxic to HeLa cells (IC₅₀ = 6.13 ± 1.95, 13.99 ± 1.80 and 49.92 ± 3.98 μM, respectively). However, only compounds <b>1</b>, <b>7</b>, and <b>9</b> were selective against the tested lines. Compound <b>9</b> can be classified as the most attractive and promising candidate for further development against cervical adenocarcinoma.</p>","PeriodicalId":8756,"journal":{"name":"Beilstein Journal of Organic Chemistry","volume":"22 ","pages":"390-398"},"PeriodicalIF":2.7,"publicationDate":"2026-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12973442/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147430637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dialkylaminoalkylation of β-ketosulfones via ring-opening of 3-sulfonylpyrrolidines.","authors":"Evgeny M Buev, Alexander V Pavlushin, Vladimir S Moshkin, Vyacheslav Y Sosnovskikh","doi":"10.3762/bjoc.22.26","DOIUrl":"10.3762/bjoc.22.26","url":null,"abstract":"<p><p>Herein, a three-step method for the simultaneous dialkylaminoethylation and heteromethylation of active methylene β-ketosulfones, promoted by a leaving benzoyl group, is proposed. The primary domino reaction of sarcosine, paraformaldehyde, and β-ketosulfones affords 3-sulfonyl-3-benzoylpyrrolidines in good to high yields. Further treatment with alkyl halides and heating of the quaternary ammonium salt in the presence of a O-, S- or N-nucleophile with cesium carbonate leads to a retro-Claisen reaction, ring-opening and Michael addition. The resulting novel 4-Nu-3-sulfonylbutan-1-amines are isolated in moderate to excellent overall yields. The reduction of the obtained products with LiAlH₄ leads to a substitution of the attached nucleophilic moiety with hydrogen in good yields.</p>","PeriodicalId":8756,"journal":{"name":"Beilstein Journal of Organic Chemistry","volume":"22 ","pages":"383-389"},"PeriodicalIF":2.7,"publicationDate":"2026-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12973443/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147429602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Electrosynthetic access to unsymmetrical oxaza[8]helicenes with high chiral stability and strong circularly polarized luminescence (CPL).","authors":"Tin Zar Aye, Rubal Sharma, Muthu Karuppasamy, Daiya Suzuki, Haruka Nakajima, Yoshitane Imai, Mitsuhiro Arisawa, Mohamed S H Salem, Shinobu Takizawa","doi":"10.3762/bjoc.22.25","DOIUrl":"10.3762/bjoc.22.25","url":null,"abstract":"<p><p>Heterohelicenes are compelling chiral π-conjugated scaffolds for optoelectronic and chiral-photonic technologies because their helical frameworks and doped heteroatoms endow them with various photophysical, chiroptical, and electronic merits. However, unsymmetrical heterohelicenes remain rare, as their synthesis is often hindered by chemoselectivity and regioselective control. Here, we exploit the differential redox potentials of two coupling partners as a key player to achieve a chemo- and regioselective electrosynthetic access to a new family of unsymmetrical oxaza[8]helicenes. A controlled anodic sequence enables selective oxidative hetero-coupling followed by dehydrative cyclization, furnishing the extended [8]helical scaffold efficiently under mild, oxidant-free conditions. Structural analyses show retained aromaticity, increased helical distortion, and higher configurational stability (≈38 kcal/mol) relative to their oxaza[7]helicene analogues (<25 kcal/mol). After chiral HPLC separation, the enantiomers display mirror-image CD and strong solution CPL, with |<i>g</i> <i>_lum</i> | up to 2.6 × 10^-3 and fluorescence brightness up to 30.75 M^-1 cm^-1.</p>","PeriodicalId":8756,"journal":{"name":"Beilstein Journal of Organic Chemistry","volume":"22 ","pages":"372-382"},"PeriodicalIF":2.7,"publicationDate":"2026-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12951319/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147347119","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Non-central chirality in organic chemistry.","authors":"Ken Tanaka, Naohiko Yoshikai","doi":"10.3762/bjoc.22.24","DOIUrl":"https://doi.org/10.3762/bjoc.22.24","url":null,"abstract":"","PeriodicalId":8756,"journal":{"name":"Beilstein Journal of Organic Chemistry","volume":"22 ","pages":"370-371"},"PeriodicalIF":2.1,"publicationDate":"2026-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12951317/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147347172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recent advances in the cleavage of non-activated amides.","authors":"Eun-Sol Choi, Hyo-Jun Lee","doi":"10.3762/bjoc.22.23","DOIUrl":"10.3762/bjoc.22.23","url":null,"abstract":"<p><p>The amide bond is one of the most fundamental and widely utilized functional groups in organic chemistry, central to the structures of pharmaceuticals, bioactive molecules, and advanced materials. However, its exceptional resonance stabilization renders the C-N bond highly inert, posing a persistent synthetic challenge for its transformation. While twisted amides with distorted C-N bonds have offered useful reactivity enhancements, the selective activation of conventional, non-activated amides remains far more difficult. This review summarizes recent advances over the past decade in the activation and cleavage of non-activated amide C-N bonds for their conversion into diverse carboxylic acid derivatives. Key strategies covered include transition-metal catalysis, electrophilic activation, strong base-counter-cation systems, and <i>N</i>-based activating groups that enable chemoselective bond cleavage. Together, these developments provide powerful tools for amide functionalization and offer new opportunities for efficient, practical, and selective syntheses.</p>","PeriodicalId":8756,"journal":{"name":"Beilstein Journal of Organic Chemistry","volume":"22 ","pages":"352-369"},"PeriodicalIF":2.7,"publicationDate":"2026-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12927485/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147282183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis of tricyclic fused pyrrolidine nitroxides from 2-alkynylpyrrolidine-1-oxyls.","authors":"Mark M Gulman, Yuliya F Polienko, Sofia Yu Trakhininа, Yuri V Gatilov, Tatyana V Rybalova, Sergey A Dobrynin, Igor A Kirilyuk","doi":"10.3762/bjoc.22.22","DOIUrl":"10.3762/bjoc.22.22","url":null,"abstract":"<p><p>Rotational correlation time is a key parameter for organic radical contrast agents (ORCA) for magnetic resonance imaging (MRI). Design of polycyclic systems with incorporated nitroxide moieties in which rotation of the radical separately from the framework is impossible is one of the ways to improve properties of ORCA. Feasibility of the synthesis of rigid 3b,4,5,6,6a,7-hexahydropyrrolo[2',3':3,4]pyrrolo[1,2-<i>c</i>][1,2,3]triazole and 3b,4,5,6,6a,7-hexahydropyrrolo[2',3':3,4]pyrrolo[1,2-<i>b</i>]pyrazole ring systems with incorporated nitroxide moiety from 2-alkynyl-substituted pyrrolidine nitroxides was studied. These nitroxides have been prepared via intramolecular Huisgen cycloaddition or intramolecular alkylation in 2-pyrazolyl derivatives prepared by Michael addition-cyclocondensation of the corresponding alkynones with hydrazine. The reduction kinetics by ascorbate showed that the formation of the rigid tricyclic framework does not lead to a significant increase in stability of the radical center to chemical reduction.</p>","PeriodicalId":8756,"journal":{"name":"Beilstein Journal of Organic Chemistry","volume":"22 ","pages":"344-351"},"PeriodicalIF":2.7,"publicationDate":"2026-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12927486/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147282170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spirobarbiturates with a pyrrolizidine moiety: synthesis, structure and biological evaluation.","authors":"Arthur A Puzyrkov, Andrew S Drachuk, Ekaterina A Popova, Alexander V Stepakov, Vitali M Boitsov","doi":"10.3762/bjoc.22.20","DOIUrl":"10.3762/bjoc.22.20","url":null,"abstract":"<p><p>Polycyclic spirobarbiturates containing a pyrrolizidine moiety were synthesized via a one-pot three-component 1,3-dipolar cycloaddition reaction of alloxan, ʟ-proline and <i>N</i>-substituted maleimides. The reaction stereoselectivity was found to depend on the nature of substituents in the maleimide: in most cases the <i>endo</i>-isomer is the main (or only) product, but for some <i>N</i>-arylmaleimides the <i>exo</i>-product is predominant. The proposed mechanism is discussed, and the products were characterized by detailed spectral analysis. The configuration of the stereocenters was determined by X-ray diffraction analysis (XRD) for two adducts, followed by Hirshfeld surface analysis. The antiproliferative effect of the synthesized compounds against cancer cell lines was assessed.</p>","PeriodicalId":8756,"journal":{"name":"Beilstein Journal of Organic Chemistry","volume":"22 ","pages":"274-288"},"PeriodicalIF":2.7,"publicationDate":"2026-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12927484/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147282190","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ring contraction and ring expansion reactions in terpenoid biosynthesis and their application to total synthesis.","authors":"Nicolas Kratena, Nicolas Heinzig, Peter Gärtner","doi":"10.3762/bjoc.22.21","DOIUrl":"10.3762/bjoc.22.21","url":null,"abstract":"<p><p>Terpenoids exhibit remarkable structural diversity, including highly complex ring-expanded or contracted carbocyclic skeletons. This review aims to explore intriguing examples of such ring-size alterations in all aspects of terpenoid synthesis. The current state-of-the-art regarding proposed biosynthetic pathways for terpenoids with unusual carbon skeleta, occurring either during initial cyclisation or subsequent oxidative tailoring, will be examined and discussed. Where possible, biogenetic relationships of closely related families of natural products will be contextualised by showing the mechanistic rationale for their interconversion. In the second part of this article, the application of bioinspired ring contraction and ring-expansion strategies in relevant natural product syntheses will be presented, demonstrating how synthetic chemistry can help to elucidate plausible biogenetic routes for structurally complex natural products.</p>","PeriodicalId":8756,"journal":{"name":"Beilstein Journal of Organic Chemistry","volume":"22 ","pages":"289-343"},"PeriodicalIF":2.7,"publicationDate":"2026-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12927490/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147282116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A mild and atom-efficient four-component cascade strategy for the construction of biologically relevant 4-hydroxyquinolin-2(1<i>H</i>)-one derivatives.","authors":"Dmitrii A Grishin, Kseniia I Sharkovskaia, Ilya G Kolmakov, Daria A Ipatova, Rostislav A Petrov, Nikolai D Dagaev, Dmitry A Skvortsov, Maria G Khrenova, Valeriy V Andreychev, Sergei A Evteev, Yan A Ivanenkov, Roman L Antipin, Olga А Dontsova, Elena K Beloglazkina","doi":"10.3762/bjoc.22.18","DOIUrl":"10.3762/bjoc.22.18","url":null,"abstract":"<p><p>A mild and atom-economical four-component cascade reaction has been developed, enabling the efficient and selective synthesis of previously inaccessible 4-hydroxyquinolin-2(1<i>H</i>)-one derivatives. Utilizing readily available 6-halo-4-hydroxyquinolinones, aromatic aldehydes, Meldrum's acid, and alcohols under ʟ-proline catalysis, the reaction proceeds via in situ formation of arylidene-substituted Meldrum acids followed by sequential Michael-type addition and subsequent cascade transformations. This versatile one-pot protocol delivers structurally diverse open-chain 3-arylpropanoate esters in moderate to good yields (46-69%), while cyclic pyranoquinolinones are formed under kinetically controlled conditions. Subsequent transformations afford isopropyl and cyclohexyl analogues via hydrolysis-esterification. A preliminary biological evaluation revealed low cytotoxicity and modest antibacterial activity against <i>Escherichia coli</i> ΔtolC strains. This sustainable synthetic approach constitutes the first direct access to scarcely explored open-chain quinolinone esters, expanding the medicinal chemistry toolbox with promising scaffolds for drug discovery.</p>","PeriodicalId":8756,"journal":{"name":"Beilstein Journal of Organic Chemistry","volume":"22 ","pages":"244-256"},"PeriodicalIF":2.7,"publicationDate":"2026-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12908358/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146212047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}