Beilstein Journal of Organic Chemistry最新文献

{"title":"Structural reassignment of compound 968, an allosteric glutaminase inhibitor.","authors":"Lindsey A Albertelli, Sainabou Jallow, Chun Li, Scott M Ulrich","doi":"10.3762/bjoc.22.33","DOIUrl":"https://doi.org/10.3762/bjoc.22.33","url":null,"abstract":"<p><p>Many cancer cells require extracellular glutamine to meet the energetic, biosynthetic, and redox demands of the proliferative state. Glutaminases catalyze the hydrolysis of glutamine to glutamate, which supports the biosynthesis of amino acids, lipids, and glutathione and can also be oxidatively deaminated to α-ketoglutarate and enter the citric acid cycle. The \"glutamine addiction\" of cancer cells has made glutaminase an attractive anticancer drug target. Compound 968 is a glutaminase inhibitor that is widely used to probe cancer cells' dependence on glutaminase activity. Here, we show by NMR spectroscopy and X-ray crystallography that the reported benzo[<i>c</i>]phenanthridine structure of compound 968 is incorrect; its true structure is the isomeric benzo[<i>c</i>]acridine. The structural reassignment of compound 968 will aid the medicinal chemistry development of this important compound.</p>","PeriodicalId":8756,"journal":{"name":"Beilstein Journal of Organic Chemistry","volume":"22 ","pages":"455-460"},"PeriodicalIF":2.1,"publicationDate":"2026-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12990460/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147472365","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":"Concept-driven strategies in target-oriented synthesis.","authors":"David Yu-Kai Chen, Chao Li, Yefeng Tang","doi":"10.3762/bjoc.22.32","DOIUrl":"https://doi.org/10.3762/bjoc.22.32","url":null,"abstract":"","PeriodicalId":8756,"journal":{"name":"Beilstein Journal of Organic Chemistry","volume":"22 ","pages":"451-454"},"PeriodicalIF":2.1,"publicationDate":"2026-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12990437/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147472409","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 facile and practical method for the synthesis of <i>trans</i>-(±)-taxifolin and its derivatives via Darzens reaction.","authors":"Bo Peng, Panpan Yang, Maaz Khan, Xiaotong Lin, Jiang Wu, Peng Fu, Qingqing Wu","doi":"10.3762/bjoc.22.31","DOIUrl":"https://doi.org/10.3762/bjoc.22.31","url":null,"abstract":"<p><p>The synthesis of racemic <i>trans</i>-taxifolin (<i>trans</i>-(±)-taxifolin) and its derivatives and subsequent chiral separation is the most prevalent chemical method to obtain enantiomerically pure taxifolin and its derivatives. The development of an economical and practical synthetic route to <i>trans</i>-(±)-taxifolin, a key precursor to the enantiomerically pure <i>trans</i>-taxifolin, is therefore of great importance and significance. In this work, we developed a new synthetic method for <i>trans</i>-(±)-taxifolin and its derivatives with 2,4,6-trihydroxyacetophenone as a starting material undergoing hydroxy protection, α-bromination, construction of α,β-epoxy carbonyl products via the Darzens reaction, acid-mediated deprotection, and cyclization to afford the target compounds. This method is highlighted by satisfactory overall yields (20-41%) and proceeds without the use of explosive peroxides (such as H₂O₂), which are commonly employed in methods reported earlier. The avoidance of explosive peroxides in the present method enables safe operation, easy scale-up, and also the synthesis of taxifolin derivatives with oxidant-sensitive groups, largely expanding the substituent scope compared with the previous method.</p>","PeriodicalId":8756,"journal":{"name":"Beilstein Journal of Organic Chemistry","volume":"22 ","pages":"443-450"},"PeriodicalIF":2.1,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12990444/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147472391","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 and stereochemical analysis of dynamic planar chiral oxa[7]orthocyclophene.","authors":"Yukiho Hashimoto, Yuuya Kawasaki, Kazunobu Igawa, Katsuhiko Tomooka","doi":"10.3762/bjoc.22.30","DOIUrl":"https://doi.org/10.3762/bjoc.22.30","url":null,"abstract":"<p><p>Planar chiral C6-substituted oxa[7]orthocyclophenes were designed and synthesized, and their stereochemical behavior was analyzed. The Kumada-Tamao coupling of the C6-iodo-substituted oxacyclophene enabled the efficient and divergent synthesis of C6-substituted derivatives. The stereochemical analysis of the oxacyclophenes revealed that the iodo- and methyl-substituted derivatives have reasonable stereochemical stability. The planar chirality of the methyl-substituted oxacyclophene was successfully transformed into central chirality by epoxidation without loss of enantiomeric purity.</p>","PeriodicalId":8756,"journal":{"name":"Beilstein Journal of Organic Chemistry","volume":"22 ","pages":"436-442"},"PeriodicalIF":2.1,"publicationDate":"2026-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12990439/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147472525","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 and anti-cancer activity of naphthalimide-organylselanyl conjugates.","authors":"Rajkumar Ravi, Selvakumar Karuthapandi","doi":"10.3762/bjoc.22.29","DOIUrl":"https://doi.org/10.3762/bjoc.22.29","url":null,"abstract":"<p><p>The structure-based approach remains a valuable tool for rapid and high-throughput drug discovery and lead optimisation. In this study, we report the in-silico modelling and anticancer activity of two 1,8-napthalimide (NAP) derivatives containing organyl selanyl groups. The organylselanyl function <i>n</i>-octylselanyl (<i>n</i>-OctSe) or phenylselanyl (PhSe) was introduced at the 6-position of a naphthalimide structure having a conserved 3-(4-(<i>tert</i>-butyl)phenoxy)propyl function at the imide nitrogen. The resultant naphthalimide-organylselanyl conjugates, NAP-SePh and NAP-Se(<i>n</i>-Oct), were characterised using various spectroscopic techniques, including FTIR, ¹H, ¹³C, ⁷⁷Se NMR and high-resolution mass spectrometry (HRMS). NAP-SePh was structurally characterised by single-crystal X-ray diffraction analysis. The anticancer potential of the NAP-SePh and NAP-Se(<i>n</i>-Oct) was evaluated using an in vitro cell viability assay with MDA-MB-231 triple-negative breast cancer (TNBC) cells. The IC₅₀ values for compounds NAP-SePh and NAP-Se(<i>n</i>-Oct) were 27.92 ± 3 µM and 23.06 ± 3 μM, respectively. Molecular docking simulations revealed that NAP-SePh and NAP-Se(<i>n</i>-Oct) show binding affinities of -10.39 and -8.53 kcal/mol for the (1M17) active, and -10.66 and -10.59 kcal/mol for the (4HJO) inactive conformation of the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) in which erlotinib, a well-known anticancer drug, binds.</p>","PeriodicalId":8756,"journal":{"name":"Beilstein Journal of Organic Chemistry","volume":"22 ","pages":"416-435"},"PeriodicalIF":2.1,"publicationDate":"2026-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12990455/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147472363","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":"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":"https://doi.org/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":2.1,"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":"https://doi.org/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":2.1,"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":"https://doi.org/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":2.1,"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":"https://doi.org/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":2.1,"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}