Beilstein Journal of Organic Chemistry最新文献_第8页

Hydrogen production from formic acid catalyzed by NHC-Cu complexes. NHC-Cu配合物催化甲酸制氢。

IF 2.7 4区化学

Beilstein Journal of Organic Chemistry Pub Date : 2026-04-23 eCollection Date: 2026-01-01 DOI: 10.3762/bjoc.22.48

Orlando Santoro, Catherine S J Cazin

引用次数: 0

Towards the targeted protein degradation of CK2: design and synthesis of CAM4066-based PROTACs. CK2靶向蛋白降解研究：基于cam4066的PROTACs的设计与合成

IF 2.7 4区化学

Beilstein Journal of Organic Chemistry Pub Date : 2026-04-22 eCollection Date: 2026-01-01 DOI: 10.3762/bjoc.22.47

Sophie Day-Riley, Sona Krajcovicova, Aryaman Raj Sokhal, Jan L Venne, Paul Brear, Marko Hyvönen, Benjamin C Whitehurst, Jason S Carroll, David R Spring

{"title":"Towards the targeted protein degradation of CK2: design and synthesis of CAM4066-based PROTACs.","authors":"Sophie Day-Riley, Sona Krajcovicova, Aryaman Raj Sokhal, Jan L Venne, Paul Brear, Marko Hyvönen, Benjamin C Whitehurst, Jason S Carroll, David R Spring","doi":"10.3762/bjoc.22.47","DOIUrl":"10.3762/bjoc.22.47","url":null,"abstract":"Human protein kinase CK2 is a constitutively active serine/threonine kinase implicated in numerous cancers. Although ATP-competitive inhibitors such as CX-4945 show therapeutic potential, they are limited by off-target effects and incomplete or transient CK2 suppression. PROTACs offer an alternative strategy by inducing proteasome-mediated degradation, with potential advantages in potency, selectivity, and duration of action. Herein, a series of CK2-targeting PROTACs has been designed and synthesised. By conjugating a CAM4066-derived warhead to CRBN or VHL ligands, four VHL-recruiting PROTACs, were prepared using PEG and alkyl linkers, alongside two CRBN-recruiting analogues featuring constrained linkers. A ligand-linker analogue in which a linker is projected from the solvent-exposed region of CK2α retained binding affinity comparable to CAM4066, confirming that linker installation is tolerated and preserves key interactions in the αD and ATP sites.","PeriodicalId":8756,"journal":{"name":"Beilstein Journal of Organic Chemistry","volume":"22 ","pages":"611-619"},"PeriodicalIF":2.7,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13159317/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147925952","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}

引用次数: 0

Regioselective approach to 5-arylsulfonylisoxazoles and their antimicrobial activity. 5-芳基磺酰基异恶唑的区域选择性研究及其抑菌活性。

IF 2.7 4区化学

Beilstein Journal of Organic Chemistry Pub Date : 2026-04-17 eCollection Date: 2026-01-01 DOI: 10.3762/bjoc.22.45

Artem S Sazonov, Dmitry A Vasilenko, Denis V Porfiriev, Yuri K Grishin, Rimma A Gazzaeva, Alisa P Chernyshova, Maxim A Kryakvin, Anna A Baranova, Vera A Alferova, Elena B Averina

{"title":"Regioselective approach to 5-arylsulfonylisoxazoles and their antimicrobial activity.","authors":"Artem S Sazonov, Dmitry A Vasilenko, Denis V Porfiriev, Yuri K Grishin, Rimma A Gazzaeva, Alisa P Chernyshova, Maxim A Kryakvin, Anna A Baranova, Vera A Alferova, Elena B Averina","doi":"10.3762/bjoc.22.45","DOIUrl":"10.3762/bjoc.22.45","url":null,"abstract":"This study presents a novel regioselective synthesis of 3-electron-withdrawing-group-(EWG)-substituted 5-sulfonyl- and 5-sulfinylisoxazoles from 3-EWG-5-nitroisoxazoles via nucleophilic aromatic substitution with thiophenols followed by oxidation with m-chloroperbenzoic acid (mCPBA). The scope of the reactions was explored, demonstrating high yields across a variety of functional groups and substituents. Optimized conditions enabled selective oxidation of thioaryl groups to sulfonyl or sulfinyl derivatives. Biological evaluation revealed that several compounds, especially 3-nitro-5-sulfonyl- and 5-sulfinylisoxazoles, exhibit potent antimicrobial activity against Gram-positive bacteria, fungi, and notably low MICs comparable to those of standard drugs. The mechanism of action studies indicate that these compounds induce the bacterial SOS response without inhibiting DNA synthesis-related enzymes such as DNA polymerase I, DNA gyrase, or topoisomerases I and IV, suggesting activation via bacterial reductases. These findings highlight the potential of these isoxazole derivatives as promising antimicrobial agents and provide new insights into their mechanism of action.","PeriodicalId":8756,"journal":{"name":"Beilstein Journal of Organic Chemistry","volume":"22 ","pages":"592-602"},"PeriodicalIF":2.7,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13159296/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147925875","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}

引用次数: 0

Computational prediction of C-H hydricities and their use in predicting the regioselectivity of electron-rich C-H functionalisation reactions. 碳氢化合物水合性的计算预测及其在预测富电子碳氢化合物功能化反应区域选择性中的应用。

IF 2.7 4区化学

Beilstein Journal of Organic Chemistry Pub Date : 2026-04-17 eCollection Date: 2026-01-01 DOI: 10.3762/bjoc.22.46

Rasmus M Borup, Nicolai Ree, Jan H Jensen

{"title":"Computational prediction of C-H hydricities and their use in predicting the regioselectivity of electron-rich C-H functionalisation reactions.","authors":"Rasmus M Borup, Nicolai Ree, Jan H Jensen","doi":"10.3762/bjoc.22.46","DOIUrl":"10.3762/bjoc.22.46","url":null,"abstract":"We present HAlator, a fully automated quantum chemistry (QM) workflow for computing C-H hydricities and explore its potential in predicting the regioselectivity of electron-rich C-H functionalisation reactions. The workflow was benchmarked against 35 experimentally determined C-H hydricities in DMSO, yielding a mean absolute error (MAE) of 4.43 kcal/mol and a root mean squared error (RMSE) of 5.45 kcal/mol. Leveraging this approach, we generated a dataset of 3278 C-H sites across 740 molecules to train a machine learning (ML) model based on CM5 atomic charge descriptors, achieving an MAE of 2.30 kcal/mol and an RMSE of 3.74 kcal/mol relative to QM-computed hydricities. The method was further applied to 250 hydride transfer-like reactions, including C-N, C-C, and C-X bond formations, carbene insertions, and oxidative transformations. Comparative analysis with ALFABET, a bond dissociation energy (BDE)-based ML model, reveals that hydricity predictions, when combined with steric accessibility, correctly identify the reactive site in eight out of ten representative reactions, surpassing BDEs in most cases. These findings highlight hydricity as a complementary and, in some cases, superior descriptor for guiding regioselectivity predictions in electron-rich C-H functionalisation. The model is made available at regioselect.org, together with a host of other reactivity predictors.","PeriodicalId":8756,"journal":{"name":"Beilstein Journal of Organic Chemistry","volume":"22 ","pages":"603-610"},"PeriodicalIF":2.7,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13159236/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147925870","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}

引用次数: 0

Design and synthesis of an erdafitinib-based selective FGFR2 degrader. 基于厄达非替尼的选择性FGFR2降解剂的设计与合成。

IF 2.7 4区化学

Beilstein Journal of Organic Chemistry Pub Date : 2026-04-15 eCollection Date: 2026-01-01 DOI: 10.3762/bjoc.22.44

Yumeng Jin, Shidong Wang, Sihan Pan, Shuqi Huang, Weichen Zhou, Xiaohao Huang, Lei Zheng, Lingfeng Chen

{"title":"Design and synthesis of an erdafitinib-based selective FGFR2 degrader.","authors":"Yumeng Jin, Shidong Wang, Sihan Pan, Shuqi Huang, Weichen Zhou, Xiaohao Huang, Lei Zheng, Lingfeng Chen","doi":"10.3762/bjoc.22.44","DOIUrl":"10.3762/bjoc.22.44","url":null,"abstract":"This study aimed to develop a novel degrader capable of selectively degrading fibroblast growth factor receptor 2 (FGFR2) to overcome the issues of drug resistance and adverse reactions associated with traditional inhibitors in the treatment of FGFR2-driven tumors. Erdafitinib was employed as the targeting ligand, and its aliphatic amine site was conjugated with a CRBN E3 ligase ligand to design and synthesize a series of PROTAC molecules with different linkers. Screening was performed in KATO III cells with high FGFR2 expression, leading to the identification of LC-JD-6 as a potent degrader. Experimental results demonstrated that LC-JD-6 effectively induced FGFR2 protein degradation with a half-maximal degrading concentration (DC50) of 121.4 nM, and this effect exhibited time- and concentration-dependence. Assessed at the cellular level, LC-JD-6 has a half-maximal inhibitory concentration in the KATO III (IC50) of 96.0 nM and showed low inhibitory activity in normal cells. Selectivity analysis revealed that LC-JD-6 specifically degraded FGFR2 with minimal impact on other FGFR subtypes. Further studies confirmed that LC-JD-6 also efficiently reduced the expression of FGFR2 on the cell membrane surface. In conclusion, this study successfully developed LC-JD-6, a novel FGFR2-selective degrader, and for the first time confirmed its ability to degrade the membrane-bound form of FGFR2. This work provides an innovative targeted protein degradation strategy for the treatment of FGFR2-driven tumors and holds significant potential for clinical application.","PeriodicalId":8756,"journal":{"name":"Beilstein Journal of Organic Chemistry","volume":"22 ","pages":"583-591"},"PeriodicalIF":2.7,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13159326/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147925856","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}

引用次数: 0

Continuous-flow carbonyl hydrogenation under subatmospheric to atmospheric hydrogen pressure enabled by robust heterogeneous Pt-Fe catalysts. 坚固的非均相Pt-Fe催化剂实现了亚常压到常压下连续流动羰基加氢。

IF 2.7 4区化学

Beilstein Journal of Organic Chemistry Pub Date : 2026-04-10 eCollection Date: 2026-01-01 DOI: 10.3762/bjoc.22.43

Hiroyuki Miyamura, Ryosuke Kajiyama, Shun-Ya Onozawa, Yoshihiro Kon, Shū Kobayashi

引用次数: 0

Kinetic resolution of racemic planar-chiral vinylcymantrenes by molybdenum-catalyzed asymmetric metathesis dimerization. 钼催化不对称复合二聚化对外消旋平面手性乙烯基氰烯的动力学拆分。

IF 2.7 4区化学

Beilstein Journal of Organic Chemistry Pub Date : 2026-03-31 eCollection Date: 2026-01-01 DOI: 10.3762/bjoc.22.42

Haruna Imazu, Hitoshi Izu, Yasuhiro Ohki, Masamichi Ogasawara

引用次数: 0

Molecular tweezer-peptide conjugates disrupt the protein-protein interaction between survivin and histone H3 essential in mitosis. 分子镊子-肽偶联物破坏有丝分裂中必需的survivin和组蛋白H3之间的蛋白质相互作用。

IF 2.7 4区化学

Beilstein Journal of Organic Chemistry Pub Date : 2026-03-27 eCollection Date: 2026-01-01 DOI: 10.3762/bjoc.22.41

Catherine Gsell, Philipp Rebmann, Karina Opara, Christine Beuck, Peter Bayer, David Bier, Ingrid R Vetter, Thomas Schrader

{"title":"Molecular tweezer-peptide conjugates disrupt the protein-protein interaction between survivin and histone H3 essential in mitosis.","authors":"Catherine Gsell, Philipp Rebmann, Karina Opara, Christine Beuck, Peter Bayer, David Bier, Ingrid R Vetter, Thomas Schrader","doi":"10.3762/bjoc.22.41","DOIUrl":"10.3762/bjoc.22.41","url":null,"abstract":"Peptide-modified supramolecular tweezers, a promising new class of chemical tools, were designed and employed to inhibit the interaction of the BIR domain of human survivin, a member of the chromosomal passenger complex (CPC), with the phosphorylated histone H3 N-terminal peptide. Fluorescence polarization measurements revealed a nanomolar affinity of the BIR domain for the peptide-tweezer, depending on the presence of lysine residue 121, as proven by the K121A mutant of survivin. Two crystal structures of C-terminally truncated human survivin with the peptide-tweezer molecules demonstrated that the peptide moiety binds the BIR domain as expected from the well-known published crystal structures of survivin with various peptides, but the tweezer itself, surprisingly, was bound to a putative Ca2+ ion and the side chain of Pro26, corresponding to a previously unknown binding mode. Guided by the accessibility of survivin's lysine residues in the CPC, a number of new promising peptide tweezers was synthesized, able to connect both binding sites on the protein.","PeriodicalId":8756,"journal":{"name":"Beilstein Journal of Organic Chemistry","volume":"22 ","pages":"557-567"},"PeriodicalIF":2.7,"publicationDate":"2026-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13040270/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147608090","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}

引用次数: 0

Experimental and DFT studies on the regioselective methanolysis of 5-azido-9-oxabicyclo[6.1.0]nonan-4-yl 4-nitrobenzoate isomers. 5-叠氮-9-恶沙环[6.1.0]壬胺-4-酰基4-硝基苯甲酸异构体区域选择性甲醇分解的实验和DFT研究。

IF 2.7 4区化学

Beilstein Journal of Organic Chemistry Pub Date : 2026-03-26 eCollection Date: 2026-01-01 DOI: 10.3762/bjoc.22.40

İlknur Polat, Selçuk Eşsiz, Emine Salamci

引用次数: 0

Melifoliox B, a novel phloroglucin derivative isolated from Melicope barbigera (Rutaceae) and synthesis of new oxidation products from melifoliones A and B. 从芸香科百合花中分离得到一种新的间苯绿素衍生物Melifoliox B，并合成了新的氧化产物。

IF 2.7 4区化学

Beilstein Journal of Organic Chemistry Pub Date : 2026-03-24 eCollection Date: 2026-01-01 DOI: 10.3762/bjoc.22.39

Horst Weber, Kim-Thao Tran-Cong, Bernhard Mayer, Guido J Reiss, Iryna S Konovalova, Marc S Appelhans, Kenneth R Wood, Claus M Passreiter

{"title":"Melifoliox B, a novel phloroglucin derivative isolated from Melicope barbigera (Rutaceae) and synthesis of new oxidation products from melifoliones A and B.","authors":"Horst Weber, Kim-Thao Tran-Cong, Bernhard Mayer, Guido J Reiss, Iryna S Konovalova, Marc S Appelhans, Kenneth R Wood, Claus M Passreiter","doi":"10.3762/bjoc.22.39","DOIUrl":"10.3762/bjoc.22.39","url":null,"abstract":"In addition to new acetophenones and 2H-chromenes, the dichlormethane extract from leaves of Melicope barbigera A. Gray (Rutaceae) afforded a mixture of the isomeric melifoliones A (1) and B (2) as well as an oxidation product of 2, whose structure was elucidated as the para-quinol 4. For an independent synthesis of 4 and its possible isomer 3, the required compounds 1 and 2 were synthesized as a mixture of the isomers starting from chromene 5, briefly heated in a closed microwave apparatus with catalytic amounts of acetic acid. Forced heating of 5 in acetic acid or use of stronger acids lead to the benzoxocin derivatives 6 and 7. Oxidation of melifoliones 1 and 2 under a great variety of oxidants and conditions failed to give 3 and 4. Iodine-containing oxidants yielded the products 8, 9, and 10. Combined oxidation with hydrogen peroxide and ferricyanide in alkaline solution resulted in an unexpected contraction of the acetyl phenol to a furanone ring, forming the derivatives 11 and 12, whose structures were confirmed by X-ray analysis. A hypothetical mechanism for the oxidative ring contraction is proposed. 11 and 12 are the first representatives of new heterocyclic ring systems that have not previously been described in the literature.","PeriodicalId":8756,"journal":{"name":"Beilstein Journal of Organic Chemistry","volume":"22 ","pages":"535-546"},"PeriodicalIF":2.7,"publicationDate":"2026-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13040265/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147608102","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}

引用次数: 0