ChemistryEurope最新文献_第3页

Acetylation-Deacetylation-Driven Natural Product Biosynthesis 乙酰化-去乙酰化驱动的天然产物生物合成

ChemistryEurope Pub Date : 2025-04-28 DOI: 10.1002/ceur.202500025

Huibin Wang, Ikuro Abe

{"title":"Acetylation-Deacetylation-Driven Natural Product Biosynthesis","authors":"Huibin Wang, Ikuro Abe","doi":"10.1002/ceur.202500025","DOIUrl":"https://doi.org/10.1002/ceur.202500025","url":null,"abstract":"Acetylation introduces acetyl groups to substrates, thus altering their chemical reactivity and stability, and plays a crucial role in natural product biosynthesis by driving structural diversification and functional optimization. Emerging evidence now highlights cryptic acetylations as transient modifications that guide sequential reactions, enabling the efficient assembly of bioactive molecules. Here, we systematically examine the multifaceted roles of acetylation-deacetylation dynamics in natural product biosynthesis, with particular emphasis on four key mechanistic paradigms. First, we explore the strategy of acetylation followed by deacetylation after several biosynthetic steps, which serves as a protective and directing mechanism. Second, we investigate acetylation-mediated rearrangement, where the introduction of an acetyl group triggers structural rearrangement to generate novel molecular architectures. Third, we analyze acetylation-triggered elimination, a process that facilitates the formation of crucial double bonds in molecular scaffolds. Finally, we discuss the acetylation cycle as a regulatory mechanism, highlighting its role in controlling biosynthetic flux and intermediate stability. We also examine the challenges of identifying and characterizing cryptic acetylations, while highlighting future opportunities to harness these modifications for synthetic biology. By elucidating the hidden roles of acetylation-deacetylation dynamics, this not only deepens our understanding of natural product biosynthesis but also provides innovative strategies for future drug discovery.","PeriodicalId":100234,"journal":{"name":"ChemistryEurope","volume":"3 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ceur.202500025","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144634983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Reduction of CO2 and Related Compounds with a Low-Valent CaI Synthon 用低价CaI合成物还原CO2及相关化合物

ChemistryEurope Pub Date : 2025-04-27 DOI: 10.1002/ceur.202500080

Stefan Thum, Jonathan Mai, Neha Patel, Jens Langer, Sjoerd Harder

{"title":"Reduction of CO2 and Related Compounds with a Low-Valent CaI Synthon","authors":"Stefan Thum, Jonathan Mai, Neha Patel, Jens Langer, Sjoerd Harder","doi":"10.1002/ceur.202500080","DOIUrl":"https://doi.org/10.1002/ceur.202500080","url":null,"abstract":"The reduction of CO2 with low-valent s-block metal complexes is limited to MgI reducing agents. Herein, the reduction of a series of CX2 reagents (X = O, S, NiPr) with the CaI synthon [(BDI)Ca(THP)]2(N2) (VI) is described, which is a CaII complex that reacts like the hypothetical CaI complex (BDI)CaCa(BDI); BDI = HC[(Me)-N(DIPeP)]2, DIPeP = 2,6-Et2CH-phenyl, THP = tetrahydropyran. Reaction of VI with excess CO2 led to crystallization of a carbonate complex with a Ca4(CO3)24+ core. The stabilizing BDI ligands also react by nucleophilic addition of CO2 at the backbone γ-C atom. Reaction with only two equivalents of CO2 gave the presumed carbonite (CO22−) intermediate, but this could not be confirmed by X-ray diffraction. Reaction with CS2 gave the first unique s-block metal complex with a CS22− anion. This anion bridges between two (BDI)Ca+ cations by CaC and CaS bonding. The reduction of iPrN=C=NiPr with VI gave C–C coupling to a [(iPrN)2C–C(NiPr)2]2− dianion. An intermediate with a C(NiPr)22− dianion could not be isolated.","PeriodicalId":100234,"journal":{"name":"ChemistryEurope","volume":"3 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ceur.202500080","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144635646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mono-Ethyl-Phosphonates: Functional Group Masking Strategy to Stabilize and Optimize the Pharmacokinetics of Rare Earth Radiochelates 单膦酸乙酯：稳定和优化稀土放射性螯合物药代动力学的官能团掩蔽策略

ChemistryEurope Pub Date : 2025-04-26 DOI: 10.1002/ceur.202500079

Jennifer N. Whetter, Axia Marlin, Edith K. Amason, Eduardo Aluicio-Sarduy, Angus J. Koller, Phuong Nguyen Tran, Kaelyn V. Becker, Jonathan W. Engle, Eszter Boros

{"title":"Mono-Ethyl-Phosphonates: Functional Group Masking Strategy to Stabilize and Optimize the Pharmacokinetics of Rare Earth Radiochelates","authors":"Jennifer N. Whetter, Axia Marlin, Edith K. Amason, Eduardo Aluicio-Sarduy, Angus J. Koller, Phuong Nguyen Tran, Kaelyn V. Becker, Jonathan W. Engle, Eszter Boros","doi":"10.1002/ceur.202500079","DOIUrl":"https://doi.org/10.1002/ceur.202500079","url":null,"abstract":"Prodrug strategies are widely used to enhance the pharmacokinetics of organic, small molecule drugs. Herein, this approach to rare earth coordination complexes is adopted with potential applications as diagnostic and therapeutic radiopharmaceuticals. Previously, the chelator m-phospatcn (H4L2) is identified as suitable for radiolabeling with 44Sc and 177Lu at room temperature. However, functionalizing H4L2 for targeting vector conjugation destabilizes the 44Sc chelates, leading to increased blood retention, liver accumulation, and bone deposition. To address this, an ethyl group to mask one phosphonate oxygen (H3L2-Et) is introduced. Spectrophotometric studies reveal reduced thermodynamic stability for [Sc(L2-Et)] and [Lu(L2-Et)] when compared with their phosphonate parent complexes. Radiolabeling with 44Sc and 177Lu remains efficient at ≤ 40 °C (155-906 mCi μmol−1) with corresponding radiochelates remaining >87% and >98% inert in plasma after one isotope half-life. In vivo biodistribution experiments indicate reduced blood retention and bone uptake for the lead model-bifunctional [44Sc][Sc(L2-Et-Aga)]. prostate specific membrane antigen (PSMA)-targeted derivative, L2-Et-aga-DUPA, affords 44Sc and 177Lu radiochemical complexes at ≤40 °C and selectively localizes in PSMA-expressing tumors with minimal off-target uptake.","PeriodicalId":100234,"journal":{"name":"ChemistryEurope","volume":"3 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ceur.202500079","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144635638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Evolution of a Strategy for the Total Synthesis of the Ganoderma Meroterpenoid Ganoapplanin 灵芝萜类灵芝素全合成策略的进化

ChemistryEurope Pub Date : 2025-04-26 DOI: 10.1002/ceur.202500020

Nicolas Müller, Ondřej Kováč, Alexander Rode, Daniel Atzl, Clemens Dietrich, Ana V. Serna, Sebastian Schaar, Antonio Paparesta, Julian Lichtenegger, Thomas Magauer

{"title":"Evolution of a Strategy for the Total Synthesis of the Ganoderma Meroterpenoid Ganoapplanin","authors":"Nicolas Müller, Ondřej Kováč, Alexander Rode, Daniel Atzl, Clemens Dietrich, Ana V. Serna, Sebastian Schaar, Antonio Paparesta, Julian Lichtenegger, Thomas Magauer","doi":"10.1002/ceur.202500020","DOIUrl":"https://doi.org/10.1002/ceur.202500020","url":null,"abstract":"Herein, a detailed account of the efforts leading to the recently published synthesis of the Ganoderma meroterpenoid ganoapplanin, a natural product identified as an inhibitor of T-type voltage-gated calcium channels, is provided. Ganoapplanin, which was isolated as a racemate from the fungus Ganoderma applanatum in 2016, features a complex structure, including a characteristic spiro bisacetal structure, a highly functionalized tetra-ortho-substituted biaryl motif, and a propellane-like dioxatricyclo[4.3.3.0]dodecane scaffold. While the southern terpenoid fragment is available via a diastereoselective titanium-mediated iodolactonization, considerable efforts are required to fuse this fragment with various aromatic fragments. The breakthrough was achieved by a highly efficient two-component coupling strategy that simultaneously fuses the fragments and establishes the crucial biaryl bond. This transformation involves an intramolecular 6-exo-trig radical addition of a quinone monoacetal, followed by an intermolecular aldol addition. Finally, strategic late-stage oxidations enabled the formation of the characteristic spiro bisacetal motif and the completion of the synthesis of ganoapplanin.","PeriodicalId":100234,"journal":{"name":"ChemistryEurope","volume":"3 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ceur.202500020","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143950222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Introduction of a Phosphine Group onto the Ferrocene Moiety in Ferrociphenol Opens Access to New Heterobimetallic Complexes with Anticancer Activity 在铁酚的二茂铁基团上引入膦基团开辟了新的具有抗癌活性的杂双金属配合物的途径

ChemistryEurope Pub Date : 2025-04-24 DOI: 10.1002/ceur.202500048

Magda Křelinová, Michèle Salmain, Petr Štěpnička, Ivana Císařová, Benoît Bertrand, Jiří Schulz

{"title":"Introduction of a Phosphine Group onto the Ferrocene Moiety in Ferrociphenol Opens Access to New Heterobimetallic Complexes with Anticancer Activity","authors":"Magda Křelinová, Michèle Salmain, Petr Štěpnička, Ivana Císařová, Benoît Bertrand, Jiří Schulz","doi":"10.1002/ceur.202500048","DOIUrl":"https://doi.org/10.1002/ceur.202500048","url":null,"abstract":"Ferrocene analogs of biologically active compounds often exert favorable properties, as demonstrated by ferrocifens derived from the selective estrogen receptor modulator tamoxifen. This contribution reports an original approach to modify the structure of one of the first ferrocifens, namely ferrociphenol, by means of a diphenylphosphinyl moiety appended to the unsubstituted cyclopentadienyl ring of the ferrocene unit. The phosphine-substituted ferrociphenol 1 is synthesized by two alternative routes and fully characterized including structure determination. Compound 1 is converted to the corresponding phosphonium salt 1·MeI and used to prepare a series of bimetallic (arene)metal and chloridogold(I) complexes. The biological evaluation reveals a relatively lower antiproliferative activity of the newly synthesized compounds compared to the parent ferrociphenol and [AuCl(FcPPh2-κP)] (Fc = ferrocenyl) toward both tumorigenic and nontumorigenic cells. All the compounds exhibit complicated redox behavior due to chemical steps that follow the initial, ferrocene-centered oxidation. Overall, the collected data indicate that the introduced phosphine substituent affects the redox and biological properties of the resulting compounds and, very likely, their mode of action.","PeriodicalId":100234,"journal":{"name":"ChemistryEurope","volume":"3 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ceur.202500048","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144635620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Clean 1H NMR Spectra of Products Directly from Batch and Flow Reaction Mixtures 清洁的1H核磁共振光谱直接从批和流动反应混合物的产品

ChemistryEurope Pub Date : 2025-04-24 DOI: 10.1002/ceur.202500038

Yuliia Horbenko, Martin Jaudronnet, Nour El Sabbagh, Margherita Bazzoni, Aurélie Bernard, Mathias Nilsson, Patrick Giraudeau, François-Xavier Felpin, Jean-Nicolas Dumez

{"title":"Clean 1H NMR Spectra of Products Directly from Batch and Flow Reaction Mixtures","authors":"Yuliia Horbenko, Martin Jaudronnet, Nour El Sabbagh, Margherita Bazzoni, Aurélie Bernard, Mathias Nilsson, Patrick Giraudeau, François-Xavier Felpin, Jean-Nicolas Dumez","doi":"10.1002/ceur.202500038","DOIUrl":"https://doi.org/10.1002/ceur.202500038","url":null,"abstract":"Nuclear magnetic resonance (NMR) spectroscopy is widely used for the monitoring of chemical reactions. Flow NMR methods are being increasingly used to monitor reactions carried out in either batch or flow synthesis mode. Kinetic information is commonly obtained by integration of assigned peaks across a series of spectra. However, the complexity of NMR spectra in reaction mixtures can result in peak overlap and assignment issues, which make it difficult to recover the clean complete spectrum of compounds involved in the reaction. Multiway analysis methods can in principle be used to separate information on compounds in a mixture, but they are demanding on the quality and form of the input data. Herein, it is shown how the multiway analysis of time-resolved diffusion NMR data can yield the clean spectrum of newly formed compounds, for a selection of click reactions carried out in batch and in flow, when monitored by flow NMR. The use of a fast and robust diffusion NMR approach, together with careful processing, yields high-quality data, even for continuously flowing samples, which was previously inaccessible. Multiway analysis then yields 1D 1H spectra together with concentration changes. The proposed approach is expected to be particularly useful for reaction monitoring applications.","PeriodicalId":100234,"journal":{"name":"ChemistryEurope","volume":"3 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ceur.202500038","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143950525","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","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 Organic Electrosynthesis: The Role of Overcharge Protectors 计算有机电合成：过充保护器的作用

ChemistryEurope Pub Date : 2025-04-22 DOI: 10.1002/ceur.202500032

Marina Díaz-Ruiz, Feliu Maseras

{"title":"Computational Organic Electrosynthesis: The Role of Overcharge Protectors","authors":"Marina Díaz-Ruiz, Feliu Maseras","doi":"10.1002/ceur.202500032","DOIUrl":"https://doi.org/10.1002/ceur.202500032","url":null,"abstract":"Organic electrosynthesis is a powerful technique that provides enhanced yields along with key advantages such as atom economy, sustainability, and improved selectivity. However, its comprehensive mechanistic understanding remains challenging due to its complex and often non-trivial nature. Herein, a complete computational investigation of a nickel-catalyzed electrochemical cross electrophile coupling reaction is reported, previously reported by Sevov and coworkers, which is facilitated by an overcharge protector. Our approach combines density functional theory calculations with microkinetic modeling to first elucidate the reaction mechanism in solution and then to characterize the electrodic processes, where the catalyst degradation competes with protector reduction. To account for this competition, the electric current is incorporated into the microkinetic simulations by defining the electron transfer rate. All components are integrated into the model, simulating the reaction both with and without the protector, achieving good reproduction of the experimental results and leading to a better understanding of its mechanistic features.","PeriodicalId":100234,"journal":{"name":"ChemistryEurope","volume":"3 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ceur.202500032","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143950234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Blueprints for the Geometric Control of N-Heterocyclic Carbene–Carbodiimide Isomers n -杂环碳-碳二亚胺异构体的几何控制蓝图

ChemistryEurope Pub Date : 2025-04-20 DOI: 10.1002/ceur.202500023

Craig S. Day, Niklas Grabicki, Daniel B. K. Chu, Allison Keys, Avni Singhal, Vyshnavi Vennelakanti, Ilia Kevlishvili, Rafael Gómez-Bombarelli, Heather J. Kulik, Jeremiah Johnson

引用次数: 0

Ball-Milling-Promoted Copper-Catalyzed Solid-State Radical C–H Difluoroalkylation Reactions 球磨促进铜催化固态自由基C-H二氟烷基化反应

ChemistryEurope Pub Date : 2025-04-17 DOI: 10.1002/ceur.202500046

Ran Zhang, Chen-Zhe Yun, Hong Lu, Hao Wei

引用次数: 0

Tryptophan-Selective Chemical Modification of Peptides by Thioether-Mediated Sulfenylation 硫醚介导的磺化对多肽的色氨酸选择性化学修饰

ChemistryEurope Pub Date : 2025-04-13 DOI: 10.1002/ceur.202500059

Hayate Shida, Akihiro Taguchi, Yuma Tokita, Yan Cui, Momoka Sakamaki, Sho Konno, Atsuhiko Taniguchi, Young Sook Yun, Yuuta Fujikawa, Hiroshi Kaneko, Hidemasa Nakaminami, Yoshio Hayashi

{"title":"Tryptophan-Selective Chemical Modification of Peptides by Thioether-Mediated Sulfenylation","authors":"Hayate Shida, Akihiro Taguchi, Yuma Tokita, Yan Cui, Momoka Sakamaki, Sho Konno, Atsuhiko Taniguchi, Young Sook Yun, Yuuta Fujikawa, Hiroshi Kaneko, Hidemasa Nakaminami, Yoshio Hayashi","doi":"10.1002/ceur.202500059","DOIUrl":"https://doi.org/10.1002/ceur.202500059","url":null,"abstract":"Chemical modification of biomolecules such as peptides and proteins is an important technology for the development of new functional molecules. Herein, a thioether-mediated sulfenylation for tryptophan (Trp)-selective chemical modification under mild metal-free reaction conditions involving a weak acid/water solvent is reported. An electrophilic species generated from 4-fluorophenyl 3-nitro-2-pyridinesulfenate, Npys-OPh(pF), in the presence of a thioether component, enables efficient sulfenylation of the Trp residue on various Trp-containing biologically active linear and cyclic peptides. In addition, this sulfenylation to late-stage chemical modification of a natural cyclic depsipeptide, daptomycin, is expanded and Trp-sulfenylated derivatives, including fluorescent-labeled derivatives, are obtained. The results indicate that the thioether-mediated sulfenylation can be used as a robust Trp-selective chemical modification method for peptides in a wide range of applications.","PeriodicalId":100234,"journal":{"name":"ChemistryEurope","volume":"3 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ceur.202500059","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143950140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0