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High-Resolution Substrate Specificity Profiling of SARS-CoV-2 Mpro; Comparison to SARS-CoV Mpro. SARS-CoV-2 Mpro 的高分辨率底物特异性分析;与 SARS-CoV Mpro 的比较。
IF 3.5 2区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-07-19 Epub Date: 2024-06-12 DOI: 10.1021/acschembio.4c00096
Rasha M Yaghi, Collin L Andrews, Dennis C Wylie, Brent L Iverson

The SARS-CoV-2 Mpro protease from COVID-19 cleaves the pp1a and pp2b polyproteins at 11 sites during viral maturation and is the target of Nirmatrelvir, one of the two components of the frontline treatment sold as Paxlovid. We used the YESS 2.0 platform, combining protease and substrate expression in the yeast endoplasmic reticulum with fluorescence-activated cell sorting and next-generation sequencing, to carry out the high-resolution substrate specificity profiling of SARS-CoV-2 Mpro as well as the related SARS-CoV Mpro from SARS 2003. Even at such a high level of resolution, the substrate specificity profiles of both enzymes are essentially identical. The population of cleaved substrates isolated in our sorts is so deep, the relative catalytic efficiencies of the different cleavage sites on the SARS-CoV-2 polyproteins pp1a and pp2b are qualitatively predicted. These results not only demonstrated the precise and reproducible nature of the YESS 2.0/NGS approach to protease substrate specificity profiling but also should be useful in the design of next generation SARS-CoV-2 Mpro inhibitors, and by analogy, SARS-CoV Mpro inhibitors as well.

来自 COVID-19 的 SARS-CoV-2 Mpro 蛋白酶在病毒成熟过程中会在 11 个位点上裂解 pp1a 和 pp2b 多聚蛋白,它是 Nirmatrelvir 的靶标,而 Nirmatrelvir 是以 Paxlovid 出售的一线治疗药物的两种成分之一。我们使用 YESS 2.0 平台,将酵母内质网中蛋白酶和底物的表达与荧光激活细胞分选和下一代测序结合起来,对 SARS-CoV-2 Mpro 以及 SARS 2003 中的相关 SARS-CoV Mpro 进行了高分辨率底物特异性分析。即使在如此高的分辨率下,两种酶的底物特异性图谱也基本相同。在我们的研究中分离出的裂解底物群非常深,可以定性地预测 SARS-CoV-2 多聚蛋白 pp1a 和 pp2b 上不同裂解位点的相对催化效率。这些结果不仅证明了 YESS 2.0/NGS 蛋白酶底物特异性分析方法的精确性和可重复性,而且对设计下一代 SARS-CoV-2 Mpro 抑制剂以及类推设计 SARS-CoV Mpro 抑制剂非常有用。
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引用次数: 0
Limiting the Broadcast Range of a Secreting Cell during Intercellular Signaling Using Protease-Mediated Degradation. 利用蛋白酶介导的降解限制分泌细胞在细胞间信号传递过程中的广播范围
IF 3.7 2区 生物学 Q1 BIOCHEMICAL RESEARCH METHODS Pub Date : 2024-07-19 Epub Date: 2024-06-17 DOI: 10.1021/acssynbio.4c00042
Joshua Cole, Rebecca Schulman

Synthetic biology is revolutionizing our approaches to biocomputing, diagnostics, and environmental monitoring through the use of designed genetic circuits that perform a function within a single cell. More complex functions can be performed by multiple cells that coordinate as they perform different subtasks. Cell-cell communication using molecular signals is particularly suited for aiding in this communication, but the number of molecules that can be used in different communication channels is limited. Here we investigate how proteases can limit the broadcast range of communicating cells. We find that adding barrierpepsin to Saccharomyces cerevisiae cells in two-dimensional multicellular networks that use α-factor signaling prevents cells beyond a specific radius from responding to α-factor signals. Such limiting of the broadcast range of cells could allow multiple cells to use the same signaling molecules to direct different communication processes and functions, provided that they are far enough from one another. These results suggest a means by which complex synthetic cellular networks using only a few signals for communication could be created by structuring a community of cells to create distinct broadcast environments.

合成生物学正在彻底改变我们的生物计算、诊断和环境监测方法,其方法是利用设计好的基因电路在单个细胞内实现某种功能。更复杂的功能可由多个细胞执行,它们在执行不同的子任务时相互协调。利用分子信号进行的细胞间通信尤其适用于辅助这种通信,但可用于不同通信渠道的分子数量有限。在这里,我们研究了蛋白酶如何限制通信细胞的广播范围。我们发现,在使用α-因子信号的二维多细胞网络中,向酿酒酵母细胞中添加屏障胃蛋白酶,可阻止特定半径以外的细胞对α-因子信号做出反应。这种对细胞广播范围的限制可以让多个细胞使用相同的信号分子来引导不同的通信过程和功能,前提是它们之间的距离足够远。这些结果表明,通过构建细胞群落以创造不同的广播环境,可以创建只使用少量信号进行通信的复杂合成细胞网络。
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引用次数: 0
Sustainable Synthesis of Novel Green-Based Nanoparticles for Therapeutic Interventions and Environmental Remediation. 用于治疗干预和环境修复的新型绿色纳米粒子的可持续合成。
IF 3.7 2区 生物学 Q1 BIOCHEMICAL RESEARCH METHODS Pub Date : 2024-07-19 Epub Date: 2024-06-20 DOI: 10.1021/acssynbio.4c00206
Swati Singh, Harshita Tiwari, Ashish Verma, Priyamvada Gupta, Amrit Chattopadhaya, Ananya Singh, Sanjana Singh, Brijesh Kumar, Abhijit Mandal, Rajiv Kumar, Ashok K Yadav, Hemant Kumar Gautam, Vibhav Gautam

The advancement in nanotechnology has completely revolutionized various fields, including pharmaceutical sciences, and streamlined the potential therapeutic of many diseases that endanger human life. The synthesis of green nanoparticles by biological processes is an aspect of the newly emerging scientific field known as "green nanotechnology". Due to their safe, eco-friendly, nontoxic nature, green synthesis tools are better suited to produce nanoparticles between 1 and 100 nm. Nanoformulation of different types of nanoparticles has been made possible by using green production techniques and commercially feasible novel precursors, such as seed extracts, algae, and fungi, that act as potent reducing, capping, and stabilizing agents. In addition to this, the biofunctionalization of nanoparticles has also broadened its horizon in the field of environmental remediation and various novel therapeutic innovations including wound healing, antimicrobial, anticancer, and nano biosensing. However, the major challenge pertaining to green nanotechnology is the agglomeration of nanoparticles that may alter the surface topology, which can affect biological physiology, thereby contributing to system toxicity. Therefore, a thorough grasp of nanoparticle toxicity and biocompatibility is required to harness the applications of nanotechnology in therapeutics.

纳米技术的进步彻底改变了包括制药科学在内的各个领域,并简化了许多危及人类生命的疾病的潜在治疗方法。通过生物过程合成绿色纳米粒子是新兴科学领域 "绿色纳米技术 "的一个方面。由于绿色合成工具安全、环保、无毒,因此更适合生产 1 至 100 纳米的纳米粒子。通过使用绿色生产技术和商业上可行的新型前体(如种子提取物、藻类和真菌),不同类型纳米粒子的纳米制备成为可能,这些前体可作为有效的还原剂、封盖剂和稳定剂。除此之外,纳米粒子的生物功能化还拓宽了其在环境修复和各种新型治疗创新领域的应用范围,包括伤口愈合、抗菌、抗癌和纳米生物传感。然而,绿色纳米技术面临的主要挑战是纳米粒子的聚集可能会改变表面拓扑结构,从而影响生物生理机能,造成系统毒性。因此,需要全面掌握纳米粒子的毒性和生物相容性,以利用纳米技术在治疗方面的应用。
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引用次数: 0
Optical Control of TRPV1 Channels In Vitro with Tethered Photopharmacology. 利用系留光药理学对体外 TRPV1 通道进行光学控制。
IF 3.5 2区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-07-19 Epub Date: 2024-06-21 DOI: 10.1021/acschembio.4c00052
Carmel L Howe, David Icka-Araki, Alexander E G Viray, Sarahi Garza, James A Frank

Transient receptor potential vanilloid 1 (TRPV1) is a nonselective cation channel that is important for nociception and inflammatory pain and is activated by a variety of nociceptive stimuli─including lipids such as capsaicin (CAP) and endocannabinoids. TRPV1's role in physiological systems is often studied by activating it with externally perfused ligands; however, this approach is plagued by poor spatiotemporal resolution. Lipid agonists are insoluble in physiological buffers and can permeate membranes to accumulate nonselectively inside cells, where they can have off-target effects. To increase the spatiotemporal precision with which we can activate lipids on cells and tissues, we previously developed optically cleavable targeted (OCT) ligands, which use protein tags (SNAP-tags) to localize a photocaged ligand on a target cellular membrane. After enrichment, the active ligand is released on a flash of light to activate nearby receptors. In our previous work, we developed an OCT-ligand to control a cannabinoid-sensitive GPCR. Here, we expand the scope of OCT-ligand technology to target TRPV1 ion channels. We synthesize a probe, OCT-CAP, that tethers to membrane-bound SNAP-tags and releases a TRPV1 agonist when triggered by UV-A irradiation. Using Ca2+ imaging and electrophysiology in HEK293T cells expressing TRPV1, we demonstrate that OCT-CAP uncaging activates TRPV1 with superior spatiotemporal precision when compared to standard diffusible ligands or photocages. This study is the first example of an OCT-ligand designed to manipulate an ion-channel target. We anticipate that these tools will find many applications in controlling lipid signaling pathways in various cells and tissues.

瞬时受体电位类香草素 1(TRPV1)是一种非选择性阳离子通道,对痛觉和炎症性疼痛非常重要,可被多种痛觉刺激物激活--包括脂质,如辣椒素(CAP)和内源性大麻素。研究 TRPV1 在生理系统中的作用时,通常使用外部灌注的配体激活 TRPV1;然而,这种方法存在时空分辨率低的问题。脂质激动剂不溶于生理缓冲液,可穿透细胞膜在细胞内非选择性聚集,产生脱靶效应。为了提高激活细胞和组织上脂质的时空精确度,我们之前开发了光学可裂解靶向(OCT)配体,这种配体使用蛋白质标签(SNAP-标签)将光笼配体定位在目标细胞膜上。富集后,活性配体在闪光时释放出来,激活附近的受体。在我们之前的工作中,我们开发了一种 OCT 配体来控制大麻素敏感的 GPCR。在这里,我们将 OCT 配体技术的范围扩大到针对 TRPV1 离子通道。我们合成了一种探针 OCT-CAP,它能与膜结合的 SNAP 标签相连,并在 UV-A 照射触发时释放 TRPV1 激动剂。通过在表达 TRPV1 的 HEK293T 细胞中进行 Ca2+ 成像和电生理学研究,我们证明了与标准扩散配体或光电笼相比,OCT-CAP 能以更高的时空精度激活 TRPV1。这项研究是首个利用 OCT 配体操纵离子通道靶点的实例。我们预计,这些工具将在控制各种细胞和组织的脂质信号通路中得到广泛应用。
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引用次数: 0
Native Aminoacyl-tRNA Synthetase/tRNA Pair Drives Highly Efficient Noncanonical Amino Acid Incorporation in Escherichia coli. 大肠杆菌中的原生氨基酰-tRNA 合成酶/tRNA 对驱动了高效的非规范氨基酸结合。
IF 3.5 2区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-07-19 Epub Date: 2024-06-24 DOI: 10.1021/acschembio.4c00221
Elise D Ficaretta, Soumya Jyoti Singha Roy, Lena Voss, Abhishek Chatterjee

Site-specific noncanonical amino acid (ncAA) mutagenesis in living cells has traditionally relied on heterologous, nonsense-suppressing aminoacyl-tRNA synthetase (aaRS)/tRNA pairs that do not cross-react with their endogenous counterparts. Such heterologous pairs often perform suboptimally in a foreign host cell since they were not evolutionarily optimized to function in the foreign environment. This suboptimal performance restricts the number of ncAAs that can be simultaneously incorporated into a protein. Here, we show that the use of an endogenous aaRS/tRNA pair to drive ncAA incorporation can offer a potential solution to this limitation. To this end, we developed an engineered Escherichia coli strain (ATMY-C321), wherein the endogenous tyrosyl-tRNA synthetase (TyrRS)/tRNA pair has been functionally replaced with an archaeal counterpart, and the release factor 1 has been removed to eliminate competing termination at the UAG nonsense codons. The endogenous TyrRS/tRNACUATyr pair exhibits remarkably efficient nonsense suppression in the resulting cell, relative to established orthogonal ncAA-incorporation systems in E. coli, allowing the incorporation of an ncAA at up to 10 contiguous sites in a reporter protein. Our work highlights the limitations of orthogonal translation systems using heterologous aaRS/tRNA pairs and offers a potential alternative involving the use of endogenous pairs.

活细胞中的位点特异性非典型氨基酸(ncAA)诱变传统上依赖于异源的、抑制无义氨基酸酰-tRNA 合成酶(araRS)/tRNA 对,它们不会与内源对应物发生交叉反应。这种异源配对在外来宿主细胞中的表现往往不尽如人意,因为它们在进化过程中没有经过优化,无法在外来环境中发挥作用。这种次优表现限制了可同时掺入蛋白质的 ncAAs 数量。在这里,我们展示了使用内源性 aaRS/tRNA 对来驱动 ncAA 的整合可以为这一限制提供潜在的解决方案。为此,我们开发了一种工程化大肠杆菌菌株(ATMY-C321),其中的内源性酪氨酰-tRNA合成酶(TyrRS)/tRNA对在功能上被古生物对应物取代,释放因子1被移除,以消除UAG无义密码子处的竞争性终止。内源 TyrRS/tRNACUATyr 对与大肠杆菌中已建立的正交 ncAA-掺入系统相比,在所产生的细胞中表现出非常有效的无义抑制,允许在报告蛋白中多达 10 个连续位点上掺入 ncAA。我们的工作凸显了使用异源 aaRS/tRNA 对的正交翻译系统的局限性,并提供了使用内源对的潜在替代方案。
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引用次数: 0
N-Acyl-N-Alkyl Sulfonamide Probes for Ligand-Directed Covalent Labeling of GPCRs: The Adenosine A2B Receptor as Case Study. 用于配体引导共价标记 GPCR 的 N-酰基-N-烷基磺酰胺探针:腺苷 A2B 受体案例研究。
IF 3.5 2区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-07-19 Epub Date: 2024-06-26 DOI: 10.1021/acschembio.4c00210
Bert L H Beerkens, Vasiliki Andrianopoulou, Xuesong Wang, Rongfang Liu, Gerard J P van Westen, Willem Jespers, Adriaan P IJzerman, Laura H Heitman, Daan van der Es

Small molecular tool compounds play an essential role in the study of G protein-coupled receptors (GPCRs). However, tool compounds most often occupy the orthosteric binding site, hampering the study of GPCRs upon ligand binding. To overcome this problem, ligand-directed labeling techniques have been developed that leave a reporter group covalently bound to the GPCR, while allowing subsequent orthosteric ligands to bind. In this work, we applied such a labeling strategy to the adenosine A2B receptor (A2BAR). We have synthetically implemented the recently reported N-acyl-N-alkyl sulfonamide (NASA) warhead into a previously developed ligand and show that the binding of the A2BAR is not restricted by NASA incorporation. Furthermore, we have investigated ligand-directed labeling of the A2BAR using SDS-PAGE, flow cytometric, and mass spectrometry techniques. We have found one of the synthesized probes to specifically label the A2BAR, although detection was hindered by nonspecific protein labeling most likely due to the intrinsic reactivity of the NASA warhead. Altogether, this work aids the future development of ligand-directed probes for the detection of GPCRs.

小分子工具化合物在研究 G 蛋白偶联受体(GPCR)方面发挥着重要作用。然而,工具化合物通常占据正交结合位点,妨碍了配体结合后 GPCR 的研究。为了克服这一问题,人们开发了配体定向标记技术,这种技术能使报告基团与 GPCR 共价结合,同时允许随后的正交配体结合。在这项研究中,我们将这种标记策略应用于腺苷 A2B 受体(A2BAR)。我们将最近报道的 N-酰基-N-烷基磺酰胺(NASA)弹头合成到之前开发的配体中,结果表明 A2BAR 的结合不受 NASA 结合的限制。此外,我们还使用 SDS-PAGE、流式细胞仪和质谱技术研究了配体对 A2BAR 的定向标记。我们发现合成的探针之一能特异性标记 A2BAR,但检测受到非特异性蛋白质标记的阻碍,这很可能是由于 NASA 弹头的内在反应性造成的。总之,这项工作有助于今后开发用于检测 GPCR 的配体定向探针。
{"title":"<i>N</i>-Acyl-<i>N</i>-Alkyl Sulfonamide Probes for Ligand-Directed Covalent Labeling of GPCRs: The Adenosine A<sub>2B</sub> Receptor as Case Study.","authors":"Bert L H Beerkens, Vasiliki Andrianopoulou, Xuesong Wang, Rongfang Liu, Gerard J P van Westen, Willem Jespers, Adriaan P IJzerman, Laura H Heitman, Daan van der Es","doi":"10.1021/acschembio.4c00210","DOIUrl":"10.1021/acschembio.4c00210","url":null,"abstract":"<p><p>Small molecular tool compounds play an essential role in the study of G protein-coupled receptors (GPCRs). However, tool compounds most often occupy the orthosteric binding site, hampering the study of GPCRs upon ligand binding. To overcome this problem, ligand-directed labeling techniques have been developed that leave a reporter group covalently bound to the GPCR, while allowing subsequent orthosteric ligands to bind. In this work, we applied such a labeling strategy to the adenosine A<sub>2B</sub> receptor (A<sub>2B</sub>AR). We have synthetically implemented the recently reported <i>N</i>-acyl-<i>N</i>-alkyl sulfonamide (NASA) warhead into a previously developed ligand and show that the binding of the A<sub>2B</sub>AR is not restricted by NASA incorporation. Furthermore, we have investigated ligand-directed labeling of the A<sub>2B</sub>AR using SDS-PAGE, flow cytometric, and mass spectrometry techniques. We have found one of the synthesized probes to specifically label the A<sub>2B</sub>AR, although detection was hindered by nonspecific protein labeling most likely due to the intrinsic reactivity of the NASA warhead. Altogether, this work aids the future development of ligand-directed probes for the detection of GPCRs.</p>","PeriodicalId":11,"journal":{"name":"ACS Chemical Biology","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141449019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
HCl/DMSO/HFIP-Mediated Chlorination of Pyrrolo[2,1-a]isoquinolines and Other Electron-Rich Heteroarenes. HCl/DMSO/HFIP 介导的吡咯并[2,1-a]异喹啉和其他富电子杂环戊烯的氯化反应。
IF 3.3 2区 化学 Q1 CHEMISTRY, ORGANIC Pub Date : 2024-07-19 Epub Date: 2024-06-26 DOI: 10.1021/acs.joc.4c00151
Jing Zhou, Xiang Huang, Xin Yu, Liu Yang, Jia-Yi Han, Tsesong Lhazom, Hai-Lei Cui

An efficient oxidative chlorination of pyrrolo[2,1-a]isoquinolines has been established using HCl (aq) as the chlorine source and DMSO as the terminal oxidant in HFIP at ambient temperature. A variety of chlorinated pyrrolo[2,1-a]isoquinoline derivatives have been prepared readily in 23 to 99% yields. This chlorination strategy can be expanded to the functionalization of other electron-rich heteroarenes including substituted pyrroles, indoles, and naphthols.

以盐酸(aq)为氯源,以二甲基亚砜(DMSO)为末端氧化剂,在 HFIP 中于常温下对吡咯并[2,1-a]异喹啉进行高效氧化氯化。各种氯化吡咯并[2,1-a]异喹啉衍生物的制备非常容易,收率在 23% 到 99% 之间。这种氯化策略可以扩展到其他富电子杂环戊烯的官能化,包括取代的吡咯、吲哚和萘酚。
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引用次数: 0
Selective N-functionalization of Arylhydrazines with Primary Alcohols and Acids under PPh3/DDQ System. 在 PPh3/DDQ 系统下芳基肼与伯醇和酸的选择性 N-官能化。
IF 3.3 2区 化学 Q1 CHEMISTRY, ORGANIC Pub Date : 2024-07-19 Epub Date: 2024-06-30 DOI: 10.1021/acs.joc.4c00915
Shubing Shu, Meng Yu, Wenxin Yu, Tao Wang, Zhenming Zhang

We present a PPh3/DDQ-mediated regiospecific selective N-functionalization of arylhydrazines with primary benzylic alcohols and aryl carboxylic acids for the synthesis of N1-benzyl arylhydrazines and N2-acyl arylhydrazines, respectively. This metal- and base-free approach features very short reaction times (about 10 min), broad substrate scope, good functional group tolerance, and mild reaction conditions. Furthermore, N1-benzlated products have also been successfully applied to the concise synthesis of N-substituted indoles and anticancer drug MDM2 inhibitor.

我们介绍了一种 PPh3/DDQ 介导的芳基肼与伯羟基苄醇和芳基羧酸的选择性 N-官能化反应,分别用于合成 N1-苄基芳基肼和 N2-酰基芳基肼。这种不含金属和碱的方法具有反应时间极短(约 10 分钟)、底物范围广、官能团耐受性好以及反应条件温和等特点。此外,N1-苯甲酰化产物还被成功应用于 N-取代吲哚和抗癌药物 MDM2 抑制剂的简易合成。
{"title":"Selective <i>N</i>-functionalization of Arylhydrazines with Primary Alcohols and Acids under PPh<sub>3</sub>/DDQ System.","authors":"Shubing Shu, Meng Yu, Wenxin Yu, Tao Wang, Zhenming Zhang","doi":"10.1021/acs.joc.4c00915","DOIUrl":"10.1021/acs.joc.4c00915","url":null,"abstract":"<p><p>We present a PPh<sub>3</sub>/DDQ-mediated regiospecific selective <i>N</i>-functionalization of arylhydrazines with primary benzylic alcohols and aryl carboxylic acids for the synthesis of <i>N</i><sup>1</sup>-benzyl arylhydrazines and <i>N</i><sup>2</sup>-acyl arylhydrazines, respectively. This metal- and base-free approach features very short reaction times (about 10 min), broad substrate scope, good functional group tolerance, and mild reaction conditions. Furthermore, <i>N</i><sup>1</sup>-benzlated products have also been successfully applied to the concise synthesis of <i>N</i>-substituted indoles and anticancer drug MDM2 inhibitor.</p>","PeriodicalId":57,"journal":{"name":"The Journal of Organic Chemistry","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141464398","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Batch and Continuous-Flow Electrochemical Geminal Difluorination of Indeno[1,2-c]furans. 茚并[1,2-c]呋喃的间歇和连续流电化学双氟化反应。
IF 4.9 1区 化学 Q1 CHEMISTRY, ORGANIC Pub Date : 2024-07-19 Epub Date: 2024-07-05 DOI: 10.1021/acs.orglett.4c02235
Guo-Cai Yuan, Fang-Ling Gao, Kang-Wei Liu, Minggang Li, Yuqi Lin, Ke-Yin Ye

An electrochemical gem-difluorination of indeno[1,2-c]furans using commercially available and easy-to-use triethylamine trihydrofluoride as both the electrolyte and fluorinating agent was developed. Remarkably, different reaction pathways of indeno[1,2-c]furans, i.e., paired electrolysis and net oxidation, are operative in a batch reactor and a continuous-flow microreactor to afford the corresponding gem-difluorinated indanones and indenones, respectively.

本研究开发了一种茚并[1,2-c]呋喃的电化学宝石二氟化反应,其电解质和氟化剂均为市售且易于使用的三乙胺三氢氟酸。值得注意的是,茚并[1,2-c]呋喃的不同反应途径,即配对电解和净氧化,可在间歇反应器和连续流微反应器中分别进行,从而得到相应的宝石二氟化茚酮和茚酮。
{"title":"Batch and Continuous-Flow Electrochemical Geminal Difluorination of Indeno[1,2-<i>c</i>]furans.","authors":"Guo-Cai Yuan, Fang-Ling Gao, Kang-Wei Liu, Minggang Li, Yuqi Lin, Ke-Yin Ye","doi":"10.1021/acs.orglett.4c02235","DOIUrl":"10.1021/acs.orglett.4c02235","url":null,"abstract":"<p><p>An electrochemical <i>gem</i>-difluorination of indeno[1,2-<i>c</i>]furans using commercially available and easy-to-use triethylamine trihydrofluoride as both the electrolyte and fluorinating agent was developed. Remarkably, different reaction pathways of indeno[1,2-<i>c</i>]furans, i.e., paired electrolysis and net oxidation, are operative in a batch reactor and a continuous-flow microreactor to afford the corresponding <i>gem</i>-difluorinated indanones and indenones, respectively.</p>","PeriodicalId":54,"journal":{"name":"Organic Letters","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141537186","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Catalyst-Free, Zn-Mediated Decarboxylative Coupling of Chlorostibines to Access Alkylstibines with Stable C(sp3)-Sb Bonds. 无催化剂、锌介导的氯代二苯乙烯脱羧偶联,获得具有稳定 C(sp3)-Sb 键的烷基二苯乙烯。
IF 4.9 1区 化学 Q1 CHEMISTRY, ORGANIC Pub Date : 2024-07-19 Epub Date: 2024-07-05 DOI: 10.1021/acs.orglett.4c02132
Liyuan Le, Huifan Zeng, Wenjun Zhou, Niu Tang, Shuang-Feng Yin, Nobuaki Kambe, Renhua Qiu

Herein, decarboxylative C(sp3)-Sb coupling of aliphatic carboxylic acid derivatives with chlorostibines to access alkylstibines has been achieved. This catalyst-, ligand-, and base-free approach using zinc as a reductant affords various kinds of benzyldiarylstibines and other monoalkyldiarylstibines and tolerates various functional groups, including chlorine, bromine, hydroxyl, amide, sulfone, and cyano groups. The late-stage modification and the gram-scale experiments illustrate its potential application.

在此,我们实现了脂肪族羧酸衍生物与氯代二苯乙烯的脱羧 C(sp3)-Sb 偶联,从而获得烷基二苯乙烯。这种以锌为还原剂的无催化剂、无配体、无碱的方法可以得到各种苄基二芳基丝氨酸和其他单烷基二芳基丝氨酸,并可容忍各种官能团,包括氯、溴、羟基、酰胺、砜和氰基。后期改性和克级实验说明了它的潜在应用价值。
{"title":"Catalyst-Free, Zn-Mediated Decarboxylative Coupling of Chlorostibines to Access Alkylstibines with Stable C(sp<sup>3</sup>)-Sb Bonds.","authors":"Liyuan Le, Huifan Zeng, Wenjun Zhou, Niu Tang, Shuang-Feng Yin, Nobuaki Kambe, Renhua Qiu","doi":"10.1021/acs.orglett.4c02132","DOIUrl":"10.1021/acs.orglett.4c02132","url":null,"abstract":"<p><p>Herein, decarboxylative C(sp<sup>3</sup>)-Sb coupling of aliphatic carboxylic acid derivatives with chlorostibines to access alkylstibines has been achieved. This catalyst-, ligand-, and base-free approach using zinc as a reductant affords various kinds of benzyldiarylstibines and other monoalkyldiarylstibines and tolerates various functional groups, including chlorine, bromine, hydroxyl, amide, sulfone, and cyano groups. The late-stage modification and the gram-scale experiments illustrate its potential application.</p>","PeriodicalId":54,"journal":{"name":"Organic Letters","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141537187","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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