Article
Chemistry, Organic
Kartic Manna, Ranjan Jana
Summary: We describe a mild and highly selective palladium-catalyzed cross-electrophile coupling between aromatic diazonium salts and aryl iodides or diaryliodonium salts in a water-ethanol (2:1) medium. Mechanistic studies revealed the importance of ethanol in generating an active Pd(0) catalyst, and the counterion of the diazonium salt promotes the formation of a cationic Pd(II) species that facilitates subsequent oxidative addition to aryl iodides/diaryliodonium salts. The presence of silver(I) salt is crucial for maintaining the catalytic activity of palladium by removing iodide ions as precipitates.
Article
Chemistry, Multidisciplinary
Mo Chen, Austin M. Ventura, Soumik Das, Ammar F. Ibrahim, Paul M. Zimmerman, John Montgomery
Summary: Current methodologies for metal-catalyzed cross-couplings require the installation of reactive functional groups on both reaction partners in advance. In contrast, C-H functionalization approaches show potential in simplifying the substrates required; however, challenges such as low reactivity and similar reactivity of different C-H bonds add complexity. This study describes an oxidative cross dehydrogenative coupling of α-amino C(sp(3))-H bonds and aldehydes to produce ketone derivatives using an unusual reaction medium that simultaneously utilizes di-tert-butyl peroxide as an oxidant and zinc metal as a reductant. The method has a broad substrate scope and offers an attractive approach for accessing α-amino ketones through the formal acylation of C-H bonds adjacent to nitrogen in N-heterocycles. Experimental investigation and computational modeling provide evidence for a mechanistic pathway involving cross-selective nickel-mediated cross-coupling of α-amino radicals and acyl radicals.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Article
Chemistry, Organic
Oliver M. Griffiths, Henrique A. Esteves, Yiding Chen, Karin Sowa, Oliver S. May, Peter Morse, David C. Blakemore, Steven Ley
Summary: Executing photoredox reactions in flow can improve reaction concentration, reduce reaction time, achieve better yields, facilitate catalyst preparation, and expand substrate scope, demonstrating broad applicability.
JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Chemistry, Organic
Naoki Oku, Masahiro Murakami, Tomoya Miura
Summary: This article introduces a Suzuki-Miyaura cross-coupling reaction of alpha-chloroacetates or alpha-chloroacetamides with arylboronic acids under visible-light irradiation, providing a mild method for the synthesis of alpha-arylacetates and alpha-arylacetamides. Additionally, the authors successfully synthesized a key intermediate of the plant hormone auxin, indole-3-acetic acid derivative, from 1-Boc-indole in two steps by combining an iridium-catalyzed C-H borylation and a palladium-catalyzed cross-coupling reaction.
Article
Chemistry, Multidisciplinary
Ji-Hang Xu, Zi-Kui Liu, Yan-Liu Tang, Yang Gao, Xiao-Qiang Hu
Summary: An unprecedented ring-opening cross-coupling of 1,2-oxazetidines with arylboronic acids using copper catalysis has been achieved. This reaction offers simple operation, inexpensive catalyst, broad scope, and high regioselectivity, leading to a wide range of aminomethylation products. Furthermore, the obtained products can be further transformed and bioactive acids can be modified.
CHEMICAL COMMUNICATIONS
(2022)
Article
Chemistry, Organic
Yushi Tan, Wu Xuekun, Ya-Ping Han, Yuecheng Zhang, Hong-Yu Zhang, Jiquan Zhao
Summary: An efficient and convenient method for synthesizing 6-oxyalkylated 1,2,4-triazine-3,5(2H, 4H)-diones has been developed using a visible-light-induced cross-dehydrogenative coupling reaction. This reaction allows for a wide range of functional groups and uses a cheap and low-toxic photocatalyst and air as an oxidant. Additionally, the reaction can be driven by sunlight as a clean energy resource and has demonstrated utility in gram-scale reactions and the synthesis of key intermediates for bioactive molecules.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Organic
Patrick Cyr, Eve-Marline Joseph-Valcin, Patrick Boissarie, Bruno Simoneau, Anne Marinier
Summary: This study presents a copper-catalyzed method for the N-1-selective arylation of 3-aminoindazoles using readily accessible aryl bromides as coupling partners, facilitating the synthesis of a variety of substituted 3-aminoindazoles. The methodology was also applied to other aminoazoles of interest to the pharmaceutical industry.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Zhuang Wang, Kaikai Niu, Yuxiu Liu, Hongjian Song, Qingmin Wang
Summary: A mild and convenient protocol for the synthesis of alpha-alkoxy isochroman derivatives has been reported in this study. The electrochemical alpha-C(sp(3))-H/O-H cross-coupling reactions of isochromans and alcohols in the presence of benzoic acid were used, which facilitated the electro-oxidation process and increased the product yield. The desired coupling products were obtained in moderate to high yields.
CHEMICAL COMMUNICATIONS
(2022)
Article
Chemistry, Organic
Xiao-Wen Wang, Rui-Xue Li, Yang Deng, Ming-Qiu-Hao Fu, Ya-Nan Zhao, Zhi Guan, Yan-Hong He
Summary: This article proposes a new method for the direct hydroxylarylation of unactivated benzylic carbons (sp3/sp2/sp) without the need for pre-functionalized benzylic alcohols, aromatic aldehydes, or ketones. It features direct functionalization of unactivated benzylic C(sp3)-H bonds and benzylic sp2/sp-carbons, mild conditions (open air, room temperature), an environmentally friendly procedure (without any external catalyst/mediator/additive), and direct access to sterically hindered alcohols from inexpensive and readily available alkyl/alkenyl/alkynylbenzenes. Mechanistic studies strongly support the proposed radical-radical cross-coupling between transient ketyl radicals and persistent radical anions. Gram-scale synthesis and diversification of drug derivatives demonstrate the practical potential of this protocol.
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Organic
Cui-Lian Zeng, Hao Wang, Di Gao, Zhen Zhang, Dong Ji, Wei He, Cheng-Kou Liu, Zhao Yang, Zheng Fang, Kai Guo
Summary: This study presents a green and gentle Minisci-type reaction method, in which the cross-dehydrogenative coupling of heteroarenes with aliphatic C(sp(3))-H bonds is achieved under visible-light irradiation. This method does not require oxidants or transition metal catalysts, and only the catalytic equivalent of CF3SO2Na and room temperature are needed to ensure an efficient reaction.
Article
Chemistry, Organic
Chunqi Jia, Nini Wu, Gang Li, Xiuling Cui
Summary: In this study, a new method for the oxidative meta-dehydrogenative allylation of arenes with alkenes has been successfully developed using Ru(PPh3)3Cl2 as a catalyst and DTBP as an oxidant. The results demonstrate that this method provides an efficient and practical strategy for the preparation of versatile meta-allylated arenes.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Ryota Sato, Tomoki Lida, Takaki Kanbara, Junpei Kuwabara
Summary: This Pd-catalysed cross-dehydrogenative coupling reaction allows the introduction of two polyfluoroarenes into simple polyaromatic hydrocarbons at sterically favourable positions. The investigation of the reaction mechanism revealed that the unique regioselectivity is determined by the reductive elimination step rather than the C-H bond cleavage step.
CHEMICAL COMMUNICATIONS
(2022)
Article
Chemistry, Organic
Tingzhi Lin, Yan-En Wang, Ning Cui, Miaohui Li, Rui Wang, Jiahui Bai, YiRan Fan, Dan Xiong, Fei Xue, Patrick J. Walsh, Jianyou Mao
Summary: A nickel-catalyzed cross-electrophile coupling reaction has been developed to generate a diverse array of ortho-arylated benzamide derivatives. The reaction shows good functional group tolerance and scalability.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Organic
Xianglong Chu, Yadi Niu, Xiaodong Wang, Yunliang Lin, Fuwei Li, Chen Ma
Summary: A rapid method for preparing a series of N-heteroarene fluorophores via palladium-catalyzed direct oxidative reactions has been developed, showing color-tunable emissions and high fluorescence quantum yields. The photophysical properties-structure relationship was systematically investigated, leading to the discovery of fluorophores with emissions ranging from 431-507 nm in CH2Cl2 and fluorescence quantum yields up to 91% in CH2Cl2.
SYNTHESIS-STUTTGART
(2021)
Article
Chemistry, Multidisciplinary
Hairong Lyu, Zuowei Xie
Summary: A unique approach to vertex-selective catalytic B-H amination has been developed, allowing the reaction to occur at either the B(3)- or B(4)-position in o-carboranes. By using different transition metal catalysts, the dehydrogenative BH/NH cross-coupling of o-carboranes and free amines has been achieved, resulting in a wide variety of B(3)- or B(4)-aminated o-carboranes with high regioselectivity.
CHEMICAL COMMUNICATIONS
(2022)
Article
Chemistry, Multidisciplinary
Maria Brunderova, Matous Kromer, Marta Vlkova, Michal Hocek
Summary: We designed and synthesized a chloroacetamide-linked 7-deaza-ATP substrate for T7 RNA polymerase, which was used to synthesize reactive RNA probes with one or more reactive modifications. The modified RNA probes reacted with thiol-containing molecules and cysteine- or histidine-containing peptides, forming stable covalent products. They also selectively reacted with RNA-binding proteins, forming cross-linked conjugates with high conversions due to proximity effect. Our modified nucleotide and RNA probes are promising tools for RNA (bio)conjugations or RNA proteomics applications.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Biochemical Research Methods
Miroslav Kuba, Radek Pohl, Tomas Kraus, Michal Hocek
Summary: Nucleosides and 2'-deoxyribonucleoside triphosphates (dNTPs) containing a bodipy fluorophore attached to position S of 2'-deoxycytidine were synthesized. They exhibited strong fluorescence and sensitivity to viscosity. The modified dNTPs served as substrates for DNA polymerases and were used for enzymatic synthesis of labeled DNA. The modified DNA probes acted as viscosity sensors, responding to protein binding. The dNTP with a longer linker was successfully transported into live cells and incorporated into genomic DNA, enabling DNA staining and imaging of DNA synthesis.
BIOCONJUGATE CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Vaclav Houska, Egor Ukraintsev, Jaroslav Vacek, Jiri Rybacek, Lucie Bednarova, Radek Pohl, Irena G. Stara, Bohuslav Rezek, Ivo Stary
Summary: The synthesis of helically chiral macrocycles composed of dibenzo[5]helicene units and trans-stilbene-4,4'-diyl linkers is reported. Different stereoisomers of these macrocycles were obtained through chiral resolution. The self-assembly of these macrocycles into long 1D molecular stripes in ordered 2D nanocrystals was studied using AFM.
Article
Biochemical Research Methods
Ambra Spampinato, Erika Kuzmova, Radek Pohl, Veronika Sykorova, Milan Vrabel, Tomas Kraus, Michal Hocek
Summary: A series of modified dNTPs with different linkers were designed and synthesized as substrates for DNA polymerase. The reactivity of these modified nucleotides and DNA was systematically tested and compared in click reactions. The longer linker was found to be crucial for efficient labeling. These modified dNTPs were transported into live cells and successfully used for staining DNA and imaging DNA synthesis within short time periods. This method provides a new approach for in cellulo metabolic labeling and imaging of DNA synthesis that overcomes previous limitations.
BIOCONJUGATE CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Catherine Mulholland, Ivana Jestrabova, Arghya Sett, Marek Ondrus, Veronika Sykorova, C. Lorena Manzanares, Oliver Simoncik, Petr Muller, Michal Hocek
Summary: The authors describe the selection of hydrophobic 7-phenylbutyl-7-deazaadenine-modified DNA aptamers against Heat Shock Protein 70 using PEX and magnetic bead-based SELEX. The modified aptamers showed higher binding affinity to Hsp70 than their natural counterparts and have potential for diagnostic or therapeutic applications.
COMMUNICATIONS CHEMISTRY
(2023)
Article
Chemistry, Analytical
David Kodr, Mayreli Ortiz, Veronika Sykorova, Cansu Pinar Yenice, Zbigniew J. Lesnikowski, Ciara K. O'Sullivan, Michal Hocek
Summary: The previous approach of orthogonal multipotential redox coding only allowed analysis of relative nucleotide composition of short DNA stretches. In this study, two methods for normalization of electrochemical readout were presented, enabling determination of total nucleotide composition. The first method involved the presence or absence of an internal standard in the DNA primer, while the second method utilized a viologen-modified primer acting as a reference label for signal normalization. Both methods accurately analyzed DNA sequences and demonstrated potential for targeted DNA sequence analysis.
ANALYTICAL CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Miroslav Kuba, Petro Khoroshyy, Martin Lepsik, Erika Kuzmova, David Kodr, Tomas Kraus, Michal Hocek
Summary: A modified dC(TO)TP was designed and synthesized with a thiazole orange moiety tethered via an oligoethylene glycol linker. It could be incorporated into DNA by DNA polymerases in vitro and live cells. The fluorescence lifetime of the thiazole orange moiety differed significantly when dC(TO)TP was incorporated into DNA compared to its non-incorporated forms. By delivering dC(TO)TP into live U-2 OS cells using a synthetic nucleoside triphosphate transporter, it enabled real-time detection and monitoring of cells actively synthesizing DNA from the beginning.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Organic
Chao Yang, Michal Tichy, Lenka Postova Slavetinska, Enzo Vaiedelich, Sona Gurska, Petr Dzubak, Marian Hajduch, Michal Hocek
Summary: This study reports the design and synthesis of a series of benzofuro-fused 7-deazapurine nucleosides and ribonucleosides. The target compounds were successfully synthesized through multiple reactions, and showed moderate to weak cytostatic activity and interesting fluorescence properties.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Natalia Kuprikova, Marek Ondrus, Lucie Bednarova, Miguel Riopedre-Fernandez, Lenka Postova Slavetinska, Veronika Sykorova, Michal Hocek
Summary: Researchers designed and synthesized a set of new DNA nucleotide derivatives, which were successfully used for DNA modification and hypermodification. The study found that one to two modified nucleotides could achieve exponential amplification in PCR, while three to four modified nucleotides only achieved linear amplification. In addition, hypermodified DNA exhibited a different secondary structure.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Chemistry, Multidisciplinary
Mayreli Ortiz, Miriam Jauset-Rubio, Olivia Trummer, Ines Foessl, David Kodr, Josep Lluis Acero, Mary Luz Botero, Phil Biggs, Daniel Lenartowicz, Katerina Trajanoska, Fernando Rivadeneira, Michal Hocek, Barbara Obermayer-Pietsch, Ciara K. O'Sullivan
Summary: A generic platform was developed for cost-effective and rapid electrochemical SNP genotyping from fingerprick blood samples, enabling early diagnosis of osteoporosis. The platform utilizes isothermal solid-phase primer elongation with ferrocene-labeled nucleoside triphosphates, allowing for targeted genotyping of SNPs associated with osteoporosis. The system was validated using real blood samples, with results matching those from Taqman SNP genotyping assays and Sanger sequencing. The platform is highly versatile and has the potential to be deployed in an automated device for targeted SNP genotyping.
ACS CENTRAL SCIENCE
(2023)
Article
Chemistry, Multidisciplinary
Ivana Jestrabova, Lenka Postova Slavetinska, Michal Hocek
Summary: We designed and synthesized a series of novel nucleoside phosphoramidites for the solid-phase synthesis of modified oligonucleotides. The hybridization properties of these modified oligonucleotides were studied, and they have potential for the synthesis of highly modified functional nucleic acid-based polymers.
Article
Chemistry, Multidisciplinary
Vladimir Motornov, Radek Pohl, Blanka Klepetarova, Petr Beier
Summary: Elusive N-acyl-1,2,3-triazoles formed by direct acylation of NH-1,2,3-triazoles were isolated and characterized. Thermodynamic N2 isomers were found to be preferred. Direct evidence of interconversion between N1- and N2-acyltriazoles confirmed their usefulness in denitrogenative transformations. An efficient synthesis of enamido triflates from NH-triazoles via N2-acyl-1,2,3-triazole intermediates was developed.
CHEMICAL COMMUNICATIONS
(2023)
Article
Chemistry, Multidisciplinary
David Kodr, Erika Kuzmova, Radek Pohl, Tomas Kraus, Michal Hocek
Summary: We designed and synthesized lipid-modified dNTPs, which served as substrates for DNA polymerase and could be incorporated simultaneously into the DNA strand. These lipid-ON probes showed enhanced membrane anchoring efficiency and better stability in the cell membrane compared to commonly studied ON analogues. The probes were detected at the cell surface even after 24 hours, indicating their long-lasting effect.
Article
Chemistry, Multidisciplinary
Anna Kovalova, Vit Prouza, Martin Zavrel, Miroslav Hajek, Rastislav Dzijak, Alzbeta Magdolenova, Radek Pohl, Zdenek Voburka, Kamil Parkan, Milan Vrabel
Summary: This study presents a method for identifying lectin-binding ligands with low micromolar affinity by screening synthetic click glycopeptide libraries. The selected glycopeptides showed enhanced binding potency to the target lectins compared to the starting sugar moieties. This approach offers a promising alternative means of discovering ligands for galectins and other carbohydrate-binding proteins.