Article
Chemistry, Multidisciplinary
Chengsen Cui, Mingji Dai
Summary: We present a highly efficient and convergent strategy for synthesizing UCS1025A and its diastereomer tetra-epi-UCS1025A. UCS1025A is a representative member of the naturally occurring pyrrolizidinone polyketides, some of which exhibit potent antibacterial, antifungal, and anticancer activities. Our approach involves a tandem carbonylative Stille cross coupling and Diels-Alder reaction to form a key C-C bond and construct the trans-decalin system. The process uses carbon monoxide as a linchpin to connect a vinyl triflate and a vinylstannane, resulting in the desired enone moiety for subsequent intramolecular Diels-Alder cyclization. Additionally, our synthesis provides a versatile method for synthesizing other pyrrolizidinone-containing polyketides.
CHINESE JOURNAL OF CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Dongseok Jang, Minchul Choi, Jinglong Chen, Chulbom Lee
Summary: The first enantioselective total synthesis of (+)-garsubellin A was reported, showcasing high synthetic efficiency and simplicity. The synthesis relied on stereoselective construction of a cyclohexanone framework and double conjugate addition to promote aldol cyclization.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Medicinal
Gabriele Laudadio, Maximilian D. Palkowitz, Tamara El-Hayek Ewing, Phil S. Baran
Summary: This article introduces the versatile applications of carboxylic acids in medicinal chemistry, as well as the possibility of using radical reactions to construct C-C bonds. This emerging field contributes to the rapid access of chemical space valuable to modern medicinal chemistry.
ACS MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Chemistry, Organic
Hai-Yang Zhao, Minqi Zhou, Xingang Zhang
Summary: A palladium-catalyzed carbonylative cross-coupling of difluoroalkyl halides with alkyl-9-BBN under 1 atm of CO has been developed, showing broad substrate scope and high functional group tolerance, even towards complex pharmaceuticals. Preliminary mechanistic studies suggest a radical pathway is involved in the reaction.
Article
Chemistry, Multidisciplinary
Haifeng Chen, Huifeng Yue, Chen Zhu, Magnus Rueping
Summary: This study describes a nickel-catalyzed three-component reductive carbonylation reaction for the synthesis of aryl-alkyl ketones. Ethyl chloroformate is used as a safe and readily available source of CO, providing an efficient and practical alternative. Experimental and mechanistic studies provide insight into the complexity and sequence of the reaction.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Review
Biochemistry & Molecular Biology
Shaheera Tabassum, Ameer Fawad Zahoor, Sajjad Ahmad, Razia Noreen, Samreen Gul Khan, Hamad Ahmad
Summary: Cross-coupling reactions are powerful tools for synthesizing natural products, with Suzuki, Negishi, Heck, Sonogashira, and Stille reactions being commonly used in total synthesis. This review highlights the significance of these reactions in organic synthesis and provides examples of incorporating multiple types of cross-coupling reactions in the synthesis of natural products.
MOLECULAR DIVERSITY
(2022)
Article
Chemistry, Medicinal
Wei Liu, James Mulhearn, Bo Hao, Santiago Canellas, Stefaan Last, Jose Enrique Gomez, Alexander Jones, Alexander De Vera, Kiran Kumar, Raquel Rodriguez, Lars Van Eynde, Iulia I. Strambeanu, Scott E. Wolkenberg
Summary: We report the development of an automated deoxygenative C-(sp(2))-C-(sp(3)) coupling of aryl bromide with alcohols, enabling parallel medicinal chemistry. An automated workflow involving solid-dosing and liquid-handling robots was developed to achieve high throughput and consistency. The protocol has the potential to substantially increase the impact of C-(sp(2))-C-(sp(3)) cross-coupling in drug discovery by accessing the rich diversity of alcohols.
ACS MEDICINAL CHEMISTRY LETTERS
(2023)
Article
Chemistry, Multidisciplinary
Shi-Hui Shi, Jian Wei, Chun-Miao Liang, Huan Bai, Hai-Tao Zhu, Yantu Zhang, Feng Fu
Summary: We reported a strategy for the functionalization of quinoxalinones via an environmentally friendly electrochemical method, achieving C2-O sulfonylation of quinoxalinones. A wide range of 2-sulfonyloxylated quinoxaline derivatives were obtained with good yields and functional-group tolerance under mild conditions without additional oxidants. The utility of this method was demonstrated in gram-scale preparation and synthesis of bioactive molecules based on 2-substituted quinoxaline.
CHEMICAL COMMUNICATIONS
(2022)
Article
Chemistry, Multidisciplinary
Yu-Ci Chang, Zhicheng Jin, Ke Li, Jiajing Zhou, Wonjun Yim, Justin Yeung, Yong Cheng, Maurice Retout, Matthew N. Creyer, Pavla Fajtova, Tengyu He, Xi Chen, Anthony J. O'Donoghue, Jesse V. Jokerst
Summary: Electrostatic interactions play a crucial role in colloidal assembly. The Schulze-Hardy rule states that nanoparticles tend to coagulate more when exposed to counterions with higher charge valence. This study investigates how the Schulze-Hardy rule functions when using more complex charge carriers instead of simple electrolytes. The researchers designed cationic peptides with different valencies and found that their charge screening behaviors on anionic gold nanoparticles followed the six-power relationship in the Schulze-Hardy rule. This discovery also led to a simple and effective strategy for visually measuring SARS-CoV-2 main protease (M-pro). By understanding the fundamental disassembly of nanoparticles based on the Schulze-Hardy rule, this work offers potential in designing versatile substrates for colorimetric sensing of other proteases.
Article
Acoustics
Sasadhar Majhi
Summary: Total synthesis is a method for preparing complex natural products from simple materials, which plays a crucial role in confirming complex structures and preparing rare bioactive substances. The use of ultrasound as a non-polluting energy source in the synthesis of bioactive natural products highlights its potential in sustainable and pharmaceutical chemistry.
ULTRASONICS SONOCHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Ekta Verma, Shailendra Patil, Asmita Gajbhiye
Summary: This study discovered a breakthrough method for N-benzylation using diisopropylamine and tetra butyl ammonium bromide, which achieves high efficiency and purity with no byproducts.
Article
Chemistry, Multidisciplinary
Johanne Ling, Antoine Bruneau-Voisine, Guillaume Journot, Gwilherm Evano
Summary: In this study, a general copper-catalyzed carbonylative cross-coupling between amines and alkyl iodides was reported. The reaction showed good efficiency and broad substrate scope, making it potentially valuable for industrial applications.
CHEMISTRY-A EUROPEAN JOURNAL
(2022)
Article
Chemistry, Organic
Morgan J. Cordell, Matt R. Adams, Jean-Francois Vincent-Rocan, John G. Riley
Summary: By utilizing photo-redox catalysis in flow, the newly marketed drug entrectinib was successfully synthesized in a shorter and more efficient way. The study identified that more electron deficient aryl-halides achieved higher conversion rates, shedding light on the important role of electron density in the reaction. The research also discovered a scalable synthesis route using photo-redox catalysis in flow, highlighting the significance and practicality of flow chemistry in the pharmaceutical industry.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Organic
Tobias Babl, Oliver Reiser
Summary: The first enantioselective synthesis of (S)-meptazinol in 14 steps from a commercially available compound and the formal synthesis of two anti-Alzheimer's agents are reported. A novel ring expansion reaction provides an effective entry to 3,3-disubstituted azepanes that represent the core for a variety of approved drugs.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
Review
Chemistry, Multidisciplinary
Suman Chakrabarty, Evan O. Romero, Joshua B. Pyser, Jessica A. Yazarians, Alison R. H. Narayan
Summary: The total synthesis of structurally complex natural products remains an exciting area of research, with recent advancements in biocatalysis allowing for the application of enzymes in constructing complex molecules. The utilization of enzymes alongside small molecule-based approaches has enabled concise chemoenzymatic routes to natural products, demonstrating the potential for selective oxidation reactions and late-stage diversification of complex scaffolds.
ACCOUNTS OF CHEMICAL RESEARCH
(2021)
Article
Chemistry, Multidisciplinary
Eva Korytiakova, Ewelina Kaminska, Markus Mueller, Thomas Carell
Summary: The synthesis of a fluorinated fdC feeding probe allowed for the study of direct deformylation to F-dC, providing insights into the Tdg-independent removal process. The research demonstrated deformylation occurring in both stem cells and different somatic cell types. Additionally, active demethylation was investigated in a non-dividing neurogenin-inducible system of iPS cells differentiating into bipolar neurons.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Biochemistry & Molecular Biology
Simon Veth, Adrian Fuchs, Dilara Oezdemir, Clemens Dialer, David Jan Drexler, Fabian Knechtel, Gregor Witte, Karl-Peter Hopfner, Thomas Carell, Evelyn Ploetz
Summary: The cGAS-STING pathway plays a crucial role in sensing cytosolic DNA. Research on the development of fluorescent moieties and synthesis of fluorescent molecules for detection is important for the therapeutic potential of this pathway.
Article
Chemistry, Multidisciplinary
Franziska R. Traube, Natercia F. Bras, Wynand P. Roos, Corinna C. Sommermann, Tamara Diehl, Robert J. Mayer, Armin R. Ofial, Markus Mueller, Hendrik Zipse, Thomas Carell
Summary: 5-Aza-2'-deoxycytidine is a drug used to treat myelodysplastic syndrome or acute myeloid leukemia by targeting epigenetic regulation. A recently developed carbocyclic AzadC analogue shows stronger anti-proliferative effects and induces more DNA damage in cancer cells compared to AzadC, making it a promising next generation epigenetic drug.
CHEMISTRY-A EUROPEAN JOURNAL
(2022)
Article
Multidisciplinary Sciences
Felix Mueller, Luis Escobar, Felix Xu, Ewa Wegrzyn, Milda Nainyte, Tynchtyk Amatov, Chun-Yin Chan, Alexander Pichler, Thomas Carell
Summary: The RNA world hypothesis suggests that life evolved from self-replicating RNA molecules. However, the transition from the RNA world to the dominance of proteins as catalysts remains a mystery. Recent research has shown that non-canonical RNA bases, considered relics of the RNA world, can directly facilitate peptide synthesis on RNA, indicating the existence of an early RNA-peptide world.
Article
Chemistry, Multidisciplinary
Felix Xu, Antony Crisp, Thea Schinkel, Romeo C. A. Dubini, Sarah Huebner, Sidney Becker, Florian Schelter, Petra Rovo, Thomas Carell
Summary: The study suggests that isoxazole nucleosides may be precursors of RNA, which is significant for understanding the evolutionary origin of RNA.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Biochemical Research Methods
Eva S. Schoenegger, Antony Crisp, Markus Mueller, Jessica Fertl, Sascha Serdjukow, Stefano Croce, Michael Kollaschinski, Thomas Carell, Thomas Frischmuth
Summary: Researchers developed a novel click chemistry-based method for generating and amplifying full-length cDNA libraries from total RNA, without the need for problematic template-switching reactions. This method enables amplification of previously inaccessible transcripts and provides larger insert sizes compared to the state-of-the-art click chemistry-based technique, PAC-seq.
BIOCONJUGATE CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Luis Montiel, Fabio Spada, Antony Crisp, Sascha Serdjukow, Thomas Carell, Thomas Frischmuth
Summary: Biorthogonal labelling using fluorescent small molecules is crucial for diagnostic and biomedical applications. A new synthetic procedure was developed to produce pH-insensitive rhodamine dyes with outstanding brightness, outperforming other common dyes in DNA fluorescent imaging. Additionally, the fluorescence properties of these dyes were further explored using dendrimers with multiple fluorescein or rhodamine units, revealing fluorescence self-quenching effects.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Multidisciplinary Sciences
Maria Arroyo, Florian D. Hastert, Andreas Zhadan, Florian Schelter, Susanne Zimbelmann, Cathia Rausch, Anne K. Ludwig, Thomas Carell, M. Cristina Cardoso
Summary: This study reveals that Tet1 and its short isoform Tet1s have different localization during DNA replication, affecting cytosine modification levels. Tet1s interacts with CRL4(VprBP), ubiquitinated, and recruited to late replicating heterochromatin by Uhrf1, leading to 5-methylcytosine oxidation and chromatin decondensation.
NATURE COMMUNICATIONS
(2022)
Review
Chemistry, Multidisciplinary
Bethany Searle, Markus Mueller, Thomas Carell, Andrew Kellett
Summary: The discovery of epigenetic bases has greatly impacted our understanding of disease and development. One of the most studied epigenetic marks is the modification of cytosines at the 5 position. Determining the spatiotemporal distribution of these modifications within the genome is crucial for gaining insight into their biological significance. While third-generation sequencing platforms have the potential to directly detect epigenetic modifications, chemical or enzymatic derivatisation currently provides the most reliable method. This Review discusses techniques available for the detection of cytosine modifications on third-generation platforms.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Correction
Multidisciplinary Sciences
Maria Arroyo, Florian D. Hastert, Andreas Zhadan, Florian Schelter, Susanne Zimbelmann, Cathia Rausch, Anne K. Ludwig, Thomas Carell, M. Cristina Cardoso
NATURE COMMUNICATIONS
(2023)
Article
Chemistry, Multidisciplinary
Johannes N. Singer, Felix M. Mueller, Ewa Wegrzyn, Christina Hoelzl, Hans Hurmiz, Chuyi Liu, Luis Escobar, Thomas Carell
Summary: RNA is a molecule that plays a significant role in the origin of life as it can store genetic information and catalyze reactions. Recent studies have shown that RNA can form chimeras with amino acids, combining the information-coding properties of RNA with the catalytic potential of amino acids, which may have been the structures from which life emerged. This study reports a prebiotic chemistry method that allows the loading of nucleosides and RNAs with amino acids, paving the way for RNA-based peptide synthesis in a hypothetical RNA-peptide world.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Biochemistry & Molecular Biology
Eva S. Schoenegger, Antony Crisp, Marco Radukic, Jonas Burmester, Thomas Frischmuth, Thomas Carell
Summary: Post-synthetic modification of nucleic acid structures with clickable functionality is a versatile tool that improves the performance and applicability of nucleic acids. This study presents a simple and feasible technology to modify DNA and RNA strands at both ends. This method helps to synthesize highly functionalized oligonucleotides, enhancing their therapeutic and diagnostic applications.
Article
Biochemistry & Molecular Biology
Monika Witzenberger, Sandra Burczyk, David Settele, Wieland Mayer, Luisa M. Welp, Matthias Heiss, Mirko Wagner, Thomas Monecke, Robert Janowski, Thomas Carell, Henning Urlaub, Stefanie M. Hauck, Aaron Voigt, Dierk Niessing
Summary: 5-Methyluridine (m(5)U) is a common RNA modification in cytosolic tRNA, and tRNA methyltransferase 2 homolog A (hTRMT2A) is the enzyme responsible for m(5)U formation at position 54 of tRNA. Through structural and sequence analysis, it has been determined that hTRMT2A achieves specificity for tRNA modification through a combination of binding preference and the presence of a uridine at position 54. Additionally, hTRMT2A has been found to interact with proteins involved in RNA biogenesis and its knockdown has been shown to reduce translation fidelity.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Mark Helm, Markus T. Bohnsack, Thomas Carell, Alexander Dalpke, Karl-Dieter Entian, Ann Ehrenhofer-Murray, Ralf Ficner, Christian Hammann, Claudia Ho''bartner, Andres Ja''schke, Albert Jeltsch, Stefanie Kaiser, Roland Klassen, Sebastian A. Leidel, Andreas Marx, Mario Mo''rl, Jochen C. Meier, Gunter Meister, Andrea Rentmeister, Marina Rodnina, Jean-Yves Roignant, Raffael Schaffrath, Peter Stadler, Thorsten Stafforst
Summary: This article describes the impact and subsequent effects of the DFG-funded priority program SPP1784 on the field of nucleic acid modifications. The program has facilitated interdisciplinary collaborations and contributed to the development of the nucleic acid chemistry community. The extension of funding during the COVID-19 pandemic has led to increased interest and research in the field of RNA and RNA modifications, particularly in the context of vaccination campaigns against SARS-CoV-2.
ACS CHEMICAL BIOLOGY
(2023)
Article
Genetics & Heredity
Paraskevi Karousi, Martina Samiotaki, Manousos Makridakis, Jerome Zoidakis, Diamantis C. Sideris, Andreas Scorilas, Thomas Carell, Christos K. Kontos
Summary: This study investigates the role of 3'-tRF-Cys(GCA) in gene expression regulation in HEK-293 cells and finds that it can regulate gene expression by affecting multiple cellular pathways. Additionally, the study identifies the direct interaction between 3'-tRF-Cys(GCA) and thymopoietin and its modulation of the protein's levels.
FUNCTIONAL & INTEGRATIVE GENOMICS
(2023)
