Article
Chemistry, Organic
Vladimir V. Voronin, Maria S. Ledovskaya, Konstantin S. Rodygin, Valentine P. Ananikov
Summary: This work presents a universal synthetic approach for the synthesis of D-2-labeled nitrogen heterocycles through cycloaddition reactions using in situ generated dideuteroacetylene. By using 1,4-dioxane as a solvent, the method allowed for high levels of deuteration up to 99%. It was demonstrated to be suitable for the synthesis of various D-2-labeled heterocycles such as triazoles, isoxazoles, pyrazoles, and pyridazines.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Chemistry, Organic
Merlin Kleoff, Lisa Boeser, Linda Baranyi, Philipp Heretsch
Summary: A metal-free synthesis method for benzotriazoles in flow using azides and in situ generated arynes is reported. The modular access to benzotriazoles is provided by employing different substitution patterns of the azide and aryne coupling partners. The safety profile of the process is improved by minimizing thermal strain of hazardous azides and accumulation of reactive intermediates through short reaction times in flow. The scalability of the reaction is also demonstrated.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Chemistry, Physical
Shazia Iqbal, Maria A. Khan, Almas Jabeen, Sammer Yousuf, Fatima Zafar, Farhana Batool, Muhammad Uzair Ganatra, Fatima Z. Basha
Summary: (Summary:)
Reactive oxygen species (ROS) play an important role in oxidative stress-related diseases. Anti-inflammatory agents are crucial in controlling excessive ROS production. This study designed new harmine-linked triazole compounds as potential anti-inflammatory agents and evaluated their activity and cytotoxicity.
JOURNAL OF MOLECULAR STRUCTURE
(2022)
Article
Chemistry, Multidisciplinary
Yuuya Kawasaki, Tomoya Hayashibara, Yuki Seto, Yutaro Taniguchi, Kazunobu Igawa, Katsuhiko Tomooka
Summary: DACN-NHS ester and DACN-maleimide are molecular connectors used for the synthesis of artificial hybrid biomolecules. The synthesis process involves two steps: connection to a corresponding molecule via the NHS ester or maleimide unit, followed by connection to a corresponding azido-containing molecule via DACN unit through copper-free-alkyne-azide-cycloaddition. The developed DACN derivatives, DACN-NHS ester and DACN-maleimide, have shown the ability to hybridize biomolecules.
CHEMICAL COMMUNICATIONS
(2023)
Article
Chemistry, Multidisciplinary
Hua-Feng He, Yuwan Wang, Chun Zou, Zheng Tu, Yongquan Xu, Junfeng Yin
Summary: A series of aryl cyclolactones bearing an exocyclized C=C bond were successfully constructed from aryl propargyl ether and o-iodibenzoic acid with moderate to good yields. The reaction showed excellent compatibility with diverse substituent groups and a concise mechanism was proposed based on substrate expansion and theoretical analysis.
Article
Chemistry, Multidisciplinary
Hua-Feng He, Yuwan Wang, Chun Zou, Zheng Tu, Yongquan Xu, Junfeng Yin
Summary: In this study, a series of aryl cyclolactones bearing an exocyclized C=C bond were successfully constructed using aryl propargyl ether and o-iodibenzoic acid as substrates. The reaction showed excellent compatibility and moderate to good yields. A concise mechanism was proposed based on substrate expansion and theoretical analysis.
Review
Biochemistry & Molecular Biology
Yaqi Zhao, Zhengqi Chai, Qingrui Zeng, Wen-Xiong Zhang
Summary: Nowadays, the click reaction of azides with alkynes has rapidly evolved as an efficient method for synthesizing 1,2,3-triazoles, an important class of N-containing heterocycles. While the 1,4-selective click reaction is well-established, the corresponding 1,5-selective reaction remains less explored, lacking a systematic review. This timely review summarizes the discovery and development of 1,5-selective click reactions of azides with alkynes for synthesizing 1,5-substituted 1,2,3-triazoles, including three types of reactions based on critical reactive intermediates and related mechanistic studies.
Article
Chemistry, Multidisciplinary
Selbi Keskin
Summary: The synthesis of a new class of compounds, 1-((1-phenyl-1H-1,2,3-triazol-4-yl)methyl)pyridin-2(1H)-one derivatives, starting from 2-hydroxynicotinic acid, was reported. The incorporation of a propargyl group into the nitrogen atom of pyridinones was achieved using K2CO3 as a base. Click cycloaddition reactions of alkynes with aryl azide derivatives in the presence of copper(I) catalyst were applied to obtain the target molecules.
Article
Chemistry, Organic
Cong Guan, Jiabin Yin, Jian Ji, Jinhua Liu, Xiang Wu, Tong Zhu, Shunying Liu
Summary: A regioselective electrochemical C-H amination method using easily accessible ethers has been developed to synthesize N (2)-substituted 1,2,3-triazole. Multiple substituents, including heterocycles, were well-tolerated, and 24 examples were obtained in moderate to good yields. Control experiments and DFT calculations revealed that the electrochemical synthesis occurs through a N-tosyl 1,2,3-triazole radical cation process, promoted by single-electron transfer from the lone pair electrons of the aromatic N-heterocycle, and the desulfonation is responsible for the high N (2)-regioselectivity.
Article
Biochemistry & Molecular Biology
Francesca Begini, Renata A. Balaguez, Allya Larroza, Eric F. Lopes, Eder Joao Lenardao, Claudio Santi, Diego Alves
Summary: This study presents a simple method to synthesize 4-arylselanyl-1H-1,2,3-triazoles from selenium-containing carbinols in a one-pot strategy, with moderate to good yields including quinoline and Zidovudine derivatives. One-pot protocols are essential for addressing concerns about waste production and solvent consumption, while also producing interesting by-products with alkynylselenium moieties connected to the triazole.
Article
Chemistry, Organic
Jose Laxio Arenas, Pascal Retailleau, Jean-Michel Gillet, Nour-Eddine Ghermani, Sandrine Ongeri, Benoit Crousse
Summary: The 5-fluoro triazole amino acid scaffold prepared by halogen exchange was successfully incorporated into peptides. The X-ray diffraction results revealed an important localization of the 5-fluoro triazole motif on one side of the negative potential surface, with the fluorine atom showing a cylindrical shape in its electron density deformation.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Alejandro Lopez-Ruiz, Mariano Ortega-Munoz, Francisco Santoyo-Gonzalez, Alicia Megia-Fernandez
Summary: The optimization of an undergraduate experiment for Organic Chemistry students is described, focusing on the concept of click chemistry. The preparation of a terminal fluorescent alkyne and an organic azide is reported, followed by their use in the Cu(I)-catalized azide-alkyne cycloaddition to obtain a novel molecule containing a triazole ring. The characterization of the product involves various techniques, allowing the students to practice a wide range of analytical methods.
Review
Chemistry, Organic
Rodrigo Ribeiro Alves Caiana, Cosme Silva Santos, Ronaldo Nascimento de Oliveira, Juliano Carlo Rufino Freitas
Summary: The use of 1H-1,2,3-triazoles has become an important scaffold in various technological sectors. This study conducted technological monitoring to understand the international scenario of 1H-1,2,3-triazoles based on filed patents, and examined the relationship between the number of patents and improved strategies for obtaining these compounds. The analysis revealed significant patent filings by prestigious multinational companies and identified the countries leading in patent registrations.
CURRENT ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Linwei Zeng, Jiaming Li, Sunliang Cui
Summary: In this study, we report a rhodium-catalyzed enantioselective click cycloaddition of azides and alkynes, which allows for the rapid and modular synthesis of atropisomeric triazoles with excellent yields and enantioselectivities. The process is mild, efficient, scalable, and has a broad substrate scope.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Multidisciplinary Sciences
Yawen You, Qingqing Deng, Yibo Wang, Yanjuan Sang, Guangming Li, Fang Pu, Jinsong Ren, Xiaogang Qu
Summary: This study reports on a DNA-based biocompatible, highly efficient, and precisely targeted copper nanocatalyst, which exhibits excellent catalytic activity and achieves efficient prodrug activation and antitumor effects in cancer cells.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Cody J. Hall, Mihwa Lee, Matthew P. Boarder, Alexandra M. Mangion, Anthony R. Gendall, Santosh Panjikar, Matthew A. Perugini, Tatiana P. Soares da Costa
Summary: Lysine biosynthesis in plants is regulated by the end product lysine, with DHDPS being the key enzyme in the diaminopimelate pathway. Knockouts of AtDHDPS1 and AtDHDPS2 in Arabidopsis thaliana result in different phenotypes, despite their high protein sequence identity. Structural differences, particularly in the key allosteric site residue Trp116, lead to differential lysine sensitivity and dissociation between the two isoforms, highlighting the impact of subtle protein structure variances on enzyme allostery in lysine biosynthesis.
Article
Biology
Tatiana P. Soares da Costa, Cody J. Hall, Santosh Panjikar, Jessica A. Wyllie, Rebecca M. Christoff, Saadi Bayat, Mark D. Hulett, Belinda M. Abbott, Anthony R. Gendall, Matthew A. Perugini
Summary: A novel herbicide target, DHDPS, was identified and inhibitors were found to have promising pre-emergence herbicidal activity against Arabidopsis thaliana, indicating a potential new approach for combating the global rise of herbicide-resistant weeds.
Article
Chemistry, Multidisciplinary
Christopher J. Smedley, Joshua A. Homer, Timothy L. Gialelis, Andrew S. Barrow, Rebecca A. Koelln, John E. Moses
Summary: Accelerated SuFEx click chemistry (ASCC) is an improved method for efficient and catalytic coupling of aryl and alkyl alcohols with various SuFExable hubs. The powerful combination of BTMG and HMDS reagents allows for lower catalyst loadings, providing a scalable method that is safe, efficient, and practical for modular synthesis. ASSC expands the accessibility of SuFEx products and will have significant applications in organic synthesis, medicinal chemistry, chemical biology, and materials science.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Biochemistry & Molecular Biology
Rebecca M. Christoff, Tatiana P. Soares da Costa, Saadi Bayat, Jessica K. Holien, Matthew A. Perugini, Belinda M. Abbott
Summary: This study reports the discovery of the first inhibitors of E. coli DHDPS from screening lead, which are not based on substrates from the lysine biosynthesis pathway. Over 50 thiazolidinediones and related analogues have been prepared to evaluate structure-activity relationships against this enzyme.
BIOORGANIC & MEDICINAL CHEMISTRY
(2021)
Article
Immunology
Bruce D. Wines, Halina M. Trist, Sandra Esparon, Rachael E. Impey, Graham A. Mackay, Robert K. Andrews, Tatiana P. Soares da Costa, Geoffrey A. Pietersz, Ross Baker, P. Mark Hogarth
Summary: The activation of Fc gamma RIIa by monoclonal antibodies requires interaction with both the Fab and Fc regions simultaneously on the same receptor molecules.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Multidisciplinary Sciences
Yunfei Cheng, Gencheng Li, Christopher J. Smedley, Marie -Claire Giel, Seiya Kitamura, Jordan L. Woehl, Giulia Bianco, Stefano Forli, Joshua A. Homer, John R. Cappiello, Dennis W. Wolan, John E. Moses, K. Barry Sharpless
Summary: Diversity Oriented Clicking (DOC) is a method for rapidly synthesizing functional libraries by combining classical and modern click chemistries. It involves modulating the assembly of compounds through chemical diversification of core SuFExable hubs, such as 2-Substituted-Alkynyl-1-Sulfonyl Fluorides (SASFs). The stereoselective Michael-type addition reactions from SASF hubs, including reactions with secondary amines, carboxylates, 1H-1,2,3-triazole, and halides, provide high yielding beta-substituted alkenyl sulfonyl fluorides as single isomers with minimal purification. These compounds show potential as covalent inhibitors of human neutrophil elastase, demonstrating the biological function aspect of click chemistry.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biochemistry & Molecular Biology
Zoe Day, Alyce J. Mayfosh, Marie-Claire Giel, Yuning Hong, Scott A. Williams, Jascinta P. Santavanond, Thomas F. Rau, Ivan K. Poon, Mark D. Hulett
Summary: This study presents a novel platform for solubilizing fatty acids using amino acids and investigates the tumoricidal activity and mechanism of undecylenic acid. The results demonstrate that the GS-1 formulation, a combination of undecylenic acid and L-Arginine, induces concentration-dependent tumor cell death through a pro-apoptotic mechanism. GS-1 localizes to lipid droplets intracellularly and is taken up by cells via Fatty Acid Transport Protein 2 (FATP2). These findings contribute to the emerging field of fatty acids as potential anti-cancer therapeutics.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Multidisciplinary
Christopher J. Smedley, Marie-Claire Giel, Thomas Fallon, John E. Moses
Summary: In this study, we present a method for synthesizing a stable precursor to ethene-1,1-disulfonyl difluoride (EDSF) and demonstrate its use in the preparation of various functionalized 4-membered ring carbocycles. These carbocycles are important structural motifs found in bioactive natural products and pharmaceutically relevant small molecules. We also show that the novel cyclobutene cores can be diversified through selective click chemistry, yielding high-efficiency sulfonate ester products. DFT calculations provide mechanistic insights into the reaction pathway.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Multidisciplinary Sciences
Joshua A. Homer, Long Xu, Namitharan Kayambu, Qinheng Zheng, Eun Joung Choi, Byeong Moon Kim, K. Barry Sharpless, Han Zuilhof, Jiajia Dong, John E. Moses
Summary: SuFEx is a click reaction for rapid synthesis and discovery of functional molecules. This Primer discusses the essential elements of SuFEx operation, catalysis, and SuFExable connective hubs, as well as explores its applications in drug development, polymer science, and biochemistry. It also examines the potential limitations and promising prospects of this versatile click reaction.
NATURE REVIEWS METHODS PRIMERS
(2023)
Article
Biochemistry & Molecular Biology
Timothy L. Gialelis, Zifei Wang, Joshua A. Homer, Wen-Hsuan Yang, Taemoon Chung, Qingting Hu, Christopher J. Smedley, Nitin J. Pawar, Nitinkumar S. Upadhyay, David A. Tuveson, Scott K. Lyons, Michael J. Lukey, John E. Moses
Summary: A concise semi-synthesis of (-)-jerantinine A and (-)-melodinine P and derivatives is reported, showing potent activity against MDA-MB-231 triple-negative breast cancer cells. Furthermore, metabolomics and live cell reporter assays reveal that (-)-jerantinine A alters cellular redox metabolism and induces oxidative stress, resulting in cell cycle arrest.
RSC MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Christopher J. Smedley
Summary: This article describes a novel method for synthesizing two unique sulfonyl fluoride cores using the highly reactive SASF center in addition reactions with DMSO and DMF. The stereoselectivity and excellent yields of the reactions are demonstrated.
CHEMICAL COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Samuel G. Nonis, Joel Haywood, Jason W. Schmidberger, Emily R. R. Mackie, Tatiana P. Soares da Costa, Charles S. Bond, Joshua S. Mylne
Summary: The discovery of a posttranslational modification responsible for creating concanavalin A involved an unprecedented rearrangement in amino-acid sequence. Asparaginyl endopeptidase (AEP) was found to play a role in this process, with structural analysis revealing its capability of carrying out the necessary reactions. Biophysical assays showed that pro-conA is less stable than conA, with implications for tetramerization in solution.