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)
Review
Chemistry, Inorganic & Nuclear
Konrad Kowalski
Summary: Cancer is a leading cause of death worldwide. This review emphasizes the significance of metal-catalyzed azide-alkyne cycloaddition reactions in synthesizing ferrocenyl-x-1,2,3-triazolyl-R compounds with anticancer activity. The review discusses over 160 ferrocenyl-triazoles and their classification into four categories based on their chemical properties. The study demonstrates that copper-catalyzed azide-alkyne cycloaddition reactions are particularly important in yielding the highest number of ferrocenyl-x-1,2,3-triazolyl compounds with anticancer activity. Oxidative stress and reactive oxygen species generation are identified as common mechanisms through which the ferrocenyl moiety contributes to the anticancer activity of 1,2,3-triazolyl derivatives. The review contains 23 figures, 24 schemes, and 208 references.(c) 2022 Elsevier B.V. All rights reserved.
COORDINATION CHEMISTRY REVIEWS
(2023)
Article
Chemistry, Multidisciplinary
En-Chih Liu, Joseph J. Topczewski
Summary: This study reported the first enantioselective triazole synthesis using nickel-catalyzed alkyne-azide cycloaddition (NiAAC). The mechanism involves a spontaneous [3,3]-sigmatropic rearrangement of the allylic azide, resulting in 1,4,5-trisubstituted triazole products complementary to those obtained by CuAAC. Initial mechanistic experiments suggest that the NiAAC reaction proceeds through a monometallic Ni complex, distinct from the CuAAC mechanism.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Chemistry, Multidisciplinary
Chung-Sung Lee, Jiabing Fan, Hee Sook Hwang, Soyon Kim, Chen Chen, Minjee Kang, Tara Aghaloo, Aaron W. James, Min Lee
Summary: Extracellular vesicles, particularly exosome mimetics (EMs) with hydroxyapatite-binding moieties, have demonstrated potential as biocarriers for targeted bone regeneration. The introduction of a Smoothened agonist (SAG) greatly enhanced the osteogenic capacity of the EMs through hedgehog signaling activation. The integration of EM/SAG into a scaffold significantly improved in vivo reossification, and biodistribution studies confirmed the accumulation of systemically administered EMs in bone tissue.
Article
Chemistry, Organic
Ajaz Ahmed, Debaraj Mukherjee
Summary: This article presents a method for the stereoselective synthesis of orthogonally protected N-substituted beta-aminooxysugars from sugar epoxides and nitrones derived from aromatic aldehydes. Both ether- and ester-protected sugar epoxides can be used in the synthesis. The synthesized aminooxy sugars can react with aldehydes bearing or free reducing sugars under heating conditions to yield N-O-linked 1,1-/1,5/1,6-disaccharide mimetics in good yield.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Joyce C. Oliveira, Renato L. de Carvalho, Hugo G. S. Sampaio, Joao Honorato, Javier A. Ellena, Felipe T. Martins, Joao V. M. Pereira, Pedro M. S. Costa, Claudia Pessoa, Rafaela S. Ferreira, Maria H. Araujo, Claus Jacob, Eufranio N. da Silva Junior
Summary: Our research group successfully combined two redox centres (ortho-quinone/para-quinone or quinone/selenium-containing triazole) through a copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction, leading to significant anticancer activity. We synthesized 15 new quinone-based derivatives and evaluated their efficacy in nine cancer cell lines and the fibroblast line L929. Our study confirmed the effectiveness of A-ring functionalized para-quinones coupled with ortho-quinones in obtaining diverse two redox centre compounds with potential applications against cancer.
Review
Chemistry, Medicinal
Anna Pasieka, Eleonora Diamanti, Elisa Uliassi, Maria Laura Bolognesi
Summary: Click chemistry and targeted protein degradation, two flourishing trends in medicinal chemistry. Can they be a winning combination? In this review, we provide the reader with selected examples offered by the combination of these two approaches trying to find a response to this question.
Article
Chemistry, Physical
Zita G. Rios-Malvaez, Ma-Angeles Cano-Herrera, Juan Carlos Davila-Becerril, Gustavo Mondragon-Solorzano, Maria Teresa Ramirez-Apan, David Morales-Morales, Joaquin Barroso-Flores, Jonnathan G. Santillan-Benitez, M. V. Basavanag Unnamatla, Marco Antonio Garcia-Eleno, Nelly Gonzalez-Rivas, Erick Cuevas-Yanez
Summary: A novel series of 4-(1,2,3-triazol-1-yl) salicylic acid derivatives were synthesized and their selective activity against various tumoral cell lines was explored in vitro. Molecular docking studies suggested a strong interaction between some compounds and ARG-154 in STAT3.
JOURNAL OF MOLECULAR STRUCTURE
(2021)
Article
Chemistry, Organic
Avetik G. Gevondian, Yury N. Kotovshchikov, Gennadij Latyshev, Nikolay Lukashev, Irina P. Beletskaya
Summary: A straightforward domino approach has been developed for the assembly of benzoxazole-derived sulfonamides, based on the in situ generation of diazo compounds from readily available starting material followed by denitrogenative transformation. The method is operationally simple, with a broad substrate scope and generally good yields, providing a library of target compounds.
JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Hendrik Hessefort, Angelina Gross, Simone Seeleithner, Markus Hessefort, Tanja Kirsch, Lukas Perkams, Klaus Ole Bundgaard, Karen Gottwald, David Rau, Christopher Guenther Franz Graf, Elisabeth Rozanski, Sascha Weidler, Carlo Unverzagt
Summary: The in-vivo activity of EPO is carbohydrate-dependent, with the number of sialic acid residues regulating its circulatory half-life. A chemoenzymatic approach was developed for obtaining glycoforms of EPO with and without sialic acids. Synthetic EPOs showed biological recognition by forming 1:1 complexes with recombinant EPO receptor.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Biochemical Research Methods
Christine Sternstein, Theresa-Maria Boehm, Julian Fink, Jessica Meyr, Martin Luedemann, Melanie Krug, Kirill Kriukov, Cenk O. Gurdap, Erdinc Sezgin, Regina Ebert, Juergen Seibel
Summary: The glycosylation of cellular membranes is essential for cell survival and communication. A functionalized lipid anchor called FLAME was designed for introducing into cellular membranes. FLAME was successfully incorporated into the membranes of human mesenchymal stromal cells (hMSC) as a temporary and non-toxic marker. It can be used to study the partitioning behavior in different phases and analyze diffusion behavior in model and cell membranes using fluorescence correlation spectroscopy (FCS).
BIOCONJUGATE CHEMISTRY
(2023)
Article
Chemistry, Organic
Zoeisha S. Chinoy, Kelley W. Moremen, Frederic Friscourt
Summary: This study reports a new chemical tool, sydnone-aglycon, that can be used for the synthesis of O-glycans and the high-throughput screening of O-glycan-lectin interactions.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Carla Gomes, Mariana Costa, Susana M. M. Lopes, Bernardo Albuquerque Nogueira, Rui Fausto, Jose A. Paixao, Teresa M. V. D. e Melo, Luisa M. D. R. S. Martins, Marta Pineiro
Summary: The development of sustainable processes requires the integration of green chemistry principles. In this study, a solvent-free synthesis method was developed to prepare new copper catalysts, which efficiently catalyze cycloaddition reactions under solvent-free mechanochemical conditions. Through this process, the principles of atom economy, reduction of solvents and auxiliaries, design for energy efficiency, and reduction of derivatives and catalysis are combined.
NEW JOURNAL OF CHEMISTRY
(2024)
Article
Chemistry, Organic
Sumit K. Singh, Sunil Kumar, Mangal S. Yadav, Subrato Bhattacharya, Vinod K. Tiwari
Summary: This report describes a convenient Cu(I)-catalyzed tandem synthesis method for the efficient synthesis of dihydrophenanthridinediones and substituted isoquinolinones using glycosyl 1,2,3-triazole-based pyridinamide ligands. The method successfully forms biologically relevant heterocyclic scaffolds in high yields through intermolecular C-C cross-coupling followed by intramolecular cyclization. Notable features of this method include low catalytic loading, use of cost-effective and biocompatible ligands, high reaction yield, and easily accessible starting materials, making it a versatile protocol.
SYNTHESIS-STUTTGART
(2023)
Article
Chemistry, Multidisciplinary
Ali Reza Sardarian, Fatemeh Abbasi, Mohsen Esmaeilpour
Summary: In this paper, Fe3O4@Zein-Cu(II) NPs were synthesized and used as a reusable magnetic catalyst for Cu-catalyzed azide-alkyne cycloaddition reactions. The catalyst showed excellent catalytic activity and selectivity in the regioselective click preparation of fluorescent 1,4-disubstituted-1,2,3-triazoles. It exhibited good magnetism, allowing easy recovery and reuse for multiple runs without significant loss in activity.
SUSTAINABLE CHEMISTRY AND PHARMACY
(2023)
Article
Chemistry, Organic
Andrew D. W. Earl, Freda F. F. Li, Chao Ma, Daniel P. P. Furkert, Margaret A. A. Brimble
Summary: This research describes a facile and efficient synthesis of the [7,6]-spirocyclic core of 13-desmethyl spirolide C, a marine natural product with remarkable bioactivity against biomarkers of Alzheimer's Disease. The synthesis involves an aza-Claisen rearrangement and a highly exo-selective Diels-Alder cycloaddition. This strategy not only provides a more efficient access to the spirocyclic core for the total synthesis of 13-desmethyl spirolide C, but also allows for convenient preparations of analogues for biological evaluation.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2023)
Article
Pharmacology & Pharmacy
Johanes K. Kasim, Jiwon Hong, Anthony J. R. Hickey, Anthony R. J. Phillips, John A. Windsor, Paul W. R. Harris, Margaret A. Brimble, Iman Kavianinia
Summary: Pancreatic ductal adenocarcinoma is a debilitating disease with no effective treatments. Trichoderin A, a natural product, shows promise as an anticancer agent. It selectively kills pancreatic cancer cells under glucose deprivation, which is significant given the nutrient-deprived nature of the disease.
Article
Chemistry, Medicinal
Tyla I. Alexander, Zoe Tasma, Andrew Siow, Tayla A. Rees, Margaret A. Brimble, Paul W. R. Harris, Debbie L. Hay, Christopher S. Walker
Summary: The peptides PACAP and VIP, along with their corresponding receptors, have potential as drug targets for neurological and pain-related disorders. This study developed fluorescently labeled analogues of these peptides to study receptor regulation through processes such as internalization. The labeled peptides were found to be functional at their receptors and underwent time-dependent internalization.
ACS PHARMACOLOGY & TRANSLATIONAL SCIENCE
(2023)
Article
Chemistry, Organic
Xin Qiu, Daniel Chong, Antony J. Fairbanks
Summary: Unprotected sugars can be selectively acetylated in aqueous solution by stirring with acetic anhydride and a weak base, such as sodium carbonate. This reaction specifically targets the anomeric hydroxyl group of mannose, 2-acetamido, and 2-deoxy sugars and can be conducted on a large scale. However, over-reaction and the formation of product mixtures can occur due to competitive intramolecular migration of the 1-O-acetate to the 2-hydroxyl group when these two substituents are in cis configuration.
Article
Nanoscience & Nanotechnology
Patrick Cahill, Thomas M. Grant, David Rennison, Olivier Champeau, Michael Boundy, Emillie Passfield, Mattias Berglin, Margaret A. Brimble, Johan Svenson
Summary: This study describes the development of environmentally friendly antifouling biocides based on a cyclic dipeptide scaffold. The lead compound (1) was synthesized and tested for its compatibility with a coating, efficacy against biofouling, and biodegradation. The results showed stable leaching rates under dynamic conditions but low or no leaching under static conditions. When deployed in the ocean, the coating demonstrated measurable reductions in biofouling for up to 11 weeks. Biodegradation of the compound in seawater was also evaluated. These findings provide valuable insights for the future development of commercial antifouling products.
ACS APPLIED BIO MATERIALS
(2023)
Article
Biochemistry & Molecular Biology
Elena Harjes, Patrick J. B. Edwards, Sean W. W. Bisset, Mark L. L. Patchett, Geoffrey B. B. Jameson, Sung-Hyun Yang, Claudio D. D. Navo, Paul W. R. Harris, Margaret A. A. Brimble, Gillian E. E. Norris
Summary: Glycocin F (GccF), secreted by Lactobacillus plantarum KW30, inhibits susceptible bacteria growth at nanomolar concentrations. A small chemical modification of Ser18, substituting the C-alpha proton with a methyl group, significantly reduces the antimicrobial activity of GccF. The comparison of the NMR structures of GccF(alpha-methylSer18) and native GccF reveals differences in loop conformation, dynamics, and glycan presentation, suggesting their importance in the interaction of GccF with essential physiological target molecules.
Article
Virology
Alice-Roza Eruera, Alice M. McSweeney, Geena M. McKenzie-Goldsmith, Helen K. Opel-Reading, Simone X. Thomas, Ashley C. Campbell, Louise Stubbing, Andrew Siow, Jonathan G. Hubert, Margaret A. Brimble, Vernon K. Ward, Kurt L. Krause
Summary: Norovirus is a major cause of viral gastroenteritis worldwide. This study provides new insights for drug design against GII.4 genogroup of noroviruses.
Article
Chemistry, Organic
C. H. Andy Wong, Jonathan G. Hubert, Kevin J. Sparrow, Lawrence D. Harris, Peter C. Tyler, Margaret A. Brimble
Summary: This study presents a one-pot method for synthesizing similar fleximers using a bifunctional copper catalyst, which can generate aryl azides in situ and react with terminal alkynes to form triazoles.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2023)
Article
Chemistry, Organic
Xiao-Bo Ding, Alexander Wung, Daniel P. Furkert, Margaret A. Brimble
Summary: We report a facile synthesis of the spirocyclic core of portimines A and B, two natural products with remarkable anticancer, anti-HIV, and antifouling activities. Our strategy involves a scalable Diels-Alder addition and a diastereoselective lactonization, enabling differentiation of the carbonyl groups. This approach overcame issues encountered in previous studies and provided a useful intermediate for the synthesis of portimines.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2023)
Review
Chemistry, Multidisciplinary
Shengping Zhang, Luis De Leon M. Rodriguez, Freda F. F. Li, Margaret A. Brimble
Summary: Selective modification of peptides and proteins at tyrosine residues has gained significant attention in recent years. This review provides a comprehensive summary of the latest advancements in tyrosine-selective cleavage, functionalization, and conjugation, complementing the existing body of work on site-specific modification of peptides and proteins. This research holds great relevance across various disciplines, including chemical, biological, medical, and material sciences.
Review
Biochemistry & Molecular Biology
Louise A. A. Stubbing, Jonathan G. G. Hubert, Joseph Bell-Tyrer, Yann O. O. Hermant, Sung Hyun Yang, Alice M. M. McSweeney, Geena M. M. McKenzie-Goldsmith, Vernon K. K. Ward, Daniel P. P. Furkert, Margaret A. A. Brimble
Summary: Viral infections are a major cause of acute morbidity in humans, and efforts have been made to develop drugs to treat associated diseases. Peptide-based enzyme inhibitors, short sequences of three or four residues, are being developed to enhance their activity and pharmaceutical properties. This review focuses on the design of inhibitors targeting highly conserved viral proteases 3C/3CL(pro), which play a key role in viral replication and have minimal similarity with mammalian proteases. The development of P-1 glutamine isosteres to generate potent inhibitors mimicking the natural substrate sequence is highlighted.
RSC CHEMICAL BIOLOGY
(2023)
Article
Chemistry, Organic
Dennise Palpal-latoc, Margaret A. Brimble, Paul W. R. Harris, Aimee J. Horsfall
Summary: Macrocyclic depsipeptides, a class of bioactive natural products, have gained increasing attention due to their antimicrobial activity. However, the low yields in peptide ester (depsipeptide) bond formation have hindered the access to these structures for further studies. In this study, we systematically investigated the factors influencing on-resin depsipeptide bond formation using simplified sequences derived from antibiotic peptides. Our findings highlight the importance of reaction solvent and the number of amino acids in improving the acylation efficiency. The impact of protecting groups and stereochemistry was also evaluated, while the addition of surfactants and 6-ClHOBt showed little effect, and no significant difference was observed between different resins.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2023)
Review
Chemistry, Organic
Marzieh Ahangarpour, Iman Kavianinia, Margaret A. Brimble
Summary: Over the last few decades, synthetic organic chemists have been focusing on the design and discovery of chemical reactions that enable the modification of proteins at specific sites. The selective functionalization of peptides and proteins offers an exciting opportunity for creating valuable multicomponent conjugates with diverse applications. Various strategies, including the thia-Michael click addition reaction, have been developed for the selective modification of cysteine-containing proteins. This review summarizes the different reactions for cysteine-selective peptide and protein modification, with a specific focus on the thia-Michael click addition reaction and its applications.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2023)
Article
Food Science & Technology
Bin Lin, Smitha Nair, Daniel M. J. Fellner, Noha Ahmed Nasef, Harjinder Singh, Leonardo Negron, David C. Goldstone, Margaret A. Brimble, Juliet A. Gerrard, Laura Domigan, Jackie C. Evans, Jonathan M. Stephens, Troy L. Merry, Kerry M. Loomes
Summary: 3,6,7-trimethyllumazine (Lepteridine (TM)) is a newly discovered natural pteridine derivative found in Manuka honey, which inhibits gelatinase activity by interfering with the connection between MMP-9 and the gelatin matrix.
Article
Chemistry, Organic
Clouie Justin Aguilar, Makhdoom Sarwar, Sujay Prabakar, Wenkai Zhang, Paul W. R. Harris, Margaret A. Brimble, Iman Kavianinia
Summary: In this study, a photoinitiated thiol-ene click reaction was used to synthesize S-lipidated collagen model peptide amphiphiles. This approach improved the characteristics and aqueous solubility of the peptides, showing significant potential for the design and application of functional peptide amphiphiles.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2023)
