Review
Chemistry, Multidisciplinary
Yan-Long Zheng, Stephen G. Newman
Summary: This article discusses two common families of chemical reactions - cross-coupling reactions and pi bond addition reactions - and the significant overlap between them. Recent advancements in catalysis have revealed the role of compounds such as esters, aldehydes, and alcohols in nickel- and palladium-catalyzed reactions, offering promising alternatives for the preparation of amides, ketones, substituted alcohols, alkanes, and more. The focus is on the key mechanistic steps that allow these non-traditional substrates to be incorporated into cross-coupling-like catalytic cycles.
CHEMICAL COMMUNICATIONS
(2021)
Article
Chemistry, Multidisciplinary
Vincent M. Kassel, Christopher M. Hanneman, Connor P. Delaney, Scott E. Denmark
Summary: Reaction conditions have been developed for refractory heteroaryl-heteroaryl Suzuki-Miyaura cross-couplings using neopentyl heteroarylboronic esters, heteroaryl bromides and chlorides, and potassium trimethylsilanolate (TMSOK) under anhydrous conditions. The addition of trimethyl borate enhances reaction rates by several mechanisms, enabling cross-coupling of diverse reaction partners in good yields and short reaction times.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2021)
Article
Chemistry, Multidisciplinary
Alasdair K. Cooper, Megan E. Greaves, William Donohoe, Paul M. Burton, Thomas O. Ronson, Alan R. Kennedy, David J. Nelson
Summary: A nickel/dppf catalyst system successfully achieved Suzuki-Miyaura cross-coupling reactions of certain chloropyridines and chloroquinolines but not others, due to differences in the reaction mechanism. Chloropyridines rapidly undergo oxidative addition to the catalyst, while alpha-halo-N-heterocycles form catalytically inactive dimeric nickel species.
Review
Chemistry, Multidisciplinary
Reza Emadi, Abbas Bahrami Nekoo, Fatemeh Molaverdi, Zahra Khorsandi, Reza Sheibani, Hojjat Sadeghi-Aliabadi
Summary: C-N cross-coupling bond formation reactions are valuable approaches in synthesizing important chemical compounds such as anilines and their derivatives. Recent developments in this field focus on versatile catalysts, simple operation methods, and green reaction conditions. This review article provides an overview of C-N cross-coupling reactions in pharmaceutical compound synthesis reports, with selected examples of N-arylation reactions of nitrogen-based compounds and aryl halides for preparing pharmaceutical molecules.
Article
Chemistry, Multidisciplinary
Biping Xu, Weiping Su
Summary: In this paper, we report a transition metal-free, operationally simple, general method for the straightforward synthesis of 2-substituted benzoxazoles from readily available cyclohexanones and aliphatic primary amines. The key to the success of this method is the use of TEMPO as a mild oxidant, which selectively oxidizes the reaction intermediates through its multiple reactivity modes, allowing the individual steps to proceed in succession. This protocol demonstrates high reliability and excellent functional-group tolerance, enabling the synthesis of structurally diverse products, including marketed drugs, drug candidates, and natural products that are unattainable by existing methods.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Multidisciplinary
Sanghyup Seo, Donghyeon Kim, Hyunwoo Kim
Summary: The reductive cross-coupling of terminal alkenes and N-heterocyclic bromides was successfully demonstrated through ligand optimization of Pd and CuH catalysis. The optimized ligands for Pd and CuH catalysis, Briphos and DTB-DPPBz respectively, were further applied to gram-scale production of clathryimine B.
CHEMICAL COMMUNICATIONS
(2021)
Article
Chemistry, Organic
Cong Lu, Dong Jing, Yanling Shen, Jiajing Luo, Ke Zheng
Summary: One of the most straightforward strategies for organic synthesis is a visible-light-induced direct coupling between donor and acceptor substrates of a productive EDA complex. This paper presents the results of using EDA complexes of in situ formed enolates with redox-active esters for radical-coupling reactions under mild conditions. The success of sunlight-driven transformation and gram-level synthesis via flow chemistry suggests potential applications in industry.
ORGANIC CHEMISTRY FRONTIERS
(2022)
Review
Chemistry, Physical
Tong-De Tan, Ze-Shu Wang, Peng-Cheng Qian, Long-Wu Ye
Summary: Ynamides, as electron-rich heteroatom-substituted alkynes, have proven to be versatile reagents for organic synthesis and have received extensive attention. Radical reactions of ynamides, categorized by radical attack at the alpha-position and beta-position, are reviewed in this article to highlight reaction selectivity, scope, mechanism, and applicability. The aim is to provide a comprehensive summarization of these advances to guide the further development of ynamide chemistry.
Review
Chemistry, Physical
Takahide Fukuyama, Baptiste Picard, Ilhyong Ryu
Summary: This paper summarizes our team's efforts over the past two decades in the development of new catalytic methods for C-C bond formation. The versatile applications of the commercially available catalyst RuHCl(CO)(PPh3)(3) (or RuH for short) are highlighted through eight different transformations. The fundamental steps involved in the catalysis are emphasized, demonstrating how our mechanistic understanding and the diverse catalytic capabilities of RuH can be utilized to design desired catalytic cycles and develop new cross-coupling reactions with high atom-economy.
CATALYSIS SCIENCE & TECHNOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Robert D. Riley, Blake S. N. Huchenski, Karlee L. Bamford, Alexander W. H. Speed
Summary: This study demonstrates that diazaphospholene hydrides can be regenerated by the combination of phenylsilane and alkali metal salts, enabling catalytic radical reactions of aryl iodides. The method is not only applicable to aryl iodides, but can also be extended to aryl bromides, which benefit from visible light irradiation. Additionally, intermolecular radical hydroarylation reactions with arenes, thiophenes, and a pyridine have been successfully achieved.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Multidisciplinary
Igor Zayakin, Evgeny Tretyakov, Anna Akyeva, Mikhail Syroeshkin, Julia Burykina, Andrey Dmitrenok, Alexander Korlyukov, Darina Nasyrova, Irina Bagryanskaya, Dmitri Stass, Valentine Ananikov
Summary: Nitronyl nitroxides are important functional building blocks that can be used for molecular-level optimization and nano-scale device development. Efficient synthetic approaches for these compounds are still challenging.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Chemistry, Organic
Fang Wang, Qianting Zhou, Xinying Zhang, Xuesen Fan
Summary: A novel and efficient alpha-C(sp(3))-H alkenylation of cyclic amines with maleimides was presented, featuring readily available and structurally diverse substrates, a green and economical catalyst, a unique reaction pathway, mild reaction conditions, high efficiency, and excellent atom economy. This new reaction enriches the application of Fe(III)-catalyzed C(sp(3))-H activation and functionalization.
JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Chemistry, Organic
Jacob C. Hood, Yannick Tshikaya, Aaren R. Manz, Marcus C. LaPorte, Douglas A. Klumpp
Summary: In this study, a series of conjugate addition reactions were successfully performed using vinyl-substituted N-heterocycles in acid-catalyzed conversions, resulting in the formation of pyridyl and related heterocyclic products. The nucleophiles used in these reactions include 1,3-dicarbonyl compounds, cyano esters, cyano sulfone, and malonylnitrile, while the Michael accepting groups include vinyl-substituted pyridines, quinoline, and pyrazine. Double conjugate addition reactions were also achieved using 2,6-divinylpyridine and related systems.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
Review
Chemistry, Multidisciplinary
Myuto Kashihara, Yoshiaki Nakao
Summary: Cross-coupling reactions using nitroarenes as electrophiles have gained attention due to their ease of accessibility and potential advantages over haloarenes. Recent research has focused on developing new catalyst systems and reaction conditions to improve the efficiency and practicality of these reactions, with promising results in diversifying bond-forming reactions and reducing catalyst loading. Research in this field is expected to continue growing as the utility of nitroarenes in organic synthesis is reevaluated.
ACCOUNTS OF CHEMICAL RESEARCH
(2021)
Article
Chemistry, Multidisciplinary
Chao Jiang, Pinhong Chen, Guosheng Liu
Summary: In this study, a novel reaction technique combining photocatalysis and copper catalysis was developed for the radical decarboxylative C(sp(3))-C(sp(3)) cross-coupling of NHPI esters and cyclopropanols, leading to the efficient synthesis of ss-benzyl ketones. The terpyridin-4'-one ligand played a vital role in the reaction by facilitating the capture of benzylic radicals by alkyl-copper species generated through the copper-catalyzed ring-opening of cyclopropanols. The reaction exhibited broad substrate scope and wide functional group compatibility, providing a new approach for C(sp3)-C(sp3) bond formation.
SCIENCE CHINA-CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Pinku Tung, Anne Schuhmacher, Philipp E. Schilling, Jeffrey W. Bode, Neal P. Mankad
Summary: This method enables the easy preparation of various types of KATs and is compatible with a variety of functional groups, such as alkenes, esters, halides, nitriles, etc.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Multidisciplinary
Gaku Akimoto, Arianna P. Fernandes, Jeffrey W. Bode
Summary: Ubiquitylation is a process that attaches ubiquitin to proteins in eukaryotic cells and involves multiple enzymes. We have developed a method to transfer ubiquitin specifically to target proteins, which is important for studying protein function.
ACS CENTRAL SCIENCE
(2022)
Article
Multidisciplinary Sciences
Cam-Van T. Vo, Nhan V. H. Luu, Thoai T. H. Nguyen, Truc T. Nguyen, Bach Q. Ho, Thuong H. Nguyen, Thanh-Dao Tran, Quoc-Thai Nguyen
Summary: This study investigates the impact of experimental factors on the activity of pancreatic lipase in in vitro assays. It proposes optimal conditions for lipase inhibitory assays, including the use of sodium deoxycholate as an emulsifier and the tolerance of organic co-solvents. The results provide valuable information for the rational development of novel lipase inhibitors.
Article
Chemistry, Multidisciplinary
Kateryna A. Tolmachova, Jakob Farnung, Jin Rui Liang, Jacob E. Corn, Jeffrey W. Bode
Summary: A new method for generating activity-based probes for UFMylation has been developed, allowing for the selective installation of electrophilic warheads at the C-terminus of recombinant UFM1. These probes show tunable reactivity and high selectivity for proteins involved in UFMylation processes, and are active both in cell lysates and living cells.
ACS CENTRAL SCIENCE
(2022)
Article
Biochemistry & Molecular Biology
Mikail D. Levasseur, Raphael Hofmann, Thomas G. W. Edwardson, Svenja Hehn, Manutsawee Thanaburakorn, Jeffrey W. Bode, Donald Hilvert
Summary: In this study, a new enzymatic bioconjugation method was investigated to modify protein cages, allowing for diverse modification and potential fine-tuning of protein containers' properties.
Article
Chemistry, Multidisciplinary
Thua-Phong Lam, Dac-Nhan Nguyen, Tan Thanh Mai, Thanh-Dao Tran, Minh-Tri Le, Phuong Nguyen Hoai Huynh, Duc-Tuan Nguyen, Viet-Hung Tran, Dieu-Thuong Thi Trinh, Phuong Truong, Cam-Van T Vo, Khac-Minh Thai
Summary: This study explored the potential of 269 chalcones as 3CL(pro) inhibitors and identified C264 and C235 as the most potential compounds. While C264 showed higher inhibitory ability, C235 was also considered as another potential candidate.
STRUCTURAL CHEMISTRY
(2022)
Article
Plant Sciences
Cam -Van Thi Vo, Luan Cong Nguyen, Thu Thi Anh Le, Thien Ngoc Dang, Manh Quoc Dao, Thuong Hoai Nguyen, Minh Hoang Vo, Dat Van Truong, Quoc-Thai Nguyen, Phuong Thuy Viet Nguyen, Thanh-Dao Tran
Summary: Pancreatic lipase is an important target for obesity drug development. In this study, the lipase inhibitory activity of a natural flavonoid compound, C82, was evaluated through virtual screening and synthesis. C82 showed significant inhibitory activity against pancreatic lipase, suggesting its potential as an obesity drug candidate.
PHYTOCHEMISTRY LETTERS
(2022)
Correction
Multidisciplinary Sciences
Emmanuel Matabaro, Hannelore Kaspar, Paul Dahlin, Daniel L. V. Bader, Claudia E. Murar, Florian Staubli, Christopher M. Field, Jeffrey W. Bode, Markus Kunzler
SCIENTIFIC REPORTS
(2022)
Article
Chemistry, Multidisciplinary
Thomas A. Scott, Marjan Verest, Jakob Farnung, Clarissa C. Forneris, Serina L. Robinson, Xinjian Ji, Florian Hubrich, Clara Chepkirui, Daniel U. Richter, Stefanie Huber, Philipp Rust, Alena B. Streiff, Qi Zhang, Jeffrey W. Bode, Jorn Piel
Summary: Ribosomal beta-amino acid products are considered rare features in ribosomal products and can be introduced through non-canonical enzymatic splicing. A global bioinformatic analysis revealed the widespread presence of this modification in different bacterial lineages and archaea. The tested products showed potent protease inhibitory activity, highlighting their potential in drug discovery and gene-based biomolecule diversification.
Article
Chemistry, Multidisciplinary
Jakob Farnung, Kateryna A. Tolmachova, Jeffrey W. Bode
Summary: This article reports a method for preparing activity-based probes for ubiquitin and related ubiquitin-like proteins. The probes are rapidly and efficiently generated through selective acyl hydrazide modification, without requiring chromatographic purification or refolding. This method can be used to study cellular pathways involved in protein degradation and response to viral infections.
Article
Biochemistry & Molecular Biology
Kevin Neumann, Alex Vujinovic, Saidu Kamara, Andre Zwicky, Simon Baldauf, Jeffrey W. Bode
Summary: In this study, a robust and efficient chemical synthesis route was developed for accessing low-density lipoprotein receptor LA modules, using cyanopyridiniumylides (CyPY) as a masking group for carboxylic acids. The CyPY protected aspartic acids successfully suppressed aspartimide formation and were compatible with all common residues and protecting groups. This synthesis method enables new access to difficult to provide, yet promising protein domains.
RSC CHEMICAL BIOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Angus E. McMillan, Wilson W. X. Wu, Paula L. Nichols, Benedikt M. Wanner, Jeffrey W. Bode
Summary: Due to the high false positive rates in virtual screening, synthesising and validating prospective hits can be time consuming and laborious. This study evaluated large virtual libraries and identified one sub-library with unique drug-like structures. By using automated synthesis and a streamlined method of relative stereochemical assignment, the preparation of virtual screening hits was accelerated and user efficiency significantly improved.
Article
Biochemistry & Molecular Biology
Nandarapu Kumarswamyreddy, Ayami Nakagawa, Hitoshi Endo, Akie Shimotohno, Keiko U. Torii, Jeffrey W. Bode, Shunsuke Oishi
Summary: Chemical protein synthesis of plant-derived cysteine-rich secretory proteins and their late-stage derivatization has been achieved using distinct chemoselective amide bond forming reactions. The synthesized EPFs exhibit bioactivity on stomatal development and suitable fluorescent variants have been identified for subcellular localization of EPFs using comprehensive synthesis of EPF derivatives.
RSC CHEMICAL BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Nandarapu Kumarswamyreddy, Damodara N. Reddy, D. Miklos Robkis, Nao Kamiya, Ryoko Tsukamoto, Masahiro M. Kanaoka, Tetsuya Higashiyama, Shunsuke Oishi, Jeffrey W. Bode
Summary: The chemical synthesis of pollen tube attractant proteins CRPs TfLURE and TcLURE and their chimeric analogues was successfully achieved using the alpha-ketoacid-hydroxylamine (KAHA) ligation. The bioactivity of chemically synthesized TfLURE protein was comparable to the recombinant protein expressed in E. coli, as shown by in vitro assay. This convergent protein synthesis approach is efficient for preparing small protein variants.
RSC CHEMICAL BIOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Tuo Jiang, Samuele Bordi, Angus E. McMillan, Kuang-Yen Chen, Fumito Saito, Paula L. Nichols, Benedikt M. Wanner, Jeffrey W. Bode
Summary: The study introduces an instrument capable of automatically executing complex organic reactions in the laboratory, successfully implementing two desirable reaction classes in the field of organic synthesis. This system provides a convenient and safe method for future developers to conduct organic synthesis.
