Article
Chemistry, Organic
Anding Li, Ziru He, Bingyan Liu, Zhen Yang, Zichun Zhang
Summary: In this study, a concise and stereoselective total synthesis of (+/-)-cephanolide B was accomplished in 15 steps. The key steps in the synthesis included an intermolecular Diels-Alder reaction, a tandem reaction featuring intramolecular Pauson-Khand reaction, 6 pi-electrocyclization, and oxidative aromatization to construct the ABC-tricyclic rings (6-5-6), as well as a phthaloyl peroxide-mediated arene oxygenation to install the C-13 phenol group.
Article
Chemistry, Multidisciplinary
Deevi Basavaiah, Gangadhararao Golime, Shivalal Banoth, Saidulu Todeti
Summary: This study presents the first example of an umpolung strategy for intermolecular [2 + 2 + 1] cycloaddition between two aryl aldehydes and a nitrile, resulting in the formation of N-C, O-C, and C-C bonds and providing a straightforward synthetic protocol for obtaining 2,4,5-trisubstituted oxazoles.
Article
Chemistry, Multidisciplinary
Hui Wang, Yi Liu, Hongyuan Zhang, Baochao Yang, Haibing He, Shuanhu Gao
Summary: The asymmetric total syntheses of cephalotaxus C19 diterpenoids, which possess a unique cycloheptene A ring with a chiralmethyl group at C-12, were achieved using a universal strategy. Six members, including previously unreported compounds, were successfully synthesized. The concise approach involved a Nicholas/Hosomi-Sakurai cascade reaction to generate the cycloheptene ring with a chiral methyl group, followed by an intramolecular Pauson-Khand reaction for the construction of the target molecules' complete skeleton. This work provides a new strategy for the synthetic analysis of cephalotaxus diterpenoids and structurally related natural products.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2023)
Review
Chemistry, Multidisciplinary
Zhen Yang
Summary: The total synthesis endeavors contribute to the discovery and invention of new synthetic reactions to advance organic synthesis. Bioactive compounds share common features, such as molecular complexity, protein-binding ability, structural rigidity, and three-dimensionality. Total synthesis offers an alternative solution for generating scarce natural products and their derivatives for studying their biological functions.
ACCOUNTS OF CHEMICAL RESEARCH
(2021)
Article
Chemistry, Multidisciplinary
Ridge Michael P. Ylagan, Eric Jaewon Lee, Daniela E. Negru, Paolo Ricci, Bohyun Park, Haram Ryu, Mu-Hyun Baik, P. Andrew Evans
Summary: We report an enantioselective rhodium(I)-catalyzed Pauson-Khand reaction using 1,6-chloroenynes that contain challenging 1,1-disubstituted olefins. Unlike previous studies, this new approach allows for a wider range of substrates, including both carbon and heteroatom tethers with polar and non-polar substituents on the alkene. DFT calculations reveal the critical role of the halide, which pre-polarizes the alkyne and provides the appropriate steric profile for a favorable interaction with the chiral diphosphine ligand.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Lisa-Catherine Rosenbaum, Maximilian Haefner, Tanja Gaich
Summary: A racemic and scalable enantioselective total synthesis of (+)-waihoensene was achieved, featuring an angular triquinane substructure with an all-cis-fused tetracyclic backbone and six contiguous stereocenters, four of which are quaternary. Enantioselectivity was introduced at an early stage, and key structural features were efficiently installed through several diastereoselective reactions.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Organic
Paul Shaw, Storm J. Hassell-Hart, Gayle E. Douglas, Andrew G. Malcolm, Alan R. Kennedy, Gemma White, Laura C. Paterson, William J. Kerr
Summary: In this study, we applied silyl enol ether moieties as efficient alkene coupling partners within cobalt-mediated intramolecular Pauson-Khand reactions. This cyclization strategy delivers valuable oxygenated cyclopentenone products in high yields and allows for the incorporation of a variety of decorated structures.
Article
Chemistry, Applied
Magesh Sampath, Sembian Ruso Jayaraman, Vishnuvardhan Reddy Eda, Rajendar Potham, Rajeev Rehani Budhdev, Saikat Sen, Rakeshwar Bandichhor, Srinivas Oruganti
Summary: An efficient and elegant enantioselective synthesis of the key chiral pyrrolidine fragment for Upadacitinib (ABT-494) was described using Oppolzer's chiral sultam-directed asymmetric 1,3 dipolar cycloaddition. The method provided the desired level of diastereoselectivity and enantioselectivity in the construction of the 3,4-syn substituted pyrrolidine moiety.
ORGANIC PROCESS RESEARCH & DEVELOPMENT
(2022)
Review
Chemistry, Organic
Pritha Mandal
Summary: Click reactions have become popular among chemists due to their ambient reaction parameters and wide application in various research fields. Photoinitiated click reactions provide additional spatial and temporal control, ensuring productive bioorthogonal reactions. This review discusses various types of 1,3-dipolar cycloaddition reactions and their applications in protein bioconjugation.
CURRENT ORGANIC CHEMISTRY
(2023)
Review
Chemistry, Organic
Sambasivarao Kotha, Ambareen Fatma
Summary: This article highlights various synthetic methodologies related to tetraquinane frameworks in crinipellin derivatives, including different synthetic strategies and emphasis on the core structure research.
ASIAN JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Organic
Jian-Bin Lu, Shu-Yuan Liang, Wu-Tao Gui, Zhi-Chao Chen, Wei Du, Ying-Chun Chen
Summary: A relay catalytic protocol utilizing pyrrolidine and palladium catalysis has been developed for the asymmetric synthesis of 1,3-diamine derivatives from 3-substituted 1,3-dienes, sulfuric diamide, and aldehydes. This one-pot, three-component reaction offers the advantages of high atom step economy and operational simplicity, providing an efficient and straightforward access to valuable 1,3-diamines containing quaternary and tertiary stereogenic centers with moderate to good enantioselectivity.
Article
Chemistry, Organic
Jorge Escorihuela
Summary: In this study, density functional theory calculations are used to clarify the mechanism and reactivity of enynes containing a vinyl fluoride moiety for the Co2(CO)(8)-mediated intramolecular Pauson-Khand reaction. The results show that alkene insertion is the rate-determining step for this reaction. The effect of substituents on the reaction has also been investigated, with fluorinated enynes having lower reactivity compared to malonate homologues.
SYNTHESIS-STUTTGART
(2023)
Article
Chemistry, Organic
Jisna Jose, Thomas Mathew
Summary: 2-Cyclopentenone and its derivatives are highly esteemed synthetic intermediates with exceptional utility in organic synthesis. They are favored structural motifs in numerous pharmaceutical drugs and natural products, highlighting their significance. The review discusses the various methods used to synthesize cyclopentenones from 2016 to 2023.
Article
Chemistry, Applied
Kai-Kai Wang, Yan-Li Li, Rong-Xiang Chen, Ai-Li Sun, Zhan-Yong Wang, Ying-Chao Zhao, Ming-Yue Wang, Shi Sheng
Summary: The additive-free 1,3-dipolar cycloaddition reaction enables diversity-oriented synthesis of novel and structurally complex derivatives in high yields and excellent diastereoselectivities.
ADVANCED SYNTHESIS & CATALYSIS
(2022)
Article
Chemistry, Organic
Li Jing, Zhong-Jun Li, Er-Qing Li
Summary: We have developed a new 1,3-bis-electrophilic motif and applied it in palladium-catalyzed (3 + 2) annulations. This method offers a straightforward approach to constructing functionalized pyrrolidines with good yields. Importantly, the configuration (Z/E) of the 1,3-bis-electrophilic motif does not affect the yield and chemoselectivity of the reaction. Furthermore, preliminary asymmetric investigations using Pd(0)/thiourea synergistic catalysis resulted in moderate enantioselectivity.
ORGANIC CHEMISTRY FRONTIERS
(2023)
Article
Chemistry, Medicinal
Fredrik Edfeldt, Johan Evenas, Matti Lepisto, Alison Ward, Jens Petersen, Lisa Wissler, Mattias Rohman, Ulf Sivars, Karin Svensson, Matthew Perry, Isabella Feierberg, Xiao-Hong Zhou, Thomas Hansson, Frank Narjes
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2015)
Article
Chemistry, Medicinal
Roine I. Olsson, Yafeng Xue, Stefan von Berg, Anna Aagaard, Jane McPheat, Eva L. Hansson, Jenny Bernstrom, Pia Hansson, Johan Jirholt, Hanna Grindebacke, Agnes Leffler, Rongfeng Chen, Yao Xiong, Hongbin Ge, Thomas G. Hansson, Frank Narjes
Article
Chemistry, Medicinal
Johan Evenas, Fredrik Edfeldt, Matti Lepisto, Naila Svitacheva, Anna Synnergren, Britta Lundquist, Mia Granse, Anna Ronnholm, Mikael Varga, John Wright, Min Wei, Sherrie Yue, Junfeng Wang, Chong Li, Xuan Li, Gang Chen, Yong Liao, Gang Lv, Ann Tjornebo, Frank Narjes
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2014)
Article
Pharmacology & Pharmacy
Simona Cianetti, Vincent Brett Cooper, Barbara Attenni, Vincenzo Pucci, Fabrizio Fiore, Claudio Giuliano, Ralph Laufer, Cristina Gardelli, Edith Monteagudo, Frank Narjes, Gareth Edward Pearce, Michael Rowley
Article
Chemistry, Medicinal
Frank Narjes, Benedetta Crescenzi, Marco Ferrara, Jorg Habermann, Stefania Colarusso, Maria del Rosario Rico Ferreira, Ian Stansfield, Angela Claire Mackay, Immacolata Conte, Caterina Ercolani, Simone Zaramella, Maria-Cecilia Palumbi, Philip Meuleman, Geert Leroux-Roels, Claudio Giuliano, Fabrizio Fiore, Stefania Di Marco, Paola Baiocco, Uwe Koch, Giovanni Migliaccio, Sergio Altamura, Ralph Laufer, Raffaele De Francesco, Michael Rowley
JOURNAL OF MEDICINAL CHEMISTRY
(2011)
Article
Chemistry, Medicinal
Frank Narjes, Yafeng Xue, Stefan von Berg, Jesper Malmberg, Antonio Llinas, Rome Olsson, Johan Jirholt, Hanna Grindebacke, Agnes Leffler, Nafizal Hossain, Matti Lepisto, Linda Thunberg, Hanna Leek, Anna Aagaard, Jane McPheat, Eva L. Hansson, Elisabeth Back, Stefan Tangefjord, Rongfeng Chen, Yao Xiong, Ge Hongbin, Thomas G. Hansson
JOURNAL OF MEDICINAL CHEMISTRY
(2018)
Article
Chemistry, Organic
Stefania Colarusso, Immacolata Conte, Marcello Di Filippo, Caterina Ercolani, Angela C. Mackay, Maria Cecilia Palumbi, Maria del Rosario Rico Ferreira, Ian Stansfield, Simone Zaramella, Frank Narjes, Joerg Habermann
Article
Chemistry, Organic
Robert K. Boeckman, Maria Rico del Rosario Ferreira, Lorna H. Mitchell, Pengcheng Shao, Michael J. Neeb, Yue Fang
Article
Chemistry, Medicinal
Igor Shamovsky, Lena Ripa, Frank Narjes, Britta Bonn, Stefan Schiesser, Ina Terstiege, Christian Tyrchan
Summary: This study investigates the mechanism of N-hydroxylation of aromatic and heteroaromatic amines by CYP1A2 using density functional theory calculations, finding that bioactivation follows an anionic pathway. The results demonstrate that mutagenicity of ArNH2 can be removed by disrupting geometric and electrostatic fit to CYP1A2.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Frank Narjes, Antonio Llinas, Stefan von Berg, Johan Jirholt, Sarah Lever, Rikard Pehrson, Mia Collins, Anna Malmberg, Petter Svanberg, Yafeng Xue, Roine Olsson, Jesper Malmberg, Glyn Hughes, Nafizal Hossain, Hanna Grindebacke, Agnes Leffler, Nina Krutrok, Elisabeth Back, Marie Ramnegard, Matti Lepisto, Linda Thunberg, Anna Aagaard, Jane McPheat, Eva L. Hansson, Rongfeng Chen, Yao Xiong, Thomas G. Hansson
Summary: A novel series of isoindoline-based inverse agonists of the nuclear receptor RORC2, including compound 20, showed potent inhibition of IL-17A secretion and good metabolic stability in preclinical studies. Compound 20 reduced thymocyte numbers and IL-17A containing gamma delta-T cells, and progressed to phase 1 clinical studies based on favorable safety profile.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Medicinal
Hongtao Zhao, Frank Narjes
Summary: The kinetics of PROTAC-induced protein degradation were modelled using the equilibrium approximation, and the equations derived from the modelling revealed the dependency of the half-maximal degradation concentration (DC50) on the dissociation constant of the ternary complex, the expression level of the E3 ligase, and the effective ubiquitylation rate. These predicted relationships were rigorously confirmed by experimental evidence.
Article
Chemistry, Multidisciplinary
Jessica Iegre, Sona Krajcovicova, Anders Gunnarsson, Lisa Wissler, Helena Kaeck, Anna Luchniak, Stefan Tangefjord, Frank Narjes, David R. Spring
Summary: The study presents a two-component peptide stapling strategy to inhibit the protein-protein interaction between Nrf2 and Keap1. The most promising peptide, P8-H, binds to Keap1 with nanomolar affinity and effectively induces gene transcription in specific cells at sub-micromolar concentration. This strategy provides a new approach to develop cell-permeable peptide-based inhibitors.
Review
Biochemistry & Molecular Biology
Eric Valeur, Frank Narjes, Christian Ottmann, Alleyn T. Plowright
Article
Chemistry, Medicinal
Shibin Zhao, Julian Maceren, Mia Chung, Samantha Stone, Raphael Geiben, Melissa L. Boby, Bradley S. Sherborne, Derek S. Tan
Summary: Antibiotic resistance is a major threat to public health, with Gram-negative bacteria presenting unique challenges due to their low permeability and efflux pumps. Limited understanding of the chemical rules for overcoming these barriers hinders antibacterial drug discovery. Efforts to address this issue, such as screening compound libraries and using cheminformatic analysis, have led to the design of sulfamidoadenosines with diverse substituents, showing potential utility in accumulation in Escherichia coli.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Jichun Li, Qing Li, Shuai Xia, Jiahuang Tu, Longbo Zheng, Qian Wang, Shibo Jiang, Chao Wang
Summary: This study successfully developed a short peptide mimetic as a MERS-CoV fusion inhibitor by reproducing the key recognition features of the HR2 helix. The resulting 23-mer lipopeptide showed comparable inhibitory effect to the 36-mer HR2 peptide HR2P-M2. This has important implications for developing short peptide-based antiviral agents to treat MERS-CoV infection.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Krista Jaunsleine, Linda Supe, Jana Spura, Sten van Beek, Anna Sandstrom, Jessica Olsen, Carina Halleskog, Tore Bengtsson, Ilga Mutule, Benjamin Pelcman
Summary: Beta(2)-adrenergic receptor agonists can stimulate glucose uptake by skeletal muscle cells and are therefore potential treatments for type 2 diabetes. The chirality of compounds has a significant impact on the activity of these agonists. This study found that certain synthesized compounds showed higher glucose uptake activity. These findings provide important information for the design of novel beta(2)AR agonists for T2D treatment.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Xin Xu, Jia Chen, Guan Wang, Xiaojuan Zhang, Qiang Li, Xiaobo Zhou, Fengying Guo, Min Li
Summary: The study focuses on EZH2, a promising therapeutic target for various types of cancers. Researchers designed and synthesized a series of novel derivatives aiming to enhance the EZH2 inhibition activity. Among them, compound 28 displayed potent EZH2 inhibition activity and showed high anti-proliferative effects in lymphoma cell lines and xenograft mouse models. The study suggests that compound 28 has potential as a therapeutic candidate for EZH2-associated cancers.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Wei Zhang, Wei Liu, Ya-Dong Zhao, Li-Zi Xing, Ji Xu, Rui-Jun Li, Yun-Xiao Zhang
Summary: This study developed a series of aromatic amide derivatives based on Rhein and investigated their inhibitory activity against alpha-Syn aggregation. Two of these compounds showed promising potential in treating Parkinson's disease by stabilizing alpha-Syn's conformation and disassembling alpha-Syn oligomers and fibrils.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
Article
Chemistry, Medicinal
Mani Sharma, S. S. S. S. Sudha Ambadipudi, Neeraj Kumar Chouhan, V. Lakshma Nayak, Srihari Pabbaraja, Sai Balaji Andugulapati, Ramakrishna Sistla
Summary: Therapeutically active lipids in drug delivery systems can enhance the safety and efficacy of treatment. The liposome formulation created using synthesized biologically active lipids showed additive anti-cancer effects and reduced tumorigenic potential.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2024)
