Article
Chemistry, Organic
Philippe N. Bolduc, Magnus Pfaffenbach, Vanna D. Blasczak, Steven R. Mathieu, Emily A. Peterson
Summary: This article presents an efficient synthesis method for a variety of N-substituted 2-pyridones, using ethyl nitroacetate and readily available primary amine building blocks, which can be widely used in large-scale and parallel medicinal chemistry.
Article
Chemistry, Organic
Xiayun Cheng, Alexandria P. Taylor, Kaicheng Zhu
Summary: A one-pot Curtius rearrangement followed by a 6 pi-electrocyclization process has been developed for the synthesis of substituted 2-pyridone products from dienyl carboxylic acids. The dienyl isocyanates generated from aliphatic acids showed higher reactivity compared to their aromatic counterparts, and the substitution patterns of the carboxylic acids influenced the efficiency of the cyclization.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Organic
Weiqiang Li, Qin Wu, Genrui Xu, Yinjing Sun, Chao Huang, Teng Liu
Summary: A practical synthetic approach to access N-aryl/N-alkyl 4-pyridones via a two-step continuous flow process has been developed, which can provide derivatives with a wider substrate scope and good to excellent yields.
ASIAN JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Yu Wang, Yaoyao Xu, Shahid Khan, Zhunjie Zhang, Ajmal Khan
Summary: Regio- and enantioselective amination of readily available vinyl cyclic carbonates with ambivalent 2-hydroxypyridines has been achieved using a Pd(0)/DACH-naphthyl catalyst system. The reaction proceeds under simple conditions, providing access to chiral N-substituted 2-pyridones that bear elusive tertiary carbon centers. This catalytic method overcomes a significant drawback previously associated with transition metal-catalyzed allylic substitution procedures.
NEW JOURNAL OF CHEMISTRY
(2022)
Article
Chemistry, Organic
Xianliang Wang, Marcus Frings, Kari Rissanen, Carsten Bolm
Summary: N-Alkyl sulfoximines react with in situ generated arynes under mild conditions to afford o-sulfinylanilines in good yields. The transformation exhibits a wide substrate scope and excellent functional group tolerance. The structure of a reaction product was confirmed by single-crystal X-ray diffraction.
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Organic
Bo Li, Jun Wu, Lei Tang, Xu Lian, Zhongwen Li, Wenfang Duan, Tong Qin, Xintong Zhao, Yuhua Hu, Chi Zhang, Tianlei Li, Jie Hao, Wenxuan Zhang, Jihong Zhang, Song Wu
Summary: Seventeen C20-O-alkyl/benzyl oxime derivatives were synthesized by a concise and effective method, and showed improved antiproliferative activity against colorectal, gastric, and breast cancer cells compared to salinomycin. The derivatives can coordinate potassium ions and adjust cytosolic Ca2+ concentrations, potentially due to their better ion binding and transport ability. Additionally, they exhibited lower neurotoxic risk, indicating higher selectivity indexes.
ORGANIC & BIOMOLECULAR CHEMISTRY
(2022)
Article
Chemistry, Organic
Biswajit Das, Nilendri Rout, Debayan Sarkar
Summary: This study describes an efficient synthetic strategy using pyridyl C-X activation to generate N-alkyl-2-pyridones from N-alkyl-2-halopyridinium salts. The strategy involves an in-situ generation of Ru(VIII) for catalytic dearomative synthesis of pyridones, which can be further reduced to N-alkyl-2-piperidones. A plausible mechanism is proposed based on controlled reactions.
ASIAN JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Chemistry, Organic
Sen Zhou, Xiaoya Hou, Kai Yang, Minjie Guo, Wentao Zhao, Xiangyang Tang, Guangwei Wang
Summary: A novel method for synthesizing N-difluoromethyl-2-pyridones from readily available pyridines has been described, utilizing mild reaction conditions and identifying N-difluoromethylpyridinium salts as key intermediates in the conversion process.
JOURNAL OF ORGANIC CHEMISTRY
(2021)
Article
Chemistry, Organic
Chao Wang, Yu-Chao Liu, Meng-Yu Xu, Bin Xiao
Summary: An unprecedented cross-coupling reaction of alkyl carbagermatranes with bromofluoroolefins was achieved to deliver dialkyl-substituted monofluoroalkenes, providing an opportunity for challenging molecules with excellent functional group tolerance. The utility of this strategy was demonstrated through the preparation of bioactive agent analogues, including antitubercular agent mimics and COX-2 inhibitor analogues, as well as late-stage fluoroalkenylation of drug-molecule derivatives.
Article
Chemistry, Multidisciplinary
Ling Yang, Dong-Hang Tan, Wen-Xin Fan, Xu-Ge Liu, Jia-Qiang Wu, Zhi-Shu Huang, Qingjiang Li, Honggen Wang
Summary: A new method was proposed utilizing benzyl N-methyliminodiacetyl (MIDA) boronates for photochemical radical C-H halogenation, enabling successful fluorination, chlorination, and bromination reactions. The resulting brominated product could be further transformed into a variety of organic compounds, including those difficult to form with alpha-halo sp(2)-B boronate esters, by reaction with different nucleophiles. An activation effect of the B(MIDA) moiety was discovered.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Organic
Jacek G. Sosnicki, Aleksandra Borzyszkowska-Ledwig, Tomasz J. Idzik, Magdalena M. Lubowicz, Gabriela Maciejewska, Lukasz Struk
Summary: The synthesis of bromo-substituted indeno[1,2-b]-pyridin-2-ones and 3-iodo-5-benzyl-substituted 2-pyridones, starting from easily available 6-benzyl-3,6-dihydropyridin-2(1H)-ones, triggered by NBS and NIS, respectively, was reported. A novel aza-semipinacol-type rearrangement was observed with a transfer of a benzyl group from the C6 to C5 lactam position in both syntheses. The identification of intermediate compounds supported the proposed reaction mechanisms, and functionalized indeno[1,2-b]pyridin-2-ones and 5-benzyl-2-pyridones were obtained during the scope check of the method's application.
Article
Chemistry, Multidisciplinary
Yi Zhang, Zhudi Sun, Jingjing He, Yupian Deng, Ying Liu, Pai Zheng, Song Cao
Summary: A convenient method for the synthesis of N-beta-CF3-substituted 2-pyridones via hydroamination of alpha-(trifluoromethyl)styrenes with 2-pyridones was developed. The reaction proceeded smoothly at room temperature, yielding a variety of N-(beta-trifluoromethyl-beta-arylethyl)pyridin-2(1H)-ones in moderate to good yields with excellent N-regioselectivity.
CHEMISTRY-AN ASIAN JOURNAL
(2023)
Article
Chemistry, Multidisciplinary
Katie Ruffell, Liliana C. Gallegos, Kenneth B. Ling, Robert S. Paton, Liam T. Ball
Summary: This study demonstrates the utility of a modular, bismacycle-based system for the O-selective arylation of 2- and 4-pyridones with arylboronic acids. The research also shows that the kinetically-controlled regioselectivity for O-arylation is attributed to the geometric constraints imposed by the bismacyclic scaffold.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Multidisciplinary
Kangjiang Liang, Xipan Li, Delian Wei, Cuihua Jin, Chuanwang Liu, Chengfeng Xia
Summary: In this study, a new method is reported to remove benzyl-derived protecting groups using visible light irradiation under mild conditions. An excited phenolate-type photocatalyst efficiently transfers an electron to the benzene ring, generating a phenyl radical anion, which then cleaves the benzyl C-N or C-O bond to release a benzyl radical. This method achieves efficient deprotection of the benzyl group in amides, arylamines, ether, ester, and carbamates, with excellent chemo- and regio-selectivity in carbohydrates, peptides, medicines, and natural products with multiple functionalities.
Article
Chemistry, Organic
Ziyue Zhu, Vinayak Krishnamurti, Xanath Ispizua-Rodriguez, Colby Barrett, G. K. Surya Prakash
Summary: A straightforward protocol for direct difluoromethylation of specific organic compounds is presented, showing tolerance towards various functional groups. The selectivity of the reaction can be modulated by simple variations in reaction conditions. Gram-scale reactions for preparing difluoromethyl compounds are demonstrated.
Article
Chemistry, Medicinal
Elizabeth A. Jurica, Ximao Wu, Kristin N. Williams, Andres S. Hernandez, David S. Nirschl, Richard A. Rampulla, Arvind Mathur, Min Zhou, Gary Cao, Chunshan Xie, Biji Jacob, Hong Cai, Tao Wang, Brian J. Murphy, Heng Liu, Carrie Xu, Lori K. Kunselman, Michael B. Hicks, Qin Sun, Dora M. Schnur, Doree F. Sitkoff, Elizabeth A. Dierks, Atsu Apedo, Douglas B. Moore, Kimberly A. Foster, Mary Ellen Cvijic, Reshma Panemangalore, Neil A. Flynn, Brad D. Maxwell, Yang Hong, Yuan Tian, Jason J. Wilkes, Bradley A. Zinker, Jean M. Whaley, Joel C. Barrish, Jeffrey A. Robl, William R. Ewing, Bruce A. Ellsworth
JOURNAL OF MEDICINAL CHEMISTRY
(2017)
Article
Chemistry, Medicinal
Jun Shi, Zhengxiang Gu, Elizabeth Anne Jurica, Ximao Wu, Lauren E. Haque, Kristin N. Williams, Andres S. Hernandez, Zhenqiu Hong, Qi Gao, Marta Dabros, Akin H. Davulcu, Arvind Mathur, Richard A. Rampulla, Arun Kumar Gupta, Ramya Jayaram, Atsu Apedo, Douglas B. Moore, Heng Liu, Lori K. Kunselman, Edward J. Brady, Jason J. Wilkes, Bradley A. Zinker, Hong Cai, Yue-Zhong Shu, Qin Sun, Elizabeth A. Dierks, Kimberly A. Foster, Carrie Xu, Tao Wang, Reshma Panemangalore, Mary Ellen Cvijic, Chunshan Xie, Gary G. Cao, Min Zhou, John Krupinski, Jean M. Whaley, Jeffrey A. Robl, William R. Ewing, Bruce Alan Ellsworth
JOURNAL OF MEDICINAL CHEMISTRY
(2018)
Article
Chemistry, Medicinal
Bruce A. Ellsworth, Wei Meng, Manorama Patel, Ravindar N. Girotra, Gang Wu, Philip M. Sher, Deborah L. Hagan, Mary T. Obermeier, William G. Humphreys, James G. Robertson, Aiying Wang, Songping Han, Thomas L. Waldron, Nathan N. Morgan, Jean M. Whaley, William N. Washburn
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2008)
Article
Pharmacology & Pharmacy
M. Obermeier, M. Yao, A. Khanna, B. Koplowitz, M. Zhu, W. Li, B. Komoroski, S. Kasichayanula, L. Discenza, W. Washburn, W. Meng, B. A. Ellsworth, J. M. Whaley, W. G. Humphreys
DRUG METABOLISM AND DISPOSITION
(2010)
Article
Pharmacology & Pharmacy
Doree F. Sitkoff, Ning Lee, Bruce A. Ellsworth, Qi Huang, Liya Kang, RoseAnn Baska, Yanting Huang, Chongqing Sun, Annapurna Pendri, Mary F. Malley, Raymond P. Scaringe, Jack Z. Gougoutas, Patricia H. Reggio, William R. Ewing, Mary Ann Pelleymounter, Kenneth E. Carlson
EUROPEAN JOURNAL OF PHARMACOLOGY
(2011)
Article
Chemistry, Medicinal
Wei Meng, Bruce A. Ellsworth, Alexandra A. Nirschl, Peggy J. McCann, Manorama Patel, Ravindar N. Girotra, Gang Wu, Philip M. Sher, Eamonn P. Morrison, Scott A. Biller, Robert Zahler, Prashant P. Deshpande, Annie Pullockaran, Deborah L. Hagan, Nathan Morgan, Joseph R. Taylor, Mary T. Obermeier, William G. Humphreys, Ashish Khanna, Lorell Discenza, James G. Robertson, Aiying Wang, Songping Hang, John R. Wetterau, Evan B. Janovitz, Oliver P. Flint, Jean M. Whaley, William N. Washburn
JOURNAL OF MEDICINAL CHEMISTRY
(2008)
Article
Chemistry, Medicinal
Bruce A. Ellsworth, Philip M. Sher, Ximao Wu, Gang Wu, Richard B. Sulsky, Zhengxiang Gu, Natesan Murugesan, Yeheng Zhu, Guixue Yu, Doree F. Sitkoff, Kenneth E. Carlson, Liya Kang, Yifan Yang, Ning Lee, Rose A. Baska, William J. Keim, Mary Jane Cullen, Anthony V. Azzara, Eva Zuvich, Michael A. Thomas, Kenneth W. Rohrbach, James J. Devenny, Helen E. Godonis, Susan J. Harvey, Brian J. Murphy, Gerry G. Everlof, Paul I. Stetsko, Olafur Gudmundsson, Susan Johnghar, Asoka Ranasinghe, Kamelia Behnia, Mary Ann Pelleymounter, William R. Ewing
JOURNAL OF MEDICINAL CHEMISTRY
(2013)
Article
Chemistry, Organic
Sarah Z. Tasker, Michael A. Bosscher, Christina A. Shandro, Erica L. Lanni, Keun Ah Ryu, Gregory S. Snapper, Jarrad M. Utter, Bruce A. Ellsworth, Carolyn E. Anderson
JOURNAL OF ORGANIC CHEMISTRY
(2012)
Article
Chemistry, Applied
Prashant P. Deshpande, Janak Singh, Annie Pullockaran, Thomas Kissick, Bruce A. Ellsworth, Jack Z. Gougoutas, John Dimarco, Michael Fakes, Mayra Reyes, Chiajen Lai, Hidegard Lobinger, Theo Denzel, Peter Ermann, Gerard Crispino, Michael Randazzo, Zenrong Gao, Renee Randazzo, Mark Lindrud, Victor Rosso, Frederic Buono, Wendel W. Doubleday, Simon Leun, Pricilla Richberg, David Hughes, William N. Washburn, Wei Meng, Kevin J. Volk, Richard H. Mueller
ORGANIC PROCESS RESEARCH & DEVELOPMENT
(2012)
Article
Chemistry, Medicinal
Li Xu, Richard A. Hartz, Brett R. Beno, Kaushik Ghosh, Jinal K. Shukla, Amit Kumar, Dipal Patel, Narasimharaju Kalidindi, Nadine Lemos, Shashyendra Singh Gautam, Anoop Kumar, Bruce A. Ellsworth, Devang Shah, Harinath Sale, Dong Cheng, Alicia Regueiro-Ren
Summary: Galectin-3 is involved in cancer, inflammation, and fibrosis, and tetrahydropyran-based Galectin-3 inhibitors have been discovered as potentially valuable disease-modifying agents. Further research on these inhibitors could lead to new therapeutic options for related conditions.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Organic
Michael D. Mandler, Nina Suss, Antonio Ramirez, Christopher A. Farley, Darpandeep Aulakh, Yeheng Zhu, Sarah C. Traeger, Amy Sarjeant, Merrill L. Davies, Bruce A. Ellsworth, Alicia Regueiro-Ren
Summary: An open-air method for the direct amination of nitro(hetero)arenes without transition metals is introduced. It involves the substitution of an aromatic C-H bond through oxidative nucleophilic aromatic substitution of hydrogen (ONSH). Theoretical calculations and mechanistic studies indicate a dianion pathway with oxidation by molecular oxygen as the rate-limiting step.
Article
Chemistry, Organic
Prashant P. Deshpande, Bruce A. Ellsworth, Frederic G. Buono, Annie Pullockaran, Janak Singh, Thomas P. Kissick, Ming-H. Huang, Hildegard Lobinger, Theodor Denzel, Richard H. Mueller
JOURNAL OF ORGANIC CHEMISTRY
(2007)
Article
Chemistry, Medicinal
Bruce A. Ellsworth, Ying Wang, Yeheng Zhu, Annapurna Pendri, Samuel W. Gerritz, Chongqing Sun, Kenneth E. Carlson, Liya Kang, Rose A. Baska, Yifan Yang, Qi Huang, Neil T. Burford, Mary Jane Cullen, Susan Johnghar, Kamelia Behnia, Mary Ann Pelleymounter, William N. Washburn, William R. Ewing
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2007)
Article
Chemistry, Inorganic & Nuclear
BA Ellsworth, AG Doyle, M Patel, J Caceres-Cortes, W Meng, PP Deshpande, A Pullockaran, WN Washburn
TETRAHEDRON-ASYMMETRY
(2003)
