Article
Chemistry, Organic
Lei Dai, Zhou Zhang, Guangzhou Zhu, Yun Liu, Xiaoqin Liu, Jinpeng Zhang, Liangce Rong
Summary: This article describes the Selectfluor-promoted vicinal fluorohydroxylation and hydration reaction of para-quinone methides (p-QMs), which affords vicinal fluorohydrins and ketone/ether products in high yields. The electronic properties of substituents in the aromatic ring highly control the hydration products, and the amount of Selectfluor is significantly different during the synthesis of ketone/ether products. This reaction also marks the first fluorohydroxylation of p-QMs, and the wide range of p-QMs makes the vicinal fluorohydroxylation of great significance.
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Organic
Ze-Yu Tian, Zeng-Hui Lin, Cheng-Pan Zhang
Summary: A selective formal C-H/C-H cross-coupling of azoles and (hetero)arenes was established using arylsulfonium intermediates under transition-metal catalysis, providing a variety of 2-(hetero)aryl azoles in good to excellent yields. The advantages of this reaction include mild reaction conditions, good functional group tolerance, a wide substrate scope, high regio- and chemoselectivity, one-pot procedures, and late-stage functionalization of complex molecules without the use of oxidants, offering a promising strategy for transition-metal-catalyzed C-H arylation of azoles.
Article
Chemistry, Organic
Steve Karreman, Simon B. H. Karnbrock, Sebastian Kolle, Christopher Golz, Manuel Alcarazo
Summary: The synthesis of S-aryl dibenzothiophenium salts and their transformation into 6H-benzo[c]chromenes is achieved through a highly selective reaction pathway, involving photocatalytic single-electron transfer and cyclization of radical intermediates. The mechanistic studies reveal a kinetically favored cyclization pathway and subsequent ring expansion towards the desired tricyclic systems.
Review
Chemistry, Organic
Qing-Zhu Li, Wen-Lin Zou, Zhi-Qiang Jia, Jun-Long Li
Summary: Allyl and propargyl sulfonium salts have emerged as versatile building blocks for the assembly of cyclic skeletons, offering diverse nucleophilic or electrophilic reactive positions for annulation reactions. This growing field presents a comprehensive overview of recent developments and various annulation reactions involving allyl and propargyl sulfonium salts.
SYNTHESIS-STUTTGART
(2021)
Article
Chemistry, Organic
Che-Ming Hsu, Shao-Chi Lee, Hao-En Tsai, Yong-Ting Tsao, Cheng-Lin Chan, Shinje Minoza, Zong-Nan Tsai, Li-Yun Li, Hsuan-Hung Liao
Summary: In this study, we successfully activated the C-S bond in sp(3)-hybridized thiols by introducing a per-/polyfluoroaryl moiety, enabling the efficient removal of sulfur groups and the generation of aliphatic radicals that can react with aryl halides.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Chemistry, Applied
Yushan Xiao, Yimin Jia, Jinfeng Huang, Xiangyu Li, Zhiwen Zhou, Jing Zhang, Mou Jiang, Xin Zhou, Zhong-Xing Jiang, Zhigang Yang
Summary: A metal-free direct trifluoromethylthiolation method has been established for the synthesis of SCF3-substituted sulfonium ylides, using sulfonium salt or alpha-bromoacetic ester as precursors. This method enables the construction of SCF3-substituted sulfonium ylides from a wide range of substrates, including ketones, esters, and PEGylated substrates. The application of this approach in large-scale preparation and the fluorescence and fluorine-19 magnetic resonance imaging capabilities of the product are also explored.
ADVANCED SYNTHESIS & CATALYSIS
(2022)
Article
Chemistry, Organic
Zhen-Hua Wang, Tong Zhang, Qing-Fei Yan, Jian-Qiang Zhao, Yong You, Yan-Ping Zhang, Jun-Qing Yin, Wei-Cheng Yuan
Summary: In this article, various α-aryl vinylsulfonium salts were successfully transformed under mild reaction conditions, leading to the synthesis of diverse 1,2-dihydroquinoline and ring-fused tetrahydroquinoline skeletons with moderate to excellent yields. The potential application of the method was demonstrated by scale-up experiments and further derivatizations of the products. The developed protocol offers mild and transition-metal-free reaction conditions, along with easy operation.
ORGANIC CHEMISTRY FRONTIERS
(2023)
Article
Engineering, Chemical
Laura Adarve-Cardona, Diego Gamba-Sanchez
Summary: In this manuscript, we describe a method for reducing sulfoxides using ethyl vinyl ether/oxalyl chloride. The reaction involves the formation of chlorosulfonium salts, which are highly electrophilic and react with the sulfoxide. The nucleophilic vinyl ether then scavenges the chlorine, resulting in the formation of the corresponding sulfide. This method is suitable for large-scale applications and can be used with highly functionalized sulfoxides. Chromatographic purification is only necessary in special cases, and the final product can usually be obtained by simple evaporation.
Article
Chemistry, Multidisciplinary
Cheng Chen, Minyan Wang, Hongjian Lu, Binlin Zhao, Zhuangzhi Shi
Summary: Alkyl thianthrenium salts have been synthesized as reliable alkylation reagents, which can readily engage in copper-catalyzed Sonogashira and Kumada reactions to build C(sp(3))-C(sp) bonds under mild photochemical conditions. The method demonstrates great functional breadth and compatibility, even with sensitive Cl, Br, and I atoms.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Polymer Science
Shixiong Chen, Chun Cao, Xiaoming Shen, Yiwei Qiu, Cuifang Kuang, Decheng Wan, Ming Jin
Summary: Three sulfonium salt photoinitiators based on 1,3,5-triphenyl-2-pyrazoline were synthesized, and their molecular structures, photophysical and photochemical properties under one/two-photon irradiation were investigated. The study revealed their potential applications in LED photocuring and two-photon 3D microfabrication.
EUROPEAN POLYMER JOURNAL
(2021)
Article
Biochemistry & Molecular Biology
Satenik Mkrtchyan, Michal Jakubczyk, Suneel Lanka, Michael Pittelkow, Viktor O. Iaroshenko
Summary: A synthetic methodology using copper-catalyzed direct arylation was developed for the preparation of aromatic amides from 2-bromo-2,2-difluoroacetamides. The reactions were efficient and successful with aryl groups of various electronic natures, allowing for the rapid preparation of diverse aromatic amides.
Article
Chemistry, Multidisciplinary
Zeyu Feng, Lucas Riemann, Zichen Guo, David Herrero, Martin Simon, Christopher Golz, Ricardo A. A. Mata, Manuel Alcarazo
Summary: The lack of suitable methodologies in the past has hindered the evaluation of the pentafluorocyclopropyl group as a chemotype in crop protection and medicinal chemistry. In this study, a gram-scale synthesis of an unprecedented sulfonium salt was reported, which serves as a versatile reagent for the photoinduced C-H pentafluorocyclopropylation of non-previously functionalized (hetero)arenes through a radical mediated mechanism. The protocol developed demonstrates the scope and potential benefits of introducing the pentafluorocyclopropyl unit into biologically relevant molecules and widely used pharmaceuticals.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Multidisciplinary
Kazuho Ban, Keisuke Imai, Shuki Oyama, Jin Tokunaga, Yui Ikeda, Hiromasa Uchiyama, Kazunori Kadota, Yuichi Tozuka, Shuji Akai, Yoshinari Sawama
Summary: In this study, a novel concept for preparing deuterated reagents was established and the deuterium kinetic isotope effects were demonstrated for the first time. This research has significant implications for drug discovery based on deuterium chemistry.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Chemistry, Applied
Xiaobin Tan, Wenfang Xiong, Baiyao Zhu, Hongjian Liu, Wanqing Wu, Huanfeng Jiang
Summary: Introducing the primary amino group into aromatic ring is a crucial task in organic chemistry, especially in the field of pharmaceuticals and agrochemicals. In this study, we present a photoinduced direct C-H amination of arenes with ammonia using site-selective C-H thianthrenation, which leads to excellent regioselectivity. The reaction conditions are mild and a wide range of functional groups, such as sensitive -Cl, -Br, and -OH groups, can be tolerated, which is challenging in conventional approaches. Moreover, the synthetic utility of our amination protocol has been demonstrated through late-stage modification and gram-scale synthesis of complex drug-like molecules.
ADVANCED SYNTHESIS & CATALYSIS
(2023)
Article
Chemistry, Multidisciplinary
Shibiao Tang, Xiaobo Zhao, Lidong Yang, Bin Li, Baiquan Wang
Summary: An efficient copper-catalyzed carboxylation of aryl thianthrenium salts with carbon dioxide at room temperature is developed, providing an effective method for the site-selective C-H carboxylation of aromatic hydrocarbons.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Radiology, Nuclear Medicine & Medical Imaging
Ahmed Haider, Susan Bengs, Angela Portmann, Alexia Rossi, Hazem Ahmed, Dominik Etter, Geoffrey Warnock, Nidaa Mikail, Muriel Gramer, Alexander Meisel, Livio Gisler, Caitlin Jie, Claudia Keller, Sebastian Kozerke, Bruno Weber, Roger Schibli, Linjing Mu, Philipp A. Kaufmann, Vera Regitz-Zagrosek, Simon M. Ametamey, Catherine Gebhard
Summary: This study aimed to assess the impact of female and male sex hormones on myocardial perfusion and coronary flow reserve. The experimental data in mice indicate that testosterone plays a primary role in sex differences in myocardial perfusion.
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
(2022)
Article
Cardiac & Cardiovascular Systems
Susan Bengs, Geoffrey Warnock, Angela Portmann, Nidaa Mikail, Alexia Rossi, Hazem Ahmed, Dominik Etter, Valerie Treyer, Livio Gisler, Stefanie K. Pfister, Caitlin V. M. L. Jie, Alexander Meisel, Claudia Keller, Steven H. Liang, Roger Schibli, Linjing Mu, Ronny R. Buechel, Philipp A. Kaufmann, Simon M. Ametamey, Catherine Gebhard, Ahmed Haider
Summary: This study demonstrates the feasibility of using F-18-flurpiridaz for simplified assessment of relative myocardial perfusion and coronary flow reserve in mice, enabling high-throughput mechanistic CFR studies in rodents.
JOURNAL OF NUCLEAR CARDIOLOGY
(2023)
Article
Radiology, Nuclear Medicine & Medical Imaging
Yun Qin, Stefan Imobersteg, Stephan Frank, Alain Blanc, Tanja Chiorazzo, Philipp Berger, Roger Schibli, Martin P. Behe, Michal Grzmil
Summary: α-particle emitters have potential as therapeutic radionuclides, but toxicity and radioresistance limit their efficacy. This study identified the radiation-activated mechanisms driving cancer cell survival, providing opportunities for therapeutic interference to improve the efficacy and safety of α-particle therapy.
JOURNAL OF NUCLEAR MEDICINE
(2023)
Review
Oncology
Michal Grzmil, Fabius Wiesmann, Roger Schibli, Martin Behe
Summary: Targeted radionuclide therapy (TRT) is a cancer treatment that delivers cancer-selective radiopharmaceuticals to destroy cancer cells without harming healthy tissue. This review focuses on the use of mTORC1 inhibition to improve the efficacy of TRT by delivering radiolabeled ligands. It discusses the rationale, efficacy, and safety of this combinatorial approach in cancer patients.
Article
Chemistry, Medicinal
Melanie Zechner, Claudia A. Castro Jaramillo, Nadine S. Zubler, Marco F. Taddio, Linjing Mu, Karl-Heinz Altmann, Stefanie D. Kramer
Summary: Breast cancer resistance protein (BCRP, ABCG2) is a crucial efflux transporter involved in multidrug resistance to antineoplastic drugs. Ko143, an analogue of fumitremorgin C, is a potent ABCG2 inhibitor but is rapidly metabolized in vivo. In order to find ABCG2 inhibitors with improved metabolic stability, a series of Ko143 analogues were evaluated for their ability to inhibit ABCG2-mediated transport in cells and assessed for stability in liver microsomes. The most promising analogues increased the distribution of [11C]tariquidar, an ABCG2/ABCB1 substrate, to the brain in animal models.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Radiology, Nuclear Medicine & Medical Imaging
Chiara Favaretto, Pascal Grundler, Zeynep Talip, Stefan Landolt, Lebogang Sepini, Ulli Koster, Cristina Muller, Roger Schibli, Susanne Geistlich, Nicholas P. van der Meulen
Summary: This study aimed to characterize and specify 161Tb, as well as develop a protocol for the synthesis and quality control of 161Tb-DOTATOC for clinical use. Results showed that 161Tb met the clinical requirements in terms of chemical purity, radionuclidic purity, and endotoxin level. A highly efficient procedure for the automated production and quality control of 161Tb-DOTATOC was developed. This study provides valuable insights for the application of 161Tb in radionuclide therapy.
JOURNAL OF NUCLEAR MEDICINE
(2023)
Article
Medicine, Research & Experimental
Rahel H. Wallimann, Patrick Schindler, Heloise Hensinger, Viviane J. Tschan, Sarah D. Busslinger, Rainer Kneuer, Cristina Muller, Roger Schibli
Summary: The study investigates whether inductively coupled plasma mass spectrometry (ICP-MS) can be used to predict the properties of radiopharmaceuticals by characterizing non-radioactive metal conjugates. The results show that ICP-MS and conventional gamma-counting provide almost identical results for in vitro and in vivo uptake and internalization of the metal conjugates. Therefore, ICP-MS can be considered as a reliable alternative to gamma-counting for the detection and quantification of radioactive ligands.
MOLECULAR PHARMACEUTICS
(2023)
Article
Radiology, Nuclear Medicine & Medical Imaging
Darja Beyer, Christian Vaccarin, Xavier Deupi, Ana Katrina Mapanao, Susan Cohrs, Fan Sozzi-Guo, Pascal V. Grundler, Nicholas P. van der Meulen, Jinling Wang, Matthias Tanriver, Jeffrey W. Bode, Roger Schibli, Cristina Mueller
Summary: This study developed an ACE2-targeting imaging agent to determine ACE2 regulation. The radiopeptide [Ga-67]Ga-HBED-CC-DX600 showed the most favorable tissue distribution profile.
Article
Chemistry, Multidisciplinary
Faustine d'Orchymont, Jason P. Holland
Summary: We synthesized and characterized bimodal mechanically interlocked rotaxane-based imaging agents using the cucurbit[6]uril CB[6]-mediated alkyne-azide 'click' reaction. Two synthetic routes involving four- or six-component reactions were developed to access asymmetric rotaxanes. A peptide-based rotaxane targeted toward the clinical prostate cancer biomarker, prostate-specific membrane antigen (PSMA), was synthesized with Ga-68-radiometal ion complex for positron emission tomography and fluorescein as an optically active imaging agent. The results showed the feasibility of using an asymmetric rotaxane platform to produce dual-modality imaging agents specifically targeting prostate cancer cells.
COMMUNICATIONS CHEMISTRY
(2023)
Article
Chemistry, Inorganic & Nuclear
Ina Hierlmeier, Amaury Guillou, Daniel F. Earley, Anthony Linden, Jason P. Holland, Mark D. Bartholomae
Summary: In this study, we synthesized and investigated the coordination chemistry of novel copper(II) and zinc(II) complexes using two heterocyclic triazacyclononane(tacn)-based chelators (HNODThia and NODThia-AcNHEt). The modified chelator HNODThia was used to develop a PSMA-based bioconjugate (NODThia-PSMA) and a photoactivatable azamacrocyclic analogue (NODThia-PEG ( 3 ) -ArN ( 3 )) for copper-64 radiopharmaceuticals. The metal-binding chelates showed rapid radiolabeling, stability in human plasma, and successful photoconjugation to albumin and antibodies. These findings have significant implications for the development of stable Cu-64-based radiopharmaceuticals and the future application of Cu-67 in targeted radioimmunotherapy.
INORGANIC CHEMISTRY
(2023)
Article
Oncology
Sarah D. Busslinger, Anna E. Becker, Christian Vaccarin, Luisa M. Deberle, Marie-Luise Renz, Viola Groehn, Roger Schibli, Cristina Muller
Summary: This study revealed that modification with an albumin-binding moiety can enhance blood residence time of radiopharmaceuticals, affecting their tissue distribution profiles. Different albumin binders and linker units can fine-tune the pharmacokinetic properties of radioconjugates for optimal tumor uptake and distribution. Subtle changes in the albumin-binding entity and linker unit can lead to significant differences in blood retention and kidney accumulation of radiopharmaceuticals.
Article
Agriculture, Dairy & Animal Science
Lavinia E. Chiti, Brian Park, Faustine d'Orchymont, Jason P. Holland, Mirja C. Nolff
Summary: The use of near-infrared fluorophores has promising applications in surgical oncology. The performance of dedicated camera systems is affected by the lighting condition of the operating theatre. LED and halogen lights have a detrimental effect on the diagnostic performances of the camera systems. Surgeons should evaluate the spectral contribution of the lights when implementing fluorescence-guided surgery (FGS) into the clinical routine.
Article
Biochemistry & Molecular Biology
Melanie Gut, Birgit Dreier, Sven Furler, Jens Sobek, Andreas Pluckthun, Jason P. Holland
Summary: Late-stage prostate cancer often becomes resistant to standard chemotherapy and transforms into a hormone-resistant, drug-resistant, and incurable disease. Developing non-invasive tools to detect biochemical changes that indicate drug efficacy and identify drug resistance could have significant implications in managing individual patients' treatment plans. In this study, new Designed Ankyrin Repeat Proteins (DARPins) with high affinity for prostate-specific antigen (PSA) were selected using ribosome display and in vitro screening tools. These PSAbinding DARPins showed nanomolar affinity for PSA and could be radiolabeled for potential use in imaging-based monitoring of androgen receptor (AR)-targeted therapies.
RSC CHEMICAL BIOLOGY
(2023)
Article
Biochemical Research Methods
Yingqing Lu, Yingfang He, Roger Schibli, Linjing Mu, R. Michael van Dam
Summary: Copper-mediated radiofluorination has great potential in the synthesis of PET radioligands. We demonstrated the feasibility of Cu-mediated radiosynthesis on a high-throughput microdroplet platform and optimized the reaction conditions. By utilizing microscale conditions, we achieved higher radiochemical yield and excellent radiochemical purity and molar activity. We also successfully translated these optimized conditions to a vial-based method, expanding the applicability of the synthesis approach.
