Article
Chemistry, Physical
Francisco Gaspar, Guilherme S. Caleffi, Paulo C. T. Costa-Junior, Paulo R. R. Costa
Summary: The Noyori-Ikariya Ru-II complexes were utilized to promote the reduction of C=C/C=O bonds in isoflavones, leading to selective formation of cis-3-phenylchroman-4-ols with different substituents at the 2' position of the B-ring in high yields and excellent enantioselectivities. New synthetic strategies for obtaining enantioenriched isoflavanones and pterocarpans were also demonstrated in this study, showcasing the versatility of the developed method.
Article
Chemistry, Physical
Masa Sterle, Matej Hus, Matic Lozinsek, Anamarija Zega, Andrej Emanuel Cotman
Summary: Stereopure CF3-substituted syn-1,2-diols were synthesized through the reductive dynamic kinetic resolution of corresponding alkyl ketones, yielding products with >95% ee and >87:13 syn/anti ratio. This method provides a rapid access to stereopure bioactive molecules. Moreover, DFT calculations were conducted on three types of Noyori-Ikariya ruthenium catalysts to demonstrate their general ability to control stereoselectivity through hydrogen bond acceptor SO2 region and CH/pi interactions.
Article
Biochemistry & Molecular Biology
Ricardo Molina Betancourt, Phannarath Phansavath, Virginie Ratovelomanana-Vidal
Summary: A practical method for the asymmetric transfer hydrogenation/dynamic kinetic resolution of N-Boc 3-fluoro-dihydrotetrahydroquinolin-4-ones into the corresponding cis-fluoro alcohols is reported. The reaction achieved high yields, up to 99:1 diastereomeric ratio (dr), and up to >99% enantiomeric excess (ee) by using a ruthenium complex and a formic acid/triethylamine mixture under mild conditions.
Article
Chemistry, Organic
Lucas Bacheley, Ricardo Molina Betancourt, Rathies Ravindra, Gerard Guillamot, Phannarath Phansavath, Virginie Ratovelomanana-Vidal
Summary: A straightforward method for synthesizing novel families of enantioenriched cis-monofluorinated carbocyclic alcohols has been developed using ATH/DKR. The reaction exhibited high yields (up to 97%), high diastereoselectivity (up to 99:1 dr), and high enantioselectivity (up to 97% ee). Additionally, trans-difluorinated indans, tetrahydronaphthalenes, tetrahydroquinolines, and chromans were synthesized via deoxofluorination of the corresponding cis-fluoro alcohols.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Multidisciplinary
Shu-Xin Zhang, Cong Xu, Niannian Yi, Shan Li, Yan-Mei He, Yu Feng, Qing-Hua Fan
Summary: This study successfully achieved the highly efficient ruthenium-catalyzed enantioselective hydrogenation of 9-phenanthrols by trapping the unstable keto tautomers under mild conditions. The method provides a facile access to chiral 9,10-dihydrophenanthren-9-ols with high yield and enantiomeric excess.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Multidisciplinary
Daniel J. Tindall, Steffen Mader, Alois Kindler, Frank Rominger, A. Stephen K. Hashmi, Thomas Schaub
Summary: Sugar alcohols are important for the food industry and can be produced in large quantities with increased yield and stereoselectivity through a homogeneous system.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Inorganic & Nuclear
Zheng Wang, Ning Ma, Xiaochi Lu, Ming Liu, Tian Liu, Qingbin Liu, Gregory A. Solan, Wen-Hua Sun
Summary: A series of manganese(i) carbonyl complexes with structurally related NN- and NNN-chelating ligands were synthesized and used as catalysts for transfer hydrogenation. The NN-systems based on N-R functionalized 5,6,7,8-tetrahydroquinoline-8-amines showed the highest catalytic activity in the conversion of acetophenone to 1-phenylethanol. The N-isopropyl derivative, Mn1, when combined with t-BuONa, achieved efficient reduction of acetophenone and various carbonyl substrates, with high TON values (up to 17,200; TOF of 3550 h(-1)). These findings support an outer-sphere mechanism for the hydrogen transfer and provide a sustainable alternative for producing alcoholic products from carbonyl substrates.
DALTON TRANSACTIONS
(2023)
Review
Chemistry, Inorganic & Nuclear
Han Peng, Vincent Ritleng, Christophe Michon
Summary: This article reviews the development of supported Noyori-Ikariya catalysts based on ruthenium, rhodium, and iridium for asymmetric transfer hydrogenation and related tandem reactions over the past 7 years. It highlights and discusses the synthesis, reactivity, and recycling of these catalysts.
COORDINATION CHEMISTRY REVIEWS
(2023)
Review
Chemistry, Multidisciplinary
Andrej Emanuel Cotman
Summary: Noyori-Ikariya-type ruthenium(II)-catalysts have been used for 25 years in asymmetric transfer hydrogenation for the synthesis of chiral secondary alcohols. Recent progress has been made in understanding the asymmetric reduction of complex ketones, controlling up to four stereocenters in a single transformation. Intriguing multi-chiral molecular architectures can be prepared via ATH for drug discovery.
CHEMISTRY-A EUROPEAN JOURNAL
(2021)
Article
Chemistry, Inorganic & Nuclear
Zheng Wang, Yahuan Liu, Mingyang Han, Ning Ma, Quanming Lyu, Qingbin Liu, Wen-Hua Sun
Summary: Molybdenum complexes with various structural features were developed and showed high activity in the transfer hydrogenation reaction. The products can be easily purified by removing the byproduct.
DALTON TRANSACTIONS
(2022)
Article
Chemistry, Organic
Thomas H. Hall, Hannah Adams, Vijyesh K. Vyas, K. L. Michael Chu, Martin Wills
Summary: A detailed study was conducted on the asymmetric transfer hydrogenation (ATH) of a series of enones using Ru(II) catalysts. The ATH reaction can readily discriminate between double and triple bonds adjacent to ketones, reducing the double bond but leaving a triple bond intact in the major product.
Article
Chemistry, Organic
Yin-Bo Wan, Xiang-Ping Hu
Summary: A readily available and highly modular class of chiral P,N,N-ligands have been developed and successfully applied in the Ir-catalyzed asymmetric hydrogenation. These ligands exhibited excellent activity, enantioselectivity, and substrate tolerance, thus providing optically active compounds with high yields and enantioselectivities. This study demonstrates the utility of these ligands in diverse product transformation and the synthesis of biologically active compounds.
Article
Chemistry, Physical
Lixian Wang, Jin Lin, Qiangsheng Sun, Chungu Xia, Wei Sun
Summary: A series of Mn(I) catalysts with chiral bidentate benzimidazoles derived from easily available amino acids have been developed for asymmetric transfer hydrogenation (ATH), showing high activity and enantioselectivity. These phosphine-free chiral Mn catalysts can efficiently convert bulky substrates into drug intermediate alcohols, with a possible mechanism and enantiocontrol model proposed based on experimental and DFT studies.
Article
Chemistry, Multidisciplinary
Guang-Ya Zhang, Sun-Hong Ruan, Yan-Yun Li, Jing-Xing Gao
Summary: The study investigated the asymmetric transfer hydrogenation of a wide range of ketones catalyzed by manganese complex and chiral PxNy-type ligand under mild conditions. By using 2-propanol as a hydrogen source and combining [MnBr(CO)(5)] with chiral, 22-membered macrocyclic ligand (R,R,R',R')-CyP2N4 (L5) with 2% catalyst loading, various ketones could be enantioselectively hydrogenated to afford highly valuable chiral alcohols with up to 95% ee.
CHINESE CHEMICAL LETTERS
(2021)
Article
Chemistry, Organic
Chengyi Wang, Shaomin Deng, Rui Chen, Guohua Liu, Tanyu Cheng, Rui Liu
Summary: A mechanochemical asymmetric transfer hydrogenation (ATH) of diketones has been developed under solvent-free conditions with a ruthenium complex, leading to chiral 1,3-diol derivatives. This method offers advantages such as rapid reaction kinetics, no solvent requirement, and excellent enantioselectivity.
Article
Chemistry, Applied
David Moe Almenningen, Henrik Erring Hansen, Martin Furru Vold, Audun Formo Buene, Vishwesh Venkatraman, Svein Sunde, Bard Helge Hoff, Odd Reidar Gautun
Summary: In this study, the effect of pi-spacers on dye performance in DSSCs was investigated by synthesizing five novel phenothiazine dyes with varying numbers of thiophenes in the pi-spacer. The light absorption properties of the dye were significantly improved when the number of thiophenes was two or more. However, incorporating larger oligothiophenes proved to be detrimental to DSSC performance, with the reference dye without a pi-spacer demonstrating the best overall performance.
Article
Chemistry, Organic
Fredrik Heen Blindheim, Cecilie Elisabeth Olsen, Caroline Krogh Sogaard, Marit Otterlei, Eirik Sundby, Bard Helge Hoff
Summary: Imidazopyridinones and 7-azaoxindoles, two classes of heterocyclic compounds, have shown potent inhibition and low activity respectively, with the former being more challenging to prepare and the latter exhibiting poor cell wall penetration.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2021)
Review
Chemistry, Multidisciplinary
Sihai Luo, Bard H. Hoff, Stefan A. Maier, John C. de Mello
Summary: This study evaluates some of the most promising techniques for nanogap fabrication, including traditional methods like photolithography, electron-beam lithography, and focused ion beam milling, as well as newer methods using novel electrochemical and mechanical means for patterning. The physical principles behind each method are reviewed, and their strengths and limitations for nanogap patterning are discussed in terms of resolution, fidelity, speed, ease of implementation, versatility, and scalability to large substrate sizes.
Article
Chemistry, Multidisciplinary
Fredrik Heen Blindheim, Ane Thoresen Malme, Bjorn Dalhus, Eirik Sundby, Bard Helge Hoff
Summary: A substance with activity against E. coli TMPK was discovered and led to the synthesis and screening of effective derivatives, two of which showed promising drug-like properties and selectivity for E. coli TMPK.
Article
Chemistry, Multidisciplinary
David Moe Almenningen, Brita Susanne Haga, Henrik Erring Hansen, Audun Formo Buene, Bard Helge Hoff, Odd Reidar Gautun
Summary: A novel concept of tethering an anti-aggregation unit to dyes for dye-sensitized solar cells (DSSCs) was introduced. The study demonstrates the successful increase in photovoltages in devices employing copper-based electrolytes by decorating the donor dye with a steric ethyladamantyl moiety. The best photovoltaic performance was achieved by combining the adamantyl decorated donor dye with CDCA, showcasing the potential of ethyladamantyl side chains for surface protection of TiO2.
CHEMISTRY-A EUROPEAN JOURNAL
(2022)
Article
Infectious Diseases
Cecilie Elisabeth Olsen, Fredrik Heen Blindheim, Caroline Krogh Sogaard, Lisa Marie Rost, Amanda Holstad Singleton, Olaug Elisabeth Torheim Bergum, Per Bruheim, Marit Otterlei, Eirik Sundby, Bard Helge Hoff
Summary: There is a global rise in antibiotic resistance, which burdens individuals and public healthcare systems, while drug development lags behind. Therefore, finding new ways of treating bacterial infections, such as identifying new agents or combinations of drugs, is crucial. Combination therapy based on agents with different modes of action can reduce the development of resistance.
Article
Chemistry, Multidisciplinary
David Moe Almenningen, Veslemoy Minge Engh, Eivind Andreas Stromsodd, Henrik Erring Hansen, Audun Formo Buene, Bard Helge Hoff, Odd Reidar Gautun
Summary: The geometry of a dye has significant impact on the properties of dye-sensitized solar cells. This study investigates the effect of planarizing the geometry of a common triarylamine donor in dyes for DSSC. Five novel dyes were designed and synthesized, and it was found that planarization can improve absorption properties. However, incorrect linking of donor and acceptor moieties has a negative effect. The structure of the dye also affects charge recombination. The best performance was achieved by a dye with furan as a pi-spacer, reaching a power conversion efficiency of 5.2%.
Article
Chemistry, Applied
Eivind Andreas Stromsodd, Audun Formo Buene, David Moe Almenningen, Odd Reidar Gautun, Bard Helge Hoff
Summary: The Suzuki-Miyaura cross-coupling reaction is a convenient method for preparing thienyl-containing dyes and bioactive molecules. However, using thienylboronic acids in these reactions can present challenges. In this study, we investigated the cross-coupling of (5-formylthiophen-2-yl)boronic acid with 4-bromoanisole as a model reaction to gain a deeper understanding. We explored variations in catalyst, base, aryl halide type, temperature, and reaction medium. The results showed that a highly active catalyst and sufficient solubility of both the boronic acid and the aryl halide were crucial for successful cross-coupling reactions. XPhos precatalysts were found to be the most effective system for the model reaction, and other catalysts could also be used with higher amounts of boronic acid or an aryl iodide as the cross-coupling partner. The XPhos 4th generation precatalyst was also efficient for constructing various compounds such as mono- and di-thiophene-2-carbaldehyde substituted phenothiazines and a triarylamine dye precursor. However, fine tuning of the reaction medium was necessary for each cross-coupling pair to maximize the yield.
Article
Biochemistry & Molecular Biology
Frithjof Bjornstad, Eirik Sundby, Bard Helge Hoff
Summary: Lithiation-addition at C-6 of protected 4-chloro-7H-pyrrolo [2,3-d]pyrimidine was investigated as a route to new building blocks for medicinal chemistry. The use of bis(2-dimethylaminoethyl) ether as an additive increased the yield in the additional reaction with benzaldehyde. The protocol showed good compatibility with aldehydes, cyclohexanone derivatives, and 2,2,2-trifluoroacetophenone, but was less efficient for acetophenones, with yields ranging from 46-93%.
Article
Chemistry, Organic
Thomas I. Aarhus, Vilde Teksum, Anke Unger, Peter Habenberger, Alexander Wolf, Jan Eickhoff, Bert Klebl, Camilla Wolowczyk, Geir Bjorkoy, Eirik Sundby, Bard H. Hoff
Summary: The colony-stimulating factor 1 receptor (CSF1R) is identified as a potential therapeutic target in cancer, CNS, and inflammatory diseases. Molecular docking and synthesis studies have led to the discovery of low molecular weight compounds that show promise as lead candidates for optimization. These compounds are synthesized from a 4-chloro-6-iodo-pyrrolo[2,3-d]pyrimidine building block using Negishi and Suzuki-Miyaura cross-coupling reactions with high yields. Several inhibitors exhibit excellent enzymatic potency, with the parent compound preferentially binding to the autoinhibited form of CSF1R. Cellular and in vivo profiling suggest further structural tuning is required before efficacy studies.
EUROPEAN JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Thomas Ihle Aarhus, Frithjof Bjornstad, Camilla Wolowczyk, Kristin Uhlving Larsen, Line Rognstad, Trygve Leithaug, Anke Unger, Peter Habenberger, Alexander Wolf, Geir Bjorkoy, Clare Pridans, Jan Eickhoff, Bert Klebl, Bard H. Hoff, Eirik Sundby
Summary: Colony-stimulating factor-1 receptor (CSF1R) is a receptor tyrosine kinase that can be inhibited for potential therapy in human disorders. Highly selective pyrrolo-[2,3-d]-pyrimidines were synthesized and developed in this study, showing subnanomolar enzymatic inhibition of CSF1R with excellent selectivity towards other kinases. The crystal structure analysis revealed the binding conformation of the protein, and the most promising compounds were evaluated for cellular potency, pharmacokinetic profiling, and in vivo stability, suggesting their relevance in disease treatment. Furthermore, these compounds primarily inhibited the autoinhibited form of the receptor, showing exquisite selectivity unlike pexidartinib.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Thomas Ihle Aarhus, Jan Eickhoff, Bert Klebl, Anke Unger, Joanna Boros, Axel Choidas, Mia -Lisa Zischinsky, Camilla Wolowczyk, Geir Bjorkoy, Eirik Sundby, Bard Helge Hoff
Summary: Through modelling, synthesis, and systematic structure-activity relationship study, a number of potent and highly selective purine-based inhibitors of CSF1R have been identified. Compound 9, the optimized 6,8-disubstituted antagonist, shows enzymatic IC50 of 0.2 nM and strong affinity towards the autoinhibited form of CSF1R.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Organic
Fuying Zhu, Yamei Lin
Summary: In this study, a low-metal iron-supported catalyst (Fe20/NC-Mg) was reported for the efficient synthesis of quinoxaline compounds, using water as a solvent and without additional bases. The synergistic effect of FeNx site and Mg (OH)2 nanorods in the catalyst played a key role in achieving high yields (82-91%) in 16 examples. The gram-level synthesis and reusability of the catalysts after four cycles demonstrated its industrial application potential.
Article
Chemistry, Organic
Mikhail Kozlov, Alexey Tyurin, Andrey Dmitrenok, Vyacheslav Rusak, Aleksander Fedorov, Igor Zavarzin, Yulia Volkova
Summary: This study presents a novel and practical synthesis method for phosphorus-substituted 1,3,4-thiadiazolines using phosphorylthioformic acid hydrazides and ketones. The protocol demonstrates operational simplicity, availability of reagents, and tolerance towards different functional groups.
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.
