10,361 results on '"oxime"'
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2. Novel Tryptanthrin Derivatives with Selectivity as c–Jun N–Terminal Kinase (JNK) 3 Inhibitors
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Quinn, Igor A. Schepetkin, Oleksander S. Karpenko, Anastasia R. Kovrizhina, Liliya N. Kirpotina, Andrei I. Khlebnikov, Stepan I. Chekal, Alevtyna V. Radudik, Maryna O. Shybinska, and Mark T.
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anti-inflammatory ,c-Jun N-terminal kinase ,molecular docking ,nuclear factor-κB ,oxime ,selective kinase inhibitor ,tryptanthrin - Abstract
The c-Jun N-terminal kinase (JNK) family includes three proteins (JNK1-3) that regulate many physiological processes, including cell proliferation and differentiation, cell survival, and inflammation. Because of emerging data suggesting that JNK3 may play an important role in neurodegenerative diseases, such as Alzheimer’s disease (AD) and Parkinson’s disease, as well as cancer pathogenesis, we sought to identify JNK inhibitors with increased selectivity for JNK3. A panel of 26 novel tryptanthrin-6-oxime analogs was synthesized and evaluated for JNK1-3 binding (Kd) and inhibition of cellular inflammatory responses. Compounds 4d (8-methoxyindolo[2,1-b]quinazolin-6,12-dione oxime) and 4e (8-phenylindolo[2,1-b]quinazolin-6,12-dione oxime) had high selectivity for JNK3 versus JNK1 and JNK2 and inhibited lipopolysaccharide (LPS)-induced nuclear factor-κB/activating protein 1 (NF-κB/AP-1) transcriptional activity in THP-1Blue cells and interleukin-6 (IL-6) production by MonoMac-6 monocytic cells in the low micromolar range. Likewise, compounds 4d, 4e, and pan-JNK inhibitor 4h (9-methylindolo[2,1-b]quinazolin-6,12-dione oxime) decreased LPS-induced c-Jun phosphorylation in MonoMac-6 cells, directly confirming JNK inhibition. Molecular modeling suggested modes of binding interaction of these compounds in the JNK3 catalytic site that were in agreement with the experimental data on JNK3 binding. Our results demonstrate the potential for developing anti-inflammatory drugs based on these nitrogen-containing heterocyclic systems with selectivity for JNK3.
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- 2023
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3. A copper-catalyzed three-component reaction of alkenes, cycloketone oximes and DABCO·(SO2)2: Direct C(sp2)-H cyanoalkylsulfonylation
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Ling-Hui Zeng, Yating Liu, Jie Wu, Tonghao Zhu, Yun Zhao, and Luoyu Wang
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chemistry.chemical_compound ,chemistry ,Component (thermodynamics) ,Functional group ,Substrate (chemistry) ,Stereoselectivity ,General Chemistry ,DABCO ,Oxime ,Medicinal chemistry ,Sulfur dioxide ,Bond cleavage - Abstract
A copper-catalyzed three-component reaction of alkenes, cycloketone oximes and DABCO•(SO2)2 is developed, which provides a convenient route for the synthesis of diverse (E)-cyanoalkylsulfonyl alkenes in moderate to good yields with excellent regio- and stereoselectivity. A broad substrate scope with excellent functional group tolerance is observed. A plausible radical pathway is proposed, which involves copper-catalyzed ring-opening C-C bond cleavage of O-acyl oxime and insertion of sulfur dioxide. During the reaction process, cyanoalkyl radical and cyanoalkylsulfonyl radical are the key intermediates.
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- 2022
4. Synthesis of nitrogen-containing oleanolic acid derivatives as carbonic anhydrase and acetylcholinesterase inhibitors
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Halil Şenol, Gurbet Çelik Turgut, Alaattin Şen, Rüya Sağlamtaş, Salih Tuncay, İlhami Gülçin, Gülaçtı Topçu, and ŞENOL, HALIL
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Kimya (çeşitli) ,Temel Bilimler (SCI) ,Pharmacy ,ÇOK DİSİPLİNLİ BİLİMLER ,Sağlık Bilimleri ,Organik Kimya ,Kimya ,Clinical Medicine (MED) ,Oxime ,Pharmaceutical Chemistry ,Isoenzymes I ,CHEMISTRY ,FARMAKOLOJİ VE ECZACILIK ,Klinik Tıp (MED) ,Pharmacology (medical) ,General Pharmacology, Toxicology and Pharmaceutics ,PHARMACOLOGY & PHARMACY ,Pharmacology, Toxicology and Pharmaceutics (miscellaneous) ,PHARMACOLOGY & TOXICOLOGY ,Carbonic anhydrase ,Multidisciplinary ,Temel Bilimler ,Life Sciences ,Ursolic Acids ,CHEMISTRY, ORGANIC ,Hydrazone ,Genel Farmakoloji, Toksikoloji ve Eczacılık ,Farmakoloji (tıbbi) ,İlaç Rehberleri ,Chemistry (miscellaneous) ,Farmakoloji ve Toksikoloji ,Natural Sciences (SCI) ,Physical Sciences ,Acetylcholinesterase ,Natural Sciences ,Farmasötik Kimya ,Farmakoloji ,Life Sciences (LIFE) ,Doğal Ürünler Kimyası ,Chemistry of Natural Products ,Meslek Bilimleri ,Imine ,KİMYA, ORGANİK ,Drug Guides ,Health Sciences ,Yaşam Bilimleri ,Professional Sciences ,Farmakoloji, Toksikoloji ve Eczacılık (çeşitli) ,Eczacılık ,Pharmacology ,Crystal-Structure ,Multidisipliner ,MULTIDISCIPLINARY SCIENCES ,Organic Chemistry ,Doğa Bilimleri Genel ,Oleanolic acid ,General Chemistry ,Triterpenoids ,Pharmacology and Therapeutics ,Glycosidase ,Genel Kimya ,NATURAL SCIENCES, GENERAL ,Fizik Bilimleri ,Yaşam Bilimleri (LIFE) ,Butyrylcholinesterase ,Alpha-Glucosidase ,Dementia ,Biological Evaluation ,Analogs - Abstract
In this study, a total of 13 compounds (5-17) were synthesized starting from oleanolic acid (OA), a natural triterpenoid. Five new compounds (10, 11, 12, 15 and 17), are the main targets of the study, which were synthesized for the first time in this work as oxime, imine and hydrazone derivatives of OA. Other compounds were previously obtained as natural or semi-synthetically. NMR and HRMS analyses were carried out to determine of structures of all the synthesized molecules. The inhibitory effects of the synthesized compounds on acetylcholinesterase (AChE), human carbonic anhydrase I (hCA I) and II (hCA II) were evaluated. Compounds 13 and 15 showed better inhibitory activity than the other compounds against both hCA I and hCA II isoenzymes, which are competing with AZA. In addition, compound 15 showed the strongest AChE inhibitory activity among all the tested compounds, with an IC50 value of 34.46 mu M.
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- 2023
5. Iron-catalyzed cyanoalkylation of difluoroenol silyl ethers with cyclobutanone oxime esters
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Yangen Huang, Xiu-Hua Xu, Feng-Ling Qing, and Xiao-Lei Zhu
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chemistry.chemical_compound ,chemistry ,Silylation ,Iron catalyzed ,Organic chemistry ,Cyclobutanone ,General Chemistry ,Oxime ,Coupling reaction - Abstract
An iron-catalyzed coupling reaction of difluoroenol silyl ethers and cyclobutanone oxime esters is described. This protocol provides a convenient access to various previously unknown and potentially useful gem-difluoromethylenated ketonitriles inmoderate to good yields. The transformations of resulting products to other fluorinecontaining products is also documented.
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- 2022
6. Synthesis, Molecular Docking, BSA, and In Vitro Reactivation Study of Imidazopyridine Oximes Against Paraoxon Inhibited Acetylcholinesterase
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Ashima Thakur, Swaran J.S. Flora, Abha Sharma, and Jayant Patwa
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Obidoxime ,Imidazopyridine ,biology ,Paraoxon ,Chemistry ,AutoDock ,Oxime ,Combinatorial chemistry ,Acetylcholinesterase ,Binding constant ,chemistry.chemical_compound ,Drug Discovery ,medicine ,biology.protein ,Bovine serum albumin ,medicine.drug - Abstract
Aim: To synthesize and evaluate the fused heterocyclic imidazopyridine oxime as a reactivator against paraoxon inhibited acetylcholinesterase. Background: Organophosphorus compounds (OPs) include parathion, malathion, chlorpyrifos, monocrotophos, and diazinon which are commonly used in agriculture for enhancing agricultural productivity via killing crop-damaging pests. However, people may get exposed to OPs pesticides unintentionally/intentionally via ingestion, inhalation or dermal. The current treatment regimen includes reactivator such as mono or bis-pyridinium oximes along with anticholinergic and an anticonvulsant drugs are recommended for the treatment of OP poisoning. Unfortunately, the drawback of the existing reactivator is that owing to the permanent charge present on the pyridinium makes them inefficient to cross the blood-brain barrier (BBB) and reactivate OP-inhibited central nervous system (CNS) acetylcholinesterase. Therefore, there is a need of reactivator that could cross the BBB and reactivate the OP inhibited acetylcholinesterase. Objective: The objectives of the study were synthesis, molecular docking, BSA binding and in-vitro estimation of oximes of various substituted imidazo [1,2-a]pyridine against paraoxon inhibited acetylcholinesterase. Method: The reactivators were synthesized in three steps and characterized using various spectroscopic techniques. Molecular docking study was performed on 2WHP and 3ZLV PDB using Autodock tool. The acid dissociation constant (pKa) of oximes was calculated experimentally and drug-likeness properties of the oximes were calculated In silico using mole inspiration and Swiss ADME software. The binding of oximes with bovine serum albumin (BSA) was also investigated by UV-Vis spectrophotometer. The reactivation potential of the oximes was determined by in vitro enzymatic assay. Result: in-silico study inferred that synthesized molecules fulfilled the parameters that required for a successful CNS drug candidate. Further, in-vitro enzymatic assay indicated reasonable reactivation potential of the oximes against paraoxon-inhibited AChE. The binding of oximes with bovine serum albumin (BSA) revealed static quenching of intrinsic fluorescence of BSA by oxime. The binding constant value and number of binding sites were found 0.24 mol-1 and 1 respectively. Conclusion: The results of study concluded that this scaffold could be used for further designing of more efficient uncharged reactivators.
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- 2022
7. A multifaceted approach towards understanding the peculiar behavior of (α)-hydroxyiminophosphonates
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Jean-Christophe Monbaliu, Loïc Quinton, Thomas Toupy, Kristof Van Hecke, and Christopher Kune
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chemistry.chemical_compound ,Hydroxylamine ,chemistry ,Tandem ,Fragmentation (mass spectrometry) ,Stereochemistry ,Organic Chemistry ,Moiety ,Protonation ,Oxime ,High-performance liquid chromatography ,Phosphonate - Abstract
The peculiar isomer-selective reduction of (α)-hydroxyiminophosphonates (oxime isomers) into (α)-hydroxyaminophosphonate (hydroxylamine) derivatives is presented. A library of 16 (α)-hydroxyiminophosphonates is prepared and studied via a unique multifaceted approach involving the interplay of NMR, XRD, MS, IM-MS and computational chemistry techniques. The combination of NMR, XRD and HPLC enables the seamless separation, identification and quantification of the oxime isomers (E/Z). Tandem MS (MS/MS) enables the determination of the fragmentation patterns for both isomers. Collision energy breakdown curves highlight the order of apparition of the fragments as well as their related energy of fragmentation, demonstrating that the strength of the C–P bond in the Z isomers is much weaker than in the E isomers. Computational chemistry demonstrates that favorable protonation site is isomer-dependent with the phosphonate moiety being the favorable protonation site for the E isomers, while protonation occurs preferentially on the amino moiety for Z isomers regardless of the phosphite source. The combination of these various methods led an unprecedented level of characterization of oxime isomers, providing a better uderstanding of the isomer-dependent behavior of (α)-hydroxyiminophosphonates.
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- 2022
8. The toxicity of organophosphorus compounds can be reduced by cholinesterase activity
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Kovarik, Zrinka, Kolić, Dora, Čadež, Tena, and Maček Hrvat, Nikolina
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Organophosphorus compounds ,acetylcholinesterase ,oxime ,nerve agent ,reactivation - Abstract
The main action mechanism of organophosphorus compounds (OP) is the inhibition of acetylcholinesterase (AChE) that causes the accumulation of the neurotransmitter acetylcholine and excessive stimulation of nicotinic and muscarinic receptors in the central and peripheral nervous system, leading to the paralysis of cholinergic synaptic transmission. Although BChE is generally considered as having no natural physiological function, the most likely function for BChE is as backup for AChE and protection of synaptic AChE from man-made and naturally occurring poisons. Both enzymes should be reactivated by strong nucleophiles such as oximes to avoid severe health effects after exposure to OP. However, inhibition and reactivation of both enzymes are fine-tuning chemical processes that depend on the structure of all reactants. Therefore, we evaluated the inhibition of cholinesterase activity with selected OP-herbicides, insecticides and newly scheduled nerve agents as well as reactivation of OP-inhibited AChE and BChE with click chemistry-synthetized oximes. Although several oximes showed reasonable potency in reactivating AChE and BChE conjugated with methylphosphonates, phosphorates and phosphoramidates, a universally superior antidote was not identified. However, our results showed that toxicity of various OP can be reduced by efficient reactivation of phosphylated AChE and BChE. Our findings also offer a valuable and comprehensive platform for further development of antidotes and scavengers against tabun and related phosphoramidate exposures, such as the Novichok series of compounds. This research was supported by the Croatian Science Foundation (IP-2018-01-7683).
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- 2023
9. The OP Wars - A New Hope: effectiveness of novel oxime antidotes in organophosphate poisoning
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Kolić, Dora and Kovarik, Zrinka
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Organophosphorus compounds ,butyrylcholinesterase ,oxime ,bioscavenger - Abstract
Organophosphorus (OP) compounds were developed in Germany in the 1930s as pesticides and as warfare nerve agents (NA) since they were found to have a lethal effect on insects and mammals. Although 193 states signed the Chemical Weapons Convention in the 1997, which prohibits the production and use of NA, and they are slowly being replaced as pesticides by newer less hazardous formulations, OP compounds still pose a threat in terrorist attacks and they account for more than three million accidental or deliberate cases of poisoning a year worldwide [1]. OP exert their toxic effect primarily by inhibiting acetylcholinesterase (AChE), an essential enzyme for neurotransmitter acetylcholine (ACh) hydrolysis, and related enzyme butyrylcholinesterase (BChE). AChE inhibition leads to accumulation of ACh in the nerve system and overstimulation of cholinergic receptors in the entire body, which induces symptoms like nausea, convulsions, loss of consciousness, respiratory failure and ultimately death, while poisoning survivors additionally suffer from considerable irreversible neurological complications [2]. Emergency treatment of acute OP poisoning aims to recover the activity of the inhibited enzyme by pyridinium oxime reactivators that displace the phosphorus moiety bound within the enzyme catalytic site. Their disadvantages are that they generally weakly reactivate BChE, do not reactivate AChE in the brain due to their positive charge and the subsequent inability to cross the blood-brain barrier, and they are not universal reactivators of all NA and pesticides [3]. The goal of our study is to identify and kinetically characterize novel oxime antidotes which would efficiently reactivate BChE and potentially establish a pseudocatalytic scavenger system which could detoxify OP in the bloodstream before they reach target tissues [3]. Structurally various novel oximes were tested as reactivators of NA sarin-, cyclosarin-, VX- and tabun-inhibited human AChE and BChE, as well as chosen OP pesticides. For several oximes BChE reactivation potency was showed to be superior when compared to the standard oximes used in medical practice, and binding affinities of phosphylated BChE for some oximes increased up to 1900-fold compared to pyridinium oximes, establishing them as promising candidates for future treatment development.
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- 2023
10. Structural basis of binding and inhibition of ornithine decarboxylase by 1-amino-oxy-3-aminopropane
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Irving E. Vega, Bilal Aleiwi, Edmund Ellsworth, Kelly Suino-Powell, X. Edward Zhou, André S. Bachmann, Joseph S. Brunzelle, Chad R. Schultz, Jared Lamp, and Karsten Melcher
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genetic structures ,education ,Ornithine Decarboxylase ,Biochemistry ,Article ,Cofactor ,Ornithine decarboxylase ,chemistry.chemical_compound ,Protein Domains ,mental disorders ,Humans ,Molecular Biology ,Pyridoxal ,chemistry.chemical_classification ,Propylamines ,biology ,fungi ,Substrate (chemistry) ,Cell Biology ,Ornithine Decarboxylase Inhibitors ,Ornithine ,Oxime ,Enzyme ,chemistry ,Covalent bond ,biology.protein ,psychological phenomena and processes ,Protein Binding - Abstract
Ornithine decarboxylase (ODC) is the rate-limiting enzyme for the synthesis of polyamines (PAs). PAs are oncometabolites that are required for proliferation, and pharmaceutical ODC inhibition is pursued for the treatment of hyperproliferative diseases, including cancer and infectious diseases. The most potent ODC inhibitor is 1-amino-oxy-3-aminopropane (APA). A previous crystal structure of an ODC–APA complex indicated that APA non-covalently binds ODC and its cofactor pyridoxal 5-phosphate (PLP) and functions by competing with the ODC substrate ornithine for binding to the catalytic site. We have revisited the mechanism of APA binding and ODC inhibition through a new crystal structure of APA-bound ODC, which we solved at 2.49 Å resolution. The structure unambiguously shows the presence of a covalent oxime between APA and PLP in the catalytic site, which we confirmed in solution by mass spectrometry. The stable oxime makes extensive interactions with ODC but cannot be catabolized, explaining APA's high potency in ODC inhibition. In addition, we solved an ODC/PLP complex structure with citrate bound at the substrate-binding pocket. These two structures provide new structural scaffolds for developing more efficient pharmaceutical ODC inhibitors.
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- 2021
11. Iridium-Catalyzed Regioselective Hydroalkynylation of Internal Alkenes Directed by an Oxime
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Peng-Chao Gao, Bi-Jie Li, and Zi-Xuan Wang
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chemistry.chemical_classification ,Allylic rearrangement ,Alkene ,Organic Chemistry ,food and beverages ,Regioselectivity ,chemistry.chemical_element ,Alcohol ,Oxime ,Biochemistry ,Medicinal chemistry ,Catalysis ,chemistry.chemical_compound ,Alkynylation ,chemistry ,Iridium ,Physical and Theoretical Chemistry - Abstract
We report here an iridium-catalyzed hydroalkynylation of allylic alcohols protected by an oxime group. Catalytic alkynylation occurs exclusively at the distal position of the alkene. This method generates γ-alkynyl alcohol oximes directly from internal alkenes and terminal alkynes. The oxime group can be readily removed to afford a free alcohol, thus providing an indirect route for the catalytic hydroalkynylation of allylic alcohols.
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- 2021
12. Nickel-Catalyzed Enantioselective Desymmetrizing Aza-Heck Cyclization of Oxime Esters
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Liu-Zhu Gong, Hong-Cheng Shen, Heming Jiang, Yun-Dong Wu, Xinhao Zhang, Wen-Ao Li, Ying Chen, Wen-Qian Zhang, Ying Zhang, and Mostafa Sayed
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inorganic chemicals ,Nickel ,chemistry.chemical_compound ,Chemistry ,Enantioselective synthesis ,chemistry.chemical_element ,Organic chemistry ,General Chemistry ,Oxime ,Catalysis - Abstract
Densely functionalized chiral nitrogen-containing heterocycles are ubiquitous in bioactive synthetic compounds and natural products. Herein, we report a nickel (Ni)-catalyzed enantioselective desym...
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- 2021
13. Visible-Light Photoredox-Catalyzed Dicarbofunctionalization of Styrenes with Oxime Esters and CO2: Multicomponent Reactions toward Cyanocarboxylic Acids and γ-Keto Acids
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Cong Zhou, Junxue Bai, Jianwei Sun, Jiang Cheng, Song Sun, Yu Sha, and Miao Li
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chemistry.chemical_classification ,Cyclic ketone ,chemistry.chemical_compound ,Ketone ,chemistry ,Organic Chemistry ,Organic chemistry ,Physical and Theoretical Chemistry ,Oxime ,Biochemistry ,Catalysis ,Visible spectrum - Abstract
A photoredox-catalyzed dicarbofunctionalization of styrenes with oxime esters and CO2 has been achieved. Notably, a series of four-, five-, or six-membered cyclic ketone oximes worked well to furnish a wide range of e-, ζ-, and η-cyanocarboxylic acids in good yields. Furthermore, a series of γ-keto acids also could be obtained by employing acyclic ketone oxime esters as the carbonyl radical precursor. It provides convergent access to diverse biologically important cyanocarboxylic and γ-keto acids.
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- 2021
14. Synthesis and Anti-HCV Activities of 18β-Glycyrrhetinic Acid Derivatives and Their In-Silico ADMET Analysis
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Zhang Kaixia, Qian Xijing, Fei Chen, Peng-Ru Wang, Lin Jia, Xiao-Juan Liu, Yong-Sheng Jin, and Lin Li
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010405 organic chemistry ,In silico ,General Medicine ,Oxime ,Antiviral Agents ,01 natural sciences ,Combinatorial chemistry ,Triterpenes ,Terpenoid ,0104 chemical sciences ,Acylation ,Structure-Activity Relationship ,010404 medicinal & biomolecular chemistry ,chemistry.chemical_compound ,chemistry ,Drug Discovery ,Glycyrrhetinic Acid ,Molecular Medicine ,Glycyrrhizin ,IC50 ,Lead compound ,Active metabolite - Abstract
Background: Licorice is widely used as a hepatoprotective herb for thousands of years in Traditional Chinese Medicine, and its main chemical constituent glycyrrhizin (GL) is used as a treatment for chronic hepatitis in Japan for over 20 years. 18β-Glycyrrhetinic acid (GA) is the main active metabolite of GL. Objective: Series of GA derivatives were designed and synthesized, and their anti-HCV activities were screened to investigate structure-activity relationship (SAR). Besides, their in-silico ADMET properties were analyzed to search for promising lead compound for further identification of anti-HCV terpenoid candidate. Methods: GA derivatives were synthesized via reactions of oxidation, oxime, rearrangement, esterification and acylation, etc. In vitro anti-HCV activity of derivatives was tested on the HCV cell culture (HCVcc) system. In-silico ADMET properties analysis were performed via “pkCSM” and “SwissADME” platforms. Results: Eighteen GA derivatives were synthesized and their structures were confirmed by MS and NMR spectrums. All compounds exhibited superior HCV inhibitory activity to that of GA. Compound 2 possessed the most potent anti-HCV activity with IC50 value of 0.79 μM, which is nearly 58 times potent than SA (a previously reported potent anti-HCV terpenoids) and >200 times than GA. SAR revealed the introduction of 3-oxo, short-chain (C1-C3) aliphatic alcohols or cyclic aliphatic amines is conducive to improving anti-HCV activity. In-silico ADMET prediction demonstrated most of the potent compounds possessed favorable ADMET properties. Conclusion: Structural modification of GA at 3-position and 30-position is an effective approach to searching for potent anti-HCV agents. Compound 2, with the most potent anti-HCV activity and favorable in-silico ADMET properties, is a promising lead compound for further identification of anti-HCV terpenoid candidate.
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- 2021
15. On the mixed oxides-supported niobium catalyst towards benzylamine oxidation
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Javier Adrio, Gustavo S.G. de Carvalho, Alexandre A. Leitão, Álisson Silva Granato, Carla G. Fonseca, and Giovanni W. Amarante
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02 engineering and technology ,General Chemistry ,Nitroso ,010402 general chemistry ,021001 nanoscience & nanotechnology ,Oxime ,01 natural sciences ,Combinatorial chemistry ,Redox ,Catalysis ,0104 chemical sciences ,chemistry.chemical_compound ,Benzylamine ,chemistry ,Oxidizing agent ,0210 nano-technology ,Hydrogen peroxide ,Selectivity - Abstract
A series of mixed oxides-supported niobium-based catalysts has been synthesized and applied towards oxidation reactions of benzylamine derivatives. Under the optimized reaction conditions, the selectivity to oxime enhanced, leading to the main product with up to 72 %. Moreover, even α-substituted benzylamines were well tolerated and led to oximes in good isolated yields. It is important to mention; four equivalents of the harmless and inexpensive hydrogen peroxide were employed as oxidizing agent. Mechanism hypothesis suggested that the reaction proceed to selective benzylamine oxidation into nitroso intermediate, following by formation of the corresponding oxime tautomer mediated by an unstable water produced by NbOx supported catalyst. This consists the first mixed oxides-supported niobium-based catalyst for selective oxidation of benzylamines to oximes.
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- 2021
16. Highly Efficient Enrichment of O-GlcNAc Glycopeptides Based on Chemical Oxidation and Reversible Hydrazide Chemistry
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Mingliang Ye, Hongqiang Qin, Luyao Liu, Jiahua Zhou, Yao Chen, Yongzhan Nie, and Xuyang Yue
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chemistry.chemical_classification ,Crosstalk (biology) ,chemistry.chemical_compound ,chemistry ,Moiety ,RNA ,Hydrazide ,Oxime ,Glycoprotein ,Aldehyde ,Combinatorial chemistry ,Glycopeptide ,Analytical Chemistry - Abstract
Protein O-GlcNAcylation has been implicated in a broad range of cellular processes, while the functional research is still lagging behind other post-translational modification (PTMs), as a result of the low stoichiometry and limited enrichment efficiency. Herein, a strategy, named CHO-GlcNAc, was developed for O-GlcNAc glycopeptide enrichment. In this strategy, the O-GlcNAc glycopeptides were first enzymatically labeled with a Gal moiety, followed by chemical oxidation to efficiently introduce the aldehyde groups. The labeled O-GlcNAc glycopeptides could be efficiently enriched based on the equilibrium between the hydrazine and oxime bonds. Good specificity of the glycopeptide enrichment was observed from the mixtures of glycopeptide and non-glycopeptides using the CHO-GlcNAc method. Then, it was applied to analyze O-GlcNAcylation in the nucleus of HeLa cells, and 829 potential O-GlcNAcylation sites on 274 glycoproteins were identified, including the two readers of m6A (YTHDF1 and YTHDF3), which could provide clues for the mechanism of crosstalk between O-GlcNAcylation and other PTMs of proteins and RNA. Thus, this method could be a versatile tool for the proteomic analysis of O-GlcNAcylation.
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- 2021
17. In vitro studies of hypoxia inducible factor‐prolyl hydroxylase inhibitors daprodustat, desidustat, and vadadustat for equine doping control
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Tajudheen K. Karatt, Michael Benedict Subhahar, Zubair Perwad, Abdul Khader Karakka Kal, Binoy Mathew, and Moses Philip
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Doping in Sports ,chemistry.chemical_classification ,Glycine ,Pharmaceutical Science ,Prolyl-Hydroxylase Inhibitors ,Quinolones ,Sulfonic acid ,Oxime ,Glucuronic acid ,In vitro ,Analytical Chemistry ,chemistry.chemical_compound ,Hydrolysis ,chemistry ,Hypoxia-inducible factors ,Biochemistry ,Barbiturates ,Animals ,Environmental Chemistry ,Horses ,Hypoxia ,Picolinic Acids ,Spectroscopy ,Conjugate - Abstract
Performance-enhancing substances and methods have become a serious problem in competitive sports. The hypoxia-inducible factor (HIF) stabilizers can enhance the organism's capacity for molecular oxygen transport and are likely to be abused as performance-enhancing agents in sports. This paper describes the metabolic conversion of the popular hypoxia inducible factor-prolyl hydroxylase (HIF-PH) inhibitors, namely, daprodustat, desidustat, and vadadustat using equine liver microsomes, determined on a QExactive high-resolution mass spectrometer. During this study, a total of 10 metabolites for daprodustat (all are Phase I), 10 metabolites for desidustat (five each for Phase I and Phase II), and 15 metabolites for vadadustat (six for Phase I and nine for Phase II) were detected. The important findings of the current research are as follows: (1) All the three HIF-PH inhibitor drug candidates are prone to oxidation, which results in corresponding hydroxylated metabolites; (2) in desidustat, hydrolysis and dissociation of oxime linkage also observed; (3) the glucuronic acid conjugate (except daprodustat) of the parent drugs as well as the monohydroxylated analogs were observed; (4) sulfonic acid conjugated metabolites were observed only for vadadustat.
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- 2021
18. Moisture-resistant and highly adhesive acrylate-based sealing materials embedded with oxime-based photoinitiators for hermetic optical devices
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Jin-Wook Choi, Jisung Park, Seung-Rak Son, Jun Hyup Lee, Chan Beom Park, Jongil An, and Soyern Kim
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Acrylate ,Fabrication ,Materials science ,General Chemical Engineering ,General Chemistry ,Oxime ,Catalysis ,chemistry.chemical_compound ,Chemical engineering ,chemistry ,UV curing ,Adhesive ,Photoinitiator ,Chemical decomposition - Abstract
The hermetic sealing of optoelectronic devices has attracted much attention because it can endow the devices with long-term operation reliability and high mechanical resistance. Herein, we present a facile and efficacious strategy for fabrication of water-resistant and highly adhesive acrylate-based sealing materials for hermetic optical devices using oxime-based photoinitiators. Compared with conventional sealing materials containing ketone-based photoinitiator, those embedded with oxime-based photointiators afforded a strong UV absorption in the effective wavelength range, a high UV curing conversion of 99.5% at a low radiant energy of 1.0 J cm−2, a remarkable adhesion strength of 42.2 kgf cm−2, an improved water impermeability of 5.3 g m−2 day−1, and a reduced internal pollution length of 104.9 µm. These excellent properties of the fabricated sealing materials are attributed to the fragmentation mechanism of oxime-based photoinitiators which can generate numerous initiating radicals through multi-step decomposition reactions, resulting in the efficient initiation for photoreaction with acrylate resins. This study provides promising sealing materials based on the oxime-based photoinitiators for ultra-slim and flexible optoelectronic applications.
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- 2021
19. Remote C−H Pyridylation of Hydroxamates through Direct Photoexcitation of O ‐Aryl Oxime Pyridinium Intermediates
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Sungwoo Hong, Byeongseok Kweon, Changha Kim, and Seonyul Kim
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Reaction mechanism ,Aryl ,Radical ,General Chemistry ,General Medicine ,Oxime ,Combinatorial chemistry ,Catalysis ,chemistry.chemical_compound ,chemistry ,Functional group ,Electronic effect ,Pyridinium ,Bond cleavage - Abstract
Herein, we report an efficient strategy for the remote C-H pyridylation of hydroxamates with excellent ortho-selectivity by designing a new class of photon-absorbing O-aryl oxime pyridinium salts generated in situ from the corresponding pyridines and hydroxamates. When irradiated by visible light, the photoexcitation of oxime pyridinium intermediates generates iminyl radicals via the photolytic N-O bond cleavage, which does not require an external photocatalyst. The efficiency of light absorption and N-O bond cleavage of the oxime pyridinium salts can be modulated through the electronic effect of substitution on the O-aryl ring. The resultant iminyl radicals enable the installation of pyridyl rings at the γ-CN position, which yields synthetically valuable C2-substituted pyridyl derivatives. This novel synthetic approach provides significant advantages in terms of both efficiency and simplicity and exhibits broad functional group tolerance in complex settings under mild and metal-free conditions.
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- 2021
20. An Inhibitor-in-Pieces Approach to DAHP Synthase Inhibition: Potent Enzyme and Bacterial Growth Inhibition
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Robert Szabla, Paul J. Berti, Christopher M. Brown, Murray S. Junop, Pallavi Mukherjee, Maren Heimhalt, Rebecca Turner, and Ryan A. Grainger
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Stereochemistry ,DAHP synthase ,010402 general chemistry ,01 natural sciences ,Phosphates ,03 medical and health sciences ,chemistry.chemical_compound ,Catalytic Domain ,Escherichia coli ,Aromatic amino acids ,Shikimate pathway ,3-Deoxy-7-Phosphoheptulonate Synthase ,030304 developmental biology ,chemistry.chemical_classification ,0303 health sciences ,biology ,ATP synthase ,Chemistry ,Active site ,Oxime ,0104 chemical sciences ,Kinetics ,Infectious Diseases ,Enzyme ,biology.protein ,Growth inhibition - Abstract
3-Deoxy-d-arabinoheptulosonate-7-phosphate (DAHP) synthase catalyzes the first step in the shikimate biosynthetic pathway and is an antimicrobial target. We used an inhibitor-in-pieces approach, based on the previously reported inhibitor DAHP oxime, to screen inhibitor fragments in the presence and absence of glycerol 3-phosphate to occupy the distal end of the active site. This led to DAHP hydrazone, the most potent inhibitor to date, Ki = 10 ± 1 nM. Three trifluoropyruvate (TFP)-based inhibitor fragments were efficient inhibitors with ligand efficiencies of up to 0.7 kcal mol-1/atom compared with 0.2 kcal mol-1/atom for a typical good inhibitor. The crystal structures showed the TFP-based inhibitors binding upside down in the active site relative to DAHP oxime, providing new avenues for inhibitor development. The ethyl esters of TFP oxime and TFP semicarbazone prevented E. coli growth in culture with IC50 = 0.21 ± 0.01 and 0.77 ± 0.08 mg mL-1, respectively. Overexpressing DAHP synthase relieved growth inhibition, demonstrating that DAHP synthase was the target. Growth inhibition occurred in media containing aromatic amino acids, suggesting that growth inhibition was due to depletion of some other product(s) of the shikimate pathway, possibly folate.
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- 2021
21. Chemoenzymatic one-pot reaction from carboxylic acid to nitrile via oxime†
- Author
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Miroslav Pátek, Victoria Weilch, Robert Rädisch, Ludmila Martínková, Sebastian Hecko, Margit Winkler, Melissa Horvat, Florian Rudroff, Astrid Schiefer, Norbert Klempier, and Birgit Wilding
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chemistry.chemical_classification ,chemistry.chemical_compound ,Chemistry ,Nitrile ,One pot reaction ,Carboxylic acid ,Organic chemistry ,Oxime ,Catalysis - Abstract
We report a new chemoenzymatic cascade starting with aldehyde synthesis by carboxylic acid reductase (CAR) followed by chemical in situ oxime formation. The final step to the nitrile is catalyzed by aldoxime dehydratase (Oxd). Full conversions of phenylacetic acid and hexanoic acid were achieved in a two-phase mode., We report a new chemoenzymatic cascade starting with aldehyde synthesis by carboxylic acid reductase (CAR) followed by chemical in situ oxime formation and enzymatic dehydration by aldoxime dehydratase (Oxd).
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- 2021
22. Effect of the Steric Hindrance and Branched Substituents on Visible Phenylamine Oxime Ester Photoinitiators: Photopolymerization Kinetics Investigation through Photo‐DSC Experiments
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Zhong-Han Lee, Tung-Liang Huang, Bernadette Graff, Akram Hijazi, Jacques Lalevée, Ching-Chin Chen, Yung-Chung Chen, and Fatima Hammoud
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chemistry.chemical_classification ,Steric effects ,Thermogravimetric analysis ,Aniline Compounds ,Calorimetry, Differential Scanning ,Light ,Esters ,General Medicine ,Oxime ,Photochemistry ,Biochemistry ,chemistry.chemical_compound ,Differential scanning calorimetry ,Photopolymer ,chemistry ,Oximes ,Physical and Theoretical Chemistry ,Photoinitiator ,Alkyl ,Methyl group - Abstract
In this work, free radical photopolymerization (FRP) kinetics for series of different phenylamine oxime ester structures (DMA-P, DEA-P, DMA-M, TP-2P, TP-2M and TP-3M) was investigated. Steric hindrance and branched substituents were prepared to realize the corresponding electronic and photopolymerization effects. The photophysical, electrochemical, thermal properties and radical concentration were investigated by UV-visible spectroscopy, cyclic voltammetry (CV), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC) and electron paramagnetic resonance (EPR). Furthermore, the structure-reactivity relationships were also studied in detail through photo-DSC experiment. We demonstrate that the introduction of alkyl chains and/or numbers of oxime esters affects significantly the photoreactivity. Under the same weight ratio of formulation and irradiated condition, TP-3M containing three oxime esters in its structure and methyl group in the periphery exhibits the highest double-bond conversion efficiency. TP-3M-based formulation also shows a wide operation window under different contents and light intensities. Importantly, the photoreactivity of the TP-3M-based system was found to be better than the commercial photoinitiator (OXE-01) under LED@405 nm at a low concentration. This work could provide some significance to the design of oxime esters with enhanced photoreactivity.
- Published
- 2021
23. Synthesis and crystal structure of a new chiral α-aminooxime nickel(II) complex
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Isabelle Suisse, Mathieu Sauthier, A. Dahdouh, P. Loxq, Y. Homrani, Frédéric Capet, El Amrani, Université Abdelmalek Essaâdi (UAE), Unité de Catalyse et Chimie du Solide - UMR 8181 (UCCS), and Université d'Artois (UA)-Centrale Lille-Institut de Chimie du CNRS (INC)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)
- Subjects
inorganic chemicals ,crystal structure ,chemistry.chemical_element ,Crystal structure ,Research Communications ,Crystal ,chemistry.chemical_compound ,nickel ,otorhinolaryngologic diseases ,α-aminooxime ,General Materials Science ,Chelation ,alpha-aminooxime ,Crystallography ,Hydrogen bond ,Ligand ,α-aminooxime ,General Chemistry ,[CHIM.CATA]Chemical Sciences/Catalysis ,Condensed Matter Physics ,Oxime ,Nickel ,chemistry ,QD901-999 ,(r)-limonene ,Monoclinic crystal system - Abstract
The reaction of a nickel precursor with an enantiomerically pure amino-oxime issued from (R)-limonene led to the formation of bis[κ3 N,N,N-(aminooxime)-μ-chlorido]dichlorodinickel as a new dinuclear nickel complex., A dinuclear nickel complex with (S)-limonene based aminooxime ligand has been isolated and its crystal structure determined. The resolved structure of dichloridobis{(2S,5R)-2-methyl-5-(prop-1-en-2-yl)-2-[(pyridin-2-yl)methylamino]cyclohexan-1-one oxime}dinickel(II), [Ni2Cl2(C16H23ClN3O)2], at 100 K has monoclinic (P21) symmetry. The two NiII ions in the dinuclear complex are each coordinated in a distorted octahedral environment by three nitrogen atoms, a terminal chloride and two μ bridging chlorides. Each oxime ligand is coordinated to nickel(II) by the three nitrogen atoms, leading to two five-membered chelate rings, each displaying an envelope conformation. In the crystal, numerous intermolecular and intramolecular hydrogen bonds lead to the formation of a three-dimensional network structure.
- Published
- 2021
24. The Origin of Stereoselectivity in the Hydrogenation of Oximes Catalyzed by Iridium Complexes: A DFT Mechanistic Study
- Author
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Qaim Ali, Yongyong Chen, Ruixue Zhang, Zhewei Li, Yanhui Tang, Min Pu, and Ming Lei
- Subjects
DFT ,non-covalent interactions ,stereoselectivity ,asymmetric hydrogenation ,oxime ,Chemistry (miscellaneous) ,Organic Chemistry ,Drug Discovery ,Molecular Medicine ,Pharmaceutical Science ,Physical and Theoretical Chemistry ,Analytical Chemistry - Abstract
Herein the reaction mechanism and the origin of stereoselectivity of asymmetric hydrogenation of oximes to hydroxylamines catalyzed by the cyclometalated iridium (III) complexes with chiral substituted single cyclopentadienyl ligands (Ir catalysts A1 and B1) under acidic condition were unveiled using DFT calculations. The catalytic cycle for this reaction consists of the dihydrogen activation step and the hydride transfer step. The calculated results indicate that the hydride transfer step is the chirality-determining step and the involvement of methanesulfonate anion (MsO−) in this reaction is of importance in the asymmetric hydrogenation of oximes catalyzed by A1 and B1. The calculated energy barriers for the hydride transfer steps without an MsO− anion are higher than those with an MsO− anion. The differences in Gibbs free energies between TSA5−1fR/TSA5−1fS and TSB5−1fR/TSB5−1fS are 13.8/13.2 (ΔΔG‡ = 0.6 kcal/mol) and 7.5/5.6 (ΔΔG‡ = 1.9 kcal/mol) kcal/mol for the hydride transfer step of substrate protonated oximes with E configuration (E−2a−H+) with MsO− anion to chiral hydroxylamines product R−3a/S−3a catalyzed by A1 and B1, respectively. According to the Curtin–Hammet principle, the major products are hydroxylamines S−3a for the reaction catalyzed by A1 and B1, which agrees well with the experimental results. This is due to the non-covalent interactions among the protonated substrate, MsO− anion and catalytic species. The hydrogen bond could not only stabilize the catalytic species, but also change the preference of stereoselectivity of this reaction.
- Published
- 2022
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25. Computational Investigation of the Formation of Substituted Isoindole N-Oxides through the Photo-oxidative Cyclization of 2′-Alkynylacetophenone Oximes
- Author
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My Tien Pham, Anh Nguyen, Andrew S. Petit, Danielle Torres, and Thao Tran
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chemistry.chemical_compound ,chemistry ,Radical ion ,Organic Chemistry ,Substituent ,Density functional theory ,Isoquinoline ,Oxime ,Ring (chemistry) ,Isoindole ,Medicinal chemistry ,Isopropyl - Abstract
Our recently published joint experiment-theory study of the photo-oxidative intramolecular cyclization of 2'-alkynylacetophenone oximes, performed in collaboration with the de Lijser group, presented the first reported formation of isoindole N-oxides. That study focused on determining a mechanistic explanation for the unexpected chemistry observed when three 2'-alkynylacetophenone oximes were photo-oxidized with 9,10-dicyanoanthracene (DCA), specifically the derivatives with a phenyl, isopropyl, or n-butyl substituent at the alkynyl group. Here, we use density functional theory to develop a broader understanding of the scope of this chemistry. In particular, we demonstrate that substituents on the alkynyl group and on the central benzene ring can significantly modulate the thermodynamic driving force for oxime radical cation generation when DCA is used as the photosensitizer. In contrast, substituents are shown to have a small impact on the chemical reactivity of the radical cation intermediates. In particular, 5-exo radical cation cyclization, which ultimately results in an isoindole N-oxide product, is always kinetically and sometimes also thermodynamically preferred over 6-endo radical cation cyclization, which would produce an isoquinoline N-oxide product. Overall, this study provides mechanistic insights into the diversity of isoindole N-oxides that can be produced through the photo-oxidative cyclization of 2'-alkynylacetophenone oximes.
- Published
- 2021
26. Visible-Light-Induced Multicomponent Cascade Cycloaddition of N-Propargyl Aromatic Amines, Cyclobutanone Oxime Esters, and K2S2O5: Access to Cyanoalkylsulfonylated Quinolines
- Author
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Man Zhang, Qiankun Xu, Kaimo Kuang, Nengneng Zhou, Ziqin Xia, and Sixin Wu
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chemistry.chemical_compound ,chemistry ,Cascade ,Organic Chemistry ,Functional group ,Aromatization ,Substrate (chemistry) ,Cyclobutanone ,Oxime ,Combinatorial chemistry ,Cycloaddition ,Visible spectrum - Abstract
A visible-light-induced cascade cyanoalkylsulfonylation/cyclization/aromatization of N-propargyl aromatic amines with K2S2O5 and cyclobutanone oxime esters for the construction of cyanoalkylsulfonylated quinolines is developed. This cascade transformation features mild reaction conditions, a broad substrate scope, and excellent functional group compatibility, providing a convenient route toward cyanoalkylsulfonylated quinolines via the formation of a C-C bond and two C-S bonds in one step.
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- 2021
27. <scp>Palladium‐Catalyzed</scp> Sequential Cyclization/Functionalization of Oxime Ethers with Unactivated Vinyl Ethers for Tunable Assembly of Structurally Diverse Isoxazoles
- Author
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Zidong Lin, Wanqing Wu, Dan He, Jianxiao Li, and Huanfeng Jiang
- Subjects
chemistry.chemical_compound ,Annulation ,chemistry ,medicine ,Surface modification ,chemistry.chemical_element ,Organic chemistry ,General Chemistry ,Vinyl ether ,Oxime ,medicine.drug ,Palladium ,Catalysis - Published
- 2021
28. Chemodivergent Synthesis of Oxazoles and Oxime Ethers Initiated by Selective C–N/C–O Formation of Oximes and Diazo Esters
- Author
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Shaozhong Wang and Zhenjie Qi
- Subjects
chemistry.chemical_classification ,Annulation ,Ketone ,Organic Chemistry ,Alkyne ,Ether ,Oxime ,Biochemistry ,Medicinal chemistry ,Aldehyde ,chemistry.chemical_compound ,chemistry ,Amide ,Diazo ,Physical and Theoretical Chemistry - Abstract
Chemodivergent reactions of oximes and diazo esters involving Rh-catalyzed [3+2] annulation and photodriven O-H insertion have been developed to generate oxazoles and oxime ethers. A range of aldehyde and ketone oximes reacted with α-diazocarbonyl compounds in a controllable manner in which functional groups, including ketone, ester, amide, ether, thiol ether, silane, alkene, allene, and alkyne groups, were well tolerated.
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- 2021
29. Caged Oxime Reactivators Designed for the Light Control of Acetylcholinesterase Reactivation †
- Author
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Seok-Ki Choi, Shengzhuang Tang, and Jayme Cannon
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chemistry.chemical_classification ,Cholinesterase Reactivators ,Organophosphate ,General Medicine ,Coumarin ,Oxime ,Biochemistry ,Acetylcholinesterase ,Paraoxon ,chemistry.chemical_compound ,Enzyme ,chemistry ,Oximes ,Ultraviolet light ,Cholinergic ,Cholinesterase Inhibitors ,Physical and Theoretical Chemistry ,Acetamide - Abstract
Despite its promising role in the active control of biological functions by light, photocaging remains untested in acetylcholinesterase (AChE), a key enzyme in the cholinergic family. Here, we describe synthesis, photochemical properties and biochemical activities of two caged oxime compounds applied in the photocontrolled reactivation of the AChE inactivated by reactive organophosphate. Each of these consists of a photocleavable coumarin cage tethered to a known oxime reactivator for AChE that belongs in an either 2-(hydroxyimino)acetamide or pyridiniumaldoxime class. Of these, the first caged compound was able to successfully go through oxime uncaging upon irradiation at long-wavelength ultraviolet light (365 nm) or visible light (420 nm). It was further evaluated in AChE assays in vitro under variable light conditions to define its activity in the photocontrolled reactivation of paraoxon-inactivated AChE. This assay result showed its lack of activity in the dark but its induction of activity under light conditions only. In summary, this article reports a first class of light-activatable modulators for AChE and it offers assay methods and novel insights that help to achieve an effective design of caged compounds in the enzyme control.
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- 2021
30. Thermochemical Properties of Polyethylenoxime
- Author
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O. N. Golodkov, A. V. Markin, N. N. Smirnova, P. E. Goryunova, D. V. Anokhin, A. V. Knyazev, and N.V. Abarbanel
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chemistry.chemical_classification ,Range (particle radiation) ,chemistry.chemical_compound ,Materials science ,chemistry ,Thermodynamics ,Polymer ,Calorimetry ,Physical and Theoretical Chemistry ,Polyethylene ,Combustion ,Oxime ,Standard enthalpy of formation - Abstract
The energy of combustion of polyethylene oxime is determined for the first time via combustion calorimetry. The resulting experimental data are used to calculate the standard enthalpy of combustion and thermochemical characteristics of the formation of a partially crystalline polymer at T = 298.15 K, along with the thermodynamic characteristics of its synthesis in the range of 298.15–400 K.
- Published
- 2021
31. Radical–anion coupling through reagent design: hydroxylation of aryl halides†
- Author
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Andrew J. Greener, Ivan Ocaña, Victor Chechik, Will Owens-Ward, Michael J. James, Patrycja Ubysz, George Smith, and Adrian C. Whitwood
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Aryl ,Radical ,Halide ,General Chemistry ,Oxime ,Combinatorial chemistry ,Ion ,Hydroxylation ,chemistry.chemical_compound ,Chemistry ,chemistry ,Reagent ,Phenols - Abstract
The design and development of an oxime-based hydroxylation reagent, which can chemoselectively convert aryl halides (X = F, Cl, Br, I) into phenols under operationally simple, transition-metal-free conditions is described. Key to the success of this approach was the identification of a reducing oxime anion which can interact and couple with open-shell aryl radicals. Experimental and computational studies support the proposed radical-nucleophilic substitution chain mechanism., The design and development of an oxime-based hydroxylation reagent, which can chemoselectively convert aryl halides (X = F, Cl, Br, I) into phenols under operationally simple, transition-metal-free conditions is described.
- Published
- 2021
32. Preparation, Properties and Crystal Structure of syn-Isomer of 2,6-Dichlorophenyl-cyanoxime, H(2,6-diCl-PhCO): Potent Carbonyl Reductase Inhibitor
- Author
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Henry A. Charlier, Nikolay Gerasimchuk, Oleksandr Hietsoi, Seth Adu Amankrah, and Sergiy Tyukhtenko
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chemistry.chemical_compound ,Crystallography ,chemistry ,Nitrile ,Diastereomer ,Phenyl group ,Ether ,General Chemistry ,Crystal structure ,Condensed Matter Physics ,Oxime ,Acetonitrile ,Monoclinic crystal system - Abstract
The oximino(2,6-dichlorophenyl)acetonitrile, H(2,6-diCl-PhCO) has been synthesized in a reasonably high yield of 60%, and characterized using a variety of physical, electrochemical, spectroscopic methods and X-ray analysis. This compound belongs to the family of cyanoximes; a new subclass of oximes with the general formula NC–C(=N–OH)–R (where R is an electron-withdrawing group) which recently emerged as new biologically active compounds. This cyanoxime represents a disubstituted arylcyanoxime that was found to be a powerful inhibitor of the Carbonyl Reductase enzyme involved in the developing of resistance to anticancer treatment, and the making of cardiotoxic derivatives of anthracyclines that are currently used in medicine. The oximino(2,6-dichlorophenyl)acetonitrile, H(2,6-diCl-PhCO) is a weak acid with pKa = 6.17 and does not dissociate in organic polar protic and aprotic solvents. The cyanoxime was obtained as a microcrystalline mixture of two diastereomers (anti- and syn-) and deprotonates in solutions with the formation of yellow anions which exhibit solvatochromic behavior. However, one specific diastereomer—syn—was isolated in crystalline form from a solvent system as colorless blocks overlayed with pentane ether solution in a monoclinic system in a P2/c (#13) space group with unit cell parameters: a = 8.1720(2), b = 8.8013(3), c = 13.0146(4) and β = 102.546(3); Z = 4. A single crystal was studied using filtered CuKa radiation, providing Rint value of 0.0348 from a full-sphere of reflections. A crystal structure was solved using direct methods, and well refined to R1 = 0.0459, wR2 = 0.1268 and GOF = 1.107. The studied specimen of oximino(2,6-dichlorophenyl)acetonitrile, H(2,6-diCl-PhCO), represents a highly non-planar, rare syn-diastereomer in which the oxime fragment is positioned towards the chlorinated phenyl group. In the crystal, the compound forms a columnar structure extended along the c-direction by using slipped π–π stacking interactions. Columns are interconnected via H-bonding between the oxime OH-group and N atom of the nitrile group with the following parameters: N–H = 1.841 A, and 169.20° N···H–O angle. No thermal interconversion of syn- into anti- diastereomer was observed upon heating of crystals of one isomer under flow of Ar.
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- 2021
33. Visible-Light-Induced Transition-Metal-Free Nitrogen-Centered Radical Strategy for the Synthesis of 2-Acylated 9H-Pyrrolo[1,2-a]indoles
- Author
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Zan Chen, Bi-Quan Xiong, Jun Xie, Wen-Qin Yu, Kewen Tang, and Yu Liu
- Subjects
chemistry.chemical_classification ,Aryl ,Radical ,Organic Chemistry ,Triple bond ,Oxime ,Medicinal chemistry ,Acylation ,chemistry.chemical_compound ,chemistry ,Transition metal ,lipids (amino acids, peptides, and proteins) ,Isomerization ,Alkyl - Abstract
A convenient and efficient visible-light-induced tandem acylation/cyclization of N-propargylindoles with aryl- or alkyl-substituted acyl oxime esters for the synthesis of 2-acyl-substituted 9H-pyrrolo[1,2-a]indoles under transition-metal-free conditions, which proceeds via nitrogen-centered radical-mediated cleavage of the C-C σ-bond in acyl oxime esters, is established. The aryl or alkyl acyl radicals, which come from acyl oxime esters, attack the C-C triple bonds in N-propargylindoles and then go through intramolecular cyclization/isomerization.
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- 2021
34. Copper-Catalyzed Regioselective 1,4-Selenosulfonylation of 1,3-Enynes to Access Cyanoalkylsulfonylated Allenes
- Author
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Ling-Hui Zeng, Ping Bao, Wei-Ping Deng, Jie Wu, Feiyan Yu, and Fu-Sheng He
- Subjects
Chemistry ,Organic Chemistry ,Substrate (chemistry) ,Regioselectivity ,Oxime ,Biochemistry ,Combinatorial chemistry ,Catalysis ,chemistry.chemical_compound ,Functional group ,Copper catalyzed ,Surface modification ,Molecule ,Physical and Theoretical Chemistry - Abstract
By employing CuOAc as the catalyst, we realize a four-component reaction of 1,3-enynes, diselenides, DABCO·(SO2)2, and cycloketone oxime esters, providing facile access to diverse cyanoalkylsulfonylated allenyl selenides in moderate to good yields. This reaction features high functional group tolerance and a broad substrate scope, enabling the regioselective, sequential formation of C-SO2 and C-Se bonds under mild reaction conditions. Moreover, the utility of this methodology is further illustrated through the late-stage functionalization of drug-based molecules.
- Published
- 2021
35. Self-Healable and Reprocessable Cross-Linked Poly(urea-urethane) Elastomers with High Mechanical Performance Based on Dynamic Oxime–Carbamate Bonds
- Author
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Haonan Li, Yuhang Wang, Yingchao Cai, Yumin Yang, Chunmei Li, and Qiuyu Zhang
- Subjects
chemistry.chemical_compound ,Carbamate ,Materials science ,chemistry ,General Chemical Engineering ,medicine.medical_treatment ,Polymer chemistry ,Urea ,medicine ,General Chemistry ,Oxime ,Elastomer ,Industrial and Manufacturing Engineering - Published
- 2021
36. A New Dioxazolone for the Synthesis of 1,2‐Aminoalcohols via Iridium(III)‐Catalyzed C(sp 3 )−H Amidation
- Author
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Kevin Antien, Andrea Geraci, Michael Parmentier, and Olivier Baudoin
- Subjects
amidation ,dioxazolone ,chemistry.chemical_element ,General Medicine ,General Chemistry ,iridium ,1,2-amino alcohol ,Cleavage (embryo) ,Oxime ,Medicinal chemistry ,Catalysis ,chemistry.chemical_compound ,Hydrolysis ,chemistry ,Reagent ,Amide ,Reactivity (chemistry) ,Iridium ,C−H Activation ,Research Articles ,Research Article - Abstract
Vicinal aminoalcohols are widespread structural motifs in bioactive molecules. We report the development of a new dioxazolone reagent containing a p‐nitrophenyldifluoromethyl group, which 1. displays a good safety profile; 2. shows a remarkably high reactivity in the oxime‐directed iridium(III)‐catalyzed amidation of unactivated C(sp3)−H bonds; 3. leads to amide products which can be hydrolyzed under mild conditions. The amidation reaction is mild, general and compatible with both primary C−H bonds of tertiary and secondary alcohols, as well as secondary C−H bonds of cyclic secondary alcohols. This method provides an easy access to free 1,2‐aminoalcohols after efficient and mild cleavage of the oxime directing group and activated amide., A safe and bench‐stable dioxazolone reagent was developed for the oxime‐directed iridium(III)‐catalyzed amidation of unactivated C(sp3)−H bonds in tertiary and secondary alcohol‐based substrates. The amidation reaction is mild, general and compatible with both primary and secondary C−H bonds.
- Published
- 2021
37. Synthesis of O6-alkylated preQ1 derivatives
- Author
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Laurin Flemmich, Ronald Micura, and Sarah Moreno
- Subjects
Riboswitch ,heterocycles ,pyrrolopyrimidines ,Chemistry ,RNA methylation ,Science ,Organic Chemistry ,Substituent ,Queuosine ,Sequence (biology) ,Alkylation ,Oxime ,Combinatorial chemistry ,Full Research Paper ,deazapurines ,RNA cofactors ,chemistry.chemical_compound ,QD241-441 ,queuosine ,Methyl group - Abstract
A naturally occurring riboswitch can utilize 7-aminomethyl-O6-methyl-7-deazaguanine (m6preQ1) as cofactor for methyl group transfer resulting in cytosine methylation. This recently discovered riboswitch-ribozyme activity opens new avenues for the development of RNA labeling tools based on tailored O6-alkylated preQ1 derivatives. Here, we report a robust synthesis for this class of pyrrolo[2,3-d]pyrimidines starting from readily accessible N2-pivaloyl-protected 6-chloro-7-cyano-7-deazaguanine. Substitution of the 6-chloro atom with the alcoholate of interest proceeds straightforward. The transformation of the 7-cyano substituent into the required aminomethyl group turned out to be challenging and was solved by a hydration reaction sequence on a well-soluble dimethoxytritylated precursor via in situ oxime formation. The synthetic path now provides a solid foundation to access O6-alkylated 7-aminomethyl-7-deazaguanines for the development of RNA labeling tools based on the preQ1 class-I riboswitch scaffold.
- Published
- 2021
38. Design, Synthesis, and Antimicrobial Activity of (E)-4-Phenyl-2H-chromene-3-carbaldehyde O-[(1-Phenyl-1H-1,2,3-triazol-4-yl)methyl]oxime Derivatives
- Author
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J. Rao Yerrabelly, P. Rao Chittneni, R. Dasari, and Gangadhar Thalari
- Subjects
chemistry.chemical_compound ,chemistry ,Docking (molecular) ,Stereochemistry ,Ligand ,Lanosterol ,Organic Chemistry ,Click chemistry ,Protein Data Bank (RCSB PDB) ,Antimicrobial ,Oxime ,Antibacterial activity - Abstract
A new series of 1,4-disubstituted 1,2,3-triazole derivatives tethered to a 2H-chromene scaffold have been synthesized via a click reaction. The synthesized chromene–triazole conjugates were screened for their antibacterial activity against E. coli, S. aureus, P. aeruginosa and B. subtilis, as well as for antifungal activity against A. niger and C. albicans. Among the 17 synthesized compounds, 6 derivatives showed the best antimicrobial activity. Molecular docking studies of the title compounds with carotenoid dehydrosqualene synthase (PDB: 2ZCS) revealed docking scores within the range 98.241–91.488 against 106.573 for the reference ligand Ciprofloxacin and with lanosterol 14α-demethylase (CYP51; PDB ID: 5V5Z), 103.672–96.917 against 110.839 for the reference ligand Voriconazole.
- Published
- 2021
39. Copper-Catalyzed Electrophilic Amination of Diarylcadmium Reagents Utilizing Acetone O-(4- chlorophenylsulphonyl)oxime and Acetone O-(2-naphthylsulphonyl)oxime as Amination Agent
- Author
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Adem Korkmaz
- Subjects
chemistry.chemical_compound ,Fen ,Chemistry ,Science ,Electrophilic amination ,Reagent ,Electrophilic amination,diarylcadmium reagents,benzamides,ketoximes,coppercatalysis,coppercatalysis ,Copper catalyzed ,Acetone ,Organic chemistry ,Oxime ,Amination - Abstract
In this study, a CuCN catalyzed process of the diarylcadmium compounds by electrophilic amination method was developed using novel acetone O-(4-chlorophenylsulfonyl)oxime and acetone O-(2-naphthylsulfonyl)oxime. Herein, it has been demonstrated that primary arylamines can easily be obtained with good yields at room temperature by CuCN catalyzed amination of diarylcadmium reagents. It was settled down that the yield of primary arylamines depended strongly on the steric and electronic effects of organocadmium reagent and amination agent. In both amination reagents, meta-substituted arylamines were obtained in higher yields than para-substituted aryl amines. All reactions involving organocadmiums were carried out under an argon atmosphere by standard syringe/cannula methods. Amines as reaction products were separated from the reaction mixture as benzamide derivatives and purified and melting points, 1H NMR analysis determined their accuracy.
- Published
- 2021
40. Synthesis of phenanthridines via a novel photochemically-mediated cyclization and application to the synthesis of triphaeridine
- Author
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Songeziwe Ntsimango, Moira L. Bode, Kennedy J. Ngwira, and Charles B. de Koning
- Subjects
Biphenyl ,Trisphaeridine ,cyclization ,Scope (project management) ,synthesis ,radical cation ,aromatic compounds ,Science ,Organic chemistry ,Oxime ,Combinatorial chemistry ,Full Research Paper ,chemistry.chemical_compound ,Chemistry ,iminyl radical ,phenanthridines ,QD241-441 ,chemistry ,Radical ion ,Yield (chemistry) ,Product (mathematics) ,uv irradiation - Abstract
Readily synthesized biphenyl-2-carbaldehyde O-acetyl oximes were exposed to UV radiation affording phenanthridines. The scope and limitations of this novel reaction were explored. For example, exposure of 2',3'-dimethoxy-[1,1'-biphenyl]-2-carbaldehyde O-acetyl oxime to UV radiation afforded 4-methoxyphenanthridine in 54% yield. This methodology was applied to the synthesis of trisphaeridine to afford the product in four linear steps in an overall yield of 6.5% from 1-bromo-2,4,5-trimethoxybenzene.
- Published
- 2021
41. Could acetone O-(4-chlorophenylsulfonyl)oxime be a copper chelating and antioxidative molecule on maize seedlings?
- Author
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Fuat Yetişsin and İnci Kardeş
- Subjects
Antioxidant ,maize seedlings ,medicine.medical_treatment ,chemistry.chemical_element ,Plant Science ,Zea mays ,Antioxidants ,Acetone ,chemistry.chemical_compound ,Ascorbate Peroxidases ,Oximes ,medicine ,Environmental Chemistry ,Chelation ,Proline ,phenolic substances ,biology ,Superoxide Dismutase ,Hydrogen Peroxide ,Catalase ,Oxime ,Pollution ,Copper ,copper stress ,Oxidative Stress ,Biodegradation, Environmental ,antioxidant system ,Acetone O-(4-chlorophenylsulfonyl)oxime (AO) ,chemistry ,Distilled water ,Seedlings ,biology.protein ,Reactive Oxygen Species ,Nuclear chemistry - Abstract
The main purpose of study is to determine if Acetone O- (4-chlorophenylsulfonyl) oxime (AO) has a positive effect on maize seedlings under copper (Cu) stress or not. Seedlings were allocated to following experimental groups: 18-hour distilled water (DW) Control (C), ago 6-hour 0.66 mM AO + later 12-hour DW (AO), ago 6-hour DW + later 12-hour 1 mM Cu (Cu), ago 6-hour 0.66 mM AO + later 12-hour 1 mM Cu (AO + Cu). The results showed that AO + Cu caused approximately three times more copper accumulation compared to Cu treatment. AO and AO + Cu treatments significantly decreased membrane damage and H2O2 formation compared to its control. The proline content was significantly increased in AO and AO + Cu compared to its control. While the highest catalase, Guaiacol Peroxidase and superoxide dismutase activity was observed in Cu application, the highest ascorbate peroxidase activity was determined in AO application. It was observed that AO had a protective effect on chlorophyll content and RWC, but a positive effect on carotenoid content could not be determined. In addition, the effects of AO on the content of 17 phenolic substances in maize leaves were determined. In the light of the current findings, AO may prevent the formation of radical compounds. Novelty statement The fact that Acetone O-(4 chlorophenylsulfonyl) oxime (AO) caused approximately three times more copper accumulation indicates that it has a significant potential for phytoremediation studies. Despite the fact that AO resulted in approximately three times more copper accumulation, it is surprising that the Maize plant was able to continue its almost normal metabolic activities. AO alleviated the adverse effects of stress by affecting the hormones and antioxidant system of the plant. If AO is used with hyper accumulator plants, it may have the potential to obtain effective solutions in heavily copper-contaminated soils. © 2021 Taylor & Francis Group, LLC.
- Published
- 2021
42. Improved Synthesis of a Cyclic Glutamine Analogue Used in Antiviral Agents Targeting 3C and 3CL Proteases Including SARS-CoV-2 Mpro
- Author
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John C. Vederas and Wayne Vuong
- Subjects
Proteases ,Glutamine ,medicine.medical_treatment ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Antiviral Agents ,01 natural sciences ,03 medical and health sciences ,chemistry.chemical_compound ,Hydrogenolysis ,medicine ,Humans ,Protease Inhibitors ,Coronavirus 3C Proteases ,030304 developmental biology ,chemistry.chemical_classification ,0303 health sciences ,Protease ,SARS-CoV-2 ,010405 organic chemistry ,Organic Chemistry ,COVID-19 ,Note ,Oxime ,Combinatorial chemistry ,0104 chemical sciences ,Amino acid ,chemistry ,Pharmacophore - Abstract
An intermediate in the synthesis of numerous antiviral protease inhibitors is the glutamine analogue, (3S)-pyrrolid-2-one-3-yl-l-alanine. Preparations of compounds based on this pharmacophore are hindered by the lack of a reliably high yielding synthesis of protected forms of this amino acid. We describe an improved scalable route with readily available reagents and facile purification. This methodology employs γ-allylation of dimethyl N-BocGlu, further Boc N-protection, OsO4-periodate oxidation, O-Me oxime formation, and RaNi-catalyzed hydrogenolysis with concomitant cyclization under basic conditions.
- Published
- 2021
43. Visible-Light-Driven Photoredox-Catalyzed Three-Component Radical Cyanoalkylfluorination of Alkenes with Oxime Esters and a Fluoride Ion
- Author
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Jun Chen, Ying Cheng, Hao Qian, Bin Zhang, Wen-Jing Xiao, and Jia-Rong Chen
- Subjects
chemistry.chemical_classification ,Alkene ,Organic Chemistry ,Oxime ,Biochemistry ,Catalysis ,chemistry.chemical_compound ,chemistry ,Nucleophile ,Reagent ,Functional group ,Organic chemistry ,Physical and Theoretical Chemistry ,Fluoride ,Visible spectrum - Abstract
A metal-free, photoredox-catalyzed three-component cyanoalkylfluorination of alkenes under mild and redox-neutral conditions is reported. This protocol features use of readily available alkenes, oxime esters, and cost-effective nucleophilic fluoride reagents, giving diverse cyanoalkylfluorinated products with generally good yields. Excellent functional group tolerance and mild reaction conditions also render this protocol suitable for cyanoalkylfluorination of pharmaceutically relevant molecule-derived alkene.
- Published
- 2021
44. Selective C–C Bond Cleavage of Cycloalkanones by NaNO2/HCl
- Author
-
Tianyu He, Yu Zheng, Shenlin Huang, Dengfeng Chen, and Qian Shencheng
- Subjects
chemistry.chemical_compound ,chemistry ,Organic Chemistry ,Isocoumarins ,Physical and Theoretical Chemistry ,Fragmentation (cell biology) ,Oxime ,Biochemistry ,Medicinal chemistry ,Bond cleavage - Abstract
A novel selective fragmentation of cycloalkanones by NaNO2/HCl has been established. The C-C bond cleavage reaction proceeds smoothly under mild conditions, selectively affording versatile keto acids or oxime acids. The methodology can streamline the synthesis of valuable chiral molecules and isocoumarins from readily available feedstocks.
- Published
- 2021
45. Photoinduced Copper-Catalyzed Asymmetric C–O Cross-Coupling
- Author
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Xiao-Die Huan, Peng-Zi Wang, Jun Chen, Hao Qian, Yu-Jie Liang, Wen-Jing Xiao, Jia-Rong Chen, Bin Zhang, Wei Guan, and Guo-Qing Li
- Subjects
Allylic rearrangement ,Chemistry ,Heteroatom ,Photoredox catalysis ,General Chemistry ,Photochemistry ,Oxime ,Biochemistry ,Asymmetric induction ,Catalysis ,chemistry.chemical_compound ,Colloid and Surface Chemistry ,Density functional theory ,Bifunctional - Abstract
The construction of carbon-heteroatom bonds is one of the most active areas of research in organic chemistry because the function of organic molecules is often derived from the presence of heteroatoms. Although considerable advances have recently been achieved in radical-involved catalytic asymmetric C-N bond formation, there has been little progress in the corresponding C-O bond-forming processes. Here, we describe a photoinduced copper-catalyzed cross-coupling of readily available oxime esters and 1,3-dienes to generate diversely substituted allylic esters with high regio- and enantioselectivity (>75 examples; up to 95% ee). The reaction proceeds at room temperature under excitation by purple light-emitting diodes (LEDs) and features the use of a single, earth-abundant copper-based chiral catalyst as both the photoredox catalyst for radical generation and the source of asymmetric induction in C-O coupling. Combined experimental and density functional theory (DFT) computational studies suggest the formation of π-allylcopper complexes from redox-active oxime esters as bifunctional reagents and 1,3-dienes through a radical-polar crossover process.
- Published
- 2021
46. Transition‐Metal‐Free Visible Light‐Induced Imino‐trifluoromethylation of Unsaturated Oxime Esters: A Facile Access to CF 3 ‐Tethered Pyrrolines
- Author
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Ning Xu, Han He, Bin Chen, Kang Chen, Kang Guo, Jiawei Xu, and Yingguang Zhu
- Subjects
chemistry.chemical_compound ,Transition metal ,Chemistry ,Trifluoromethylation ,Organic Chemistry ,Photoredox catalysis ,Oxime ,Photochemistry ,Visible spectrum - Published
- 2021
47. Synthesis of BACE1 Inhibitors E2609/E2071 via Oxime–Olefin Cycloaddition Following a Process Risk Mitigation Strategy
- Author
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Farid Benayoud, Masayuki Omori, Yuichi Suzuki, Arani Chanda, Kazunori Wakasugi, Yuzo Watanabe, Akio Kayano, Paschalis Dimopoulos, Yoichi Kita, Kunitoshi Takeda, Toshihiko Kaneko, Mitsuo Nagai, Noboru Yamamoto, Takafumi Motoki, Kazuhiro Yoshizawa, Christopher Neil Farthing, Lily Lu, Matthew J. Schnaderbeck, Khan Afzal, Tasuku Ishida, Huiming Zhang, Mamoru Takaishi, Markus Bracke, Branko Mitasev, Dae-Shik Kim, Francis G. Fang, and Adrian Hall
- Subjects
Olefin fiber ,chemistry.chemical_compound ,business.industry ,Chemistry ,Scientific method ,Organic Chemistry ,Physical and Theoretical Chemistry ,business ,Oxime ,Combinatorial chemistry ,Risk management ,Cycloaddition - Published
- 2021
48. Synthesis and characterization of mononuclear oxime-based palladacycles incorporating phosphorus ylides: application as a catalyst in Suzuki cross coupling reactions and their biological activities
- Author
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Sepideh Samiee, Ahmadreza Shiralinia, and Elham Hoveizi
- Subjects
chemistry.chemical_compound ,Chemistry ,Phosphorus ,Materials Chemistry ,chemistry.chemical_element ,Organic chemistry ,Physical and Theoretical Chemistry ,Oxime ,Coupling reaction ,Catalysis ,Characterization (materials science) - Published
- 2021
49. Structural and optical properties of titania nanostructures obtained from oxime-modified titanium(IV) precursor
- Author
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Dalip Singh, Veena Dhayal, and Ajay Saini
- Subjects
Materials science ,Nanostructure ,Borosilicate glass ,Mechanical Engineering ,chemistry.chemical_element ,Condensed Matter Physics ,Oxime ,chemistry.chemical_compound ,chemistry ,Chemical engineering ,Mechanics of Materials ,Transmittance ,General Materials Science ,Pyrolytic carbon ,Deposition (chemistry) ,Titanium - Abstract
Spray pyrolytic deposition (SPD) of titania films on borosilicate glass substrates has been carried out using oxime-modified titanium(IV) isopropoxide, [Ti(OiPr)2{ONC(CH3)2}2]. Thermal study of the...
- Published
- 2021
50. Dihydrooxazine Byproduct of a McMurry–Melton Reaction en Route to a Synthetic Bacteriochlorin
- Author
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Vy-Phuong Tran, Nobuyuki Matsumoto, Phattananawee Nalaoh, Haoyu Jing, Chih-Yuan Chen, and Jonathan S. Lindsey
- Subjects
General Medicine ,bacteriochlorin ,dihydrodipyrrin ,dihydrooxazine ,McMurry ,Nef reaction ,nitronate ,oxime ,Paal–Knorr reaction - Abstract
A synthetic route to gem-dimethyl-substituted bacteriochlorins—models of native bacteriochlorophylls—relies on the formation of a dihydrodipyrrin precursor via a series of established reactions: van Leusen pyrrole formation, Vilsmeier formylation, Henry reaction, borohydride reduction, Michael addition, and McMurry–Melton pyrroline formation. The latter is the least known of the series. Here, the McMurry–Melton reaction of a 2-(6-oxo-2-nitrohexyl)pyrrole in the presence of TiCl3 and an ammonium acetate buffer formed the expected Δ1-pyrroline, as well as an unexpected polar, cyclic byproduct (a 5,6-dihydro-4H-1,2-oxazin-6-ol), each attached to the 2-methylpyrrole unit. Both species were characterized by single-crystal X-ray diffraction. The McMurry–Melton reaction is a type of intercepted Nef reaction (the transformation of a nitroalkyl motif into a carbonyl group), where both the Δ1-pyrroline and the dihydrooxazine derive from the reaction of the nitrogen derived from the nitro group upon complete or partial reductive deoxygenation, respectively, with the γ-keto group. The report also considers competing Nef and McMurry–Melton reactions, the nature of available TiCl3 reagents, and the use of ammonium acetate for buffering the TiCl3/HCl reagent.
- Published
- 2022
- Full Text
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