- PROTEIN-MACROMOLECULE CONJUGATES AND METHODS OF USE THEREOF
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The present disclosure provides protein-macromolecule conjugates, releasable linkers, and macromolecules, as defined herein. The disclosed conjugates provide unique properties that are based at least upon the properties of linker and number of linker-Macromolecule moieties. Also provided herein are a method of synthesis and use of conjugates in treating diseases and disorders.
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Paragraph 0390; 0391
(2021/04/10)
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- Nickel-Catalyzed Reversible Functional Group Metathesis between Aryl Nitriles and Aryl Thioethers
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We describe a new functional group metathesis between aryl nitriles and aryl thioethers. The catalytic system nickel/dcype is essential to achieve this fully reversible transformation in good to excellent yields. Furthermore, the cyanide- and thiol-free reaction shows high functional group tolerance and great efficiency for the late-stage derivatization of commercial molecules. Finally, synthetic applications demonstrate its versatility and utility in multistep synthesis.
- Delcaillau, Tristan,Boehm, Philip,Morandi, Bill
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supporting information
p. 3723 - 3728
(2021/04/07)
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- Iridium-Catalyzed ortho-C-H Borylation of Thioanisole Derivatives Using Bipyridine-Type Ligand
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A simple iridium catalytic system was developed that allows for a variety of 2-borylthioanisoles to be easily synthesized via ortho-selective C-H borylation of thioanisole derivatives. Once introduced, boryl and methylthio groups were converted by palladium-catalyzed transformations. Density functional theory calculations revealed that weak interactions, such as hydrogen bonding between the C-H bond of the SCH3 group and the oxygen atom of the boryl ligand, control the ortho-selectivity.
- Kuninobu, Yoichiro,Naito, Morio,Torigoe, Takeru,Yamanaka, Masahiro,Zeng, Jialin
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supporting information
(2020/05/08)
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- Copper-catalyzed and additive free decarboxylative trifluoromethylation of aromatic and heteroaromatic iodides
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A copper-catalyzed decarboxylative trifluoromethylation of (hetero)aromatic iodides has been developed. Importantly, this new copper-catalyzed reaction operates in the absence of any ligands and metal additives. The protocol shows good functional group tolerance and is compatible with heteroaromatic systems. The reaction proved scalable to a 15 mmol scale with increased yield. Finally, late-stage installation of the trifluoromethyl functionality afforded the N-trifluoroacetamide variant of the antidepressant agent, Prozac, demonstrating the applicability of the developed method.
- Johansen, Martin B.,Lindhardt, Anders T.
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p. 1417 - 1425
(2020/03/03)
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- Transition-Metal-Free Aryl-Heteroatom Bond Formation via C-S Bond Cleavage
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Aryl-heteroatom bonds (C-Het) are almost ubiquitously present in chemical molecules. However, methods for diverse C-Het bond formations from a simple substrate are limited. Herein, we report a convenient and efficient C-S bond transformation of aryl sulfoniums to various C-Het bonds (C-O, C-S, C-Sn, C-Si, C-Se) in the absence of any transition-metal catalyst. These reactions proceeded in mild conditions with a wide substrate scope.
- Zhao, Jian-Nan,Kayumov, Muzaffar,Wang, Dong-Yu,Zhang, Ao
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supporting information
p. 7303 - 7306
(2019/10/02)
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- Cathodic C-H Trifluoromethylation of Arenes and Heteroarenes Enabled by an in Situ-Generated Triflyltriethylammonium Complex
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While several trifluoromethylation reactions involving the electrochemical generation of CF3 radicals via anodic oxidation have been reported, the alternative cathodic, reductive radical generation has remained elusive. Herein, the first cathodic trifluoromethylation of arenes and heteroarenes is reported. The method is based on the electrochemical reduction of an unstable triflyltriethylammonium complex generated in situ from inexpensive triflyl chloride and triethylamine, which produces CF3 radicals that are trapped by the arenes on the cathode surface.
- Cantillo, David,Jud, Wolfgang,Kappe, C. Oliver,Maljuric, Snjezana
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supporting information
(2019/10/08)
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- Reduction of CO2 with NaBH4/I2 for the Conversion of Thiophenols to Aryl Methyl Sulfides
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We report a tandem reaction to realize reduction of carbon dioxide with thiophenols to generate aryl methyl sulfides under the NaBH4/I2 system with 18-crown-6 as the solvent. Thiophenols bearing electron-donating and electron-withdrawing groups are feasible in this reaction. Controlled experiment results indicate that 18-crown-6 plays a critical role in six-electron reduction of carbon dioxide.
- Zhang, Bo,Fan, Zhengning,Guo, Zhiqiang,Xi, Chanjuan
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p. 8661 - 8667
(2019/07/03)
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- Cesium carbonate-promoted synthesis of aryl methyl sulfides using: S -methylisothiourea sulfate under transition-metal-free conditions
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In the presence of cesium carbonate, an efficient synthesis of aryl methyl sulfides by the reactions of aryl halides with commercially available S-methylisothiourea sulfate is developed. This odourless and highly crystalline solid can be used as the subst
- Zhang, Caiyang,Zhou, You,Huang, Jintao,Tu, Canhui,Zhou, Xiaoai,Yin, Guodong
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p. 6316 - 6321
(2018/09/10)
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- Transalkylation of alkyl aryl sulfides with alkylating agents
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The reaction of methyl iodide with tert-butylphenylsulfide in DMF leads to a transalkylation that produces methylphenylsulfide. This transalkylation reaction was further studied by 1H NMR spectroscopy. The polarity of the solvent, the electron density on the sulfur atom, and the strength of the alkylating agent (MeI, EtI, BuI, dimethyl sulfate, or dimethyl carbonate) played important roles in the reaction. The suggested mechanism of the reaction involves the formation of a dialkyl aryl sulfonium salt that subsequently eliminates the radical. This mechanism was supported by the observation of higher conversion rates for compounds with more branched alkyl groups on the sulfur atom, which may lead to the formation of more stable radicals.
- Nawrot, Daria,Koleni?, Marek,Kune?, Ji?í,Kostelansky, Filip,Miletin, Miroslav,Novakova, Veronika,Zimcik, Petr
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p. 594 - 599
(2018/01/01)
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- Palladium-Catalyzed Thiomethylation via a Three-Component Cross-Coupling Strategy
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In this report, the combination of masked inorganic sulfur and dimethyl carbonate was designed to achieve thiomethylated cross coupling of aryl chlorides. Remarkably, this powerful strategy realized thiomethylation of nucleosides bearing unprotected ribose, chloride-containing pharmaceuticals with late-stage coupling, and herbicides possessing multiple heteroatoms and steric hindrance. Moreover, this protocol is practically amenable to multigram-scale synthesis with a lower catalysis loading and a higher yield.
- Wang, Ming,Qiao, Zongjun,Zhao, Jiaoyan,Jiang, Xuefeng
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supporting information
p. 6193 - 6197
(2018/09/25)
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- Methyl aryl thioether compound, and synthetic method and applications thereof
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The invention discloses a methyl aryl thioether compound represented by formula 2, and a synthetic method and applications thereof. According to the synthetic method, in a reaction solvent, an aryl halide or an aromatic halide, dimethyl carbonate, and potassium thioacetate are taken as reaction raw materials, reaction is carried out in the presence of metal palladium catalyst under the action of a ligand and an alkali so as to obtain the methyl aryl thioether compound. The reaction conditions of the synthetic method are mild; the raw materials are cheap and easily available; reaction operation is simple; yield is relatively high. The methyl aryl thioether compound can be used for providing skeleton structures for the synthesis of a plurality of natural products and medicines, and can be widely applied in industrialized large-scale production.
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Paragraph 0086; 0087; 0088
(2017/07/21)
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- Palladium-Catalyzed ipso-Borylation of Aryl Sulfides with Diborons
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A catalytic Miyaura-type ipso-borylation of aryl sulfides with diboron reagents has been achieved, providing arylboronate esters of synthetic use. The key conditions to transform inherently reluctant C-S bonds into C-B bonds include a palladium-NHC (N-heterocyclic carbene) precatalyst, bis(pinacolato)diboron, and lithium hexamethyldisilazide. This protocol is applicable to a reasonable range of aryl alkyl sulfides. Twofold borylation was observed in the reaction of diphenyl sulfide.
- Bhanuchandra,Baralle, Alexandre,Otsuka, Shinya,Nogi, Keisuke,Yorimitsu, Hideki,Osuka, Atsuhiro
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supporting information
p. 2966 - 2969
(2016/07/06)
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- Studies on the synthesis, stability and conformation of 2-sulfonyl-oxetane fragments
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2-(Arylsulfonyl)oxetanes have been prepared as new structural motifs of interest for medicinal chemistry. These are designed to fit within fragment space and be suitable for screening in fragment based drug discovery, as well as being suitable for further elaboration or incorporation into drug-like compounds. The oxetane ring is constructed through an efficient C-C bond forming cyclisation which allows the incorporation of a wide range of aryl-sulfonyl groups. Furthermore, biaryl-containing compounds can be accessed through Suzuki-Miyaura coupling from halogenated derivatives. With a number of oxetane containing fragment compounds available, their pH stability was assessed, indicating good half-life values for mono-substituted aryl sulfonyl oxetanes across the pH range (1 to 10). Solubility and metabolic stability data is also reported. Finally, the conformation of the fragments is assessed computationally, providing an indication of possible binding orientations.
- Morgan,Hollingsworth,Bull
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supporting information
p. 5265 - 5272
(2015/05/13)
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- N-Imidazolylation of Sulfoximines from N-Cyano Sulfoximines, 1-Alkynes, and N-Sulfonyl Azides
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The rhodium-catalyzed N-imidazolylation of N-sulfonyl-1,2,3-triazoles with a variety of N-cyano sulfoximines has been developed for the synthesis of N-imidazolyl sulfoximines via elimination of molecular nitrogen. Copper-catalyzed [3+2] cycloaddition followed by rhodium-catalyzed N-imidazolylation from 1-alkynes, N-sulfonyl azides, and N-cyano sulfoximines is also demonstrated for the synthesis of N-imidazolyl sulfoximines in a one-pot procedure.
- Kim, Sanghyuck,Kim, Ji Eun,Lee, Jinsub,Lee, Phil Ho
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supporting information
p. 3707 - 3717
(2016/01/25)
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- Investigation of the scope and mechanism of copper catalyzed regioselective methylthiolation of aryl halides Dedicated to Professor Dr. Irina Beletskaya
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Methylthiolation of structurally diverse aryl halides was accomplished under fluoride free conditions using catalytic amounts of CuI, and DMSO as the methylthiolation source. Optimization studies unveiled several varieties of promoters among which Zn(OAc)2 was found ideal. The analogous reaction with DMSO-d6 afforded corresponding deuterated aryl methyl thioether with 99% purity. Mechanistic studies revealed CuSMe as the active methylthiolation agent.
- Joseph, P.J. Amal,Priyadarshini,Kantam, M. Lakshmi,Sreedhar
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supporting information
p. 8276 - 8283
(2013/09/02)
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- Organocatalytic visible light mediated synthesis of aryl sulfides
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Photo-sensitized synthesis of arylsulfides from arenediazonium salts in the presence of eosin Y has been developed. This protocol exhibits high functional group tolerance and a wide substrate scope and is an attractive alternative to the thermal reaction that involves explosive intermediates.
- Majek, Michal,Von Wangelin, Axel Jacobi
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supporting information
p. 5507 - 5509
(2013/06/27)
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- Copper-catalyzed trifluoromethylation of aryl- and vinylboronic acids with generation of CF3-radicals
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The selective trifluoromethylation of aryl- and vinylboronic acids proceeds smoothly with CF3SO2Na (Langlois reagent) in the presence of copper catalysts and t-BuOOH. Therefore, the method relies both on transition metal catalysis an
- Li, Yang,Wu, Lipeng,Neumann, Helfried,Beller, Matthias
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supporting information
p. 2628 - 2630
(2013/04/23)
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- Efficient synthesis of aryl methyl sulfide derivatives using (methylthio)trimethylsilane as methylthiolation reagent
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The synthesis of various aryl methyl sulfides has been achieved by treatment of nitroarenes with a combination of (methylthio)trimethylsilane and cesium carbonate in dimethylsulfoxide. This reaction gives access to aryl methyl sulfide derivatives in high yields. Copyright
- Qiao, Qi,Dominique, Romyr,Sidduri, Achyutharao,Lou, Jianping,Goodnow, Robert A.
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scheme or table
p. 3691 - 3698
(2010/12/25)
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- New Synthetic Routes to Unsymmetrical Diorganyl Sulfides
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A number of new methods for preparing unsymmetrical diorganyl sulfides was proposed. The methods rely on generation of thiolate anions from thiols, isothiuronium salts, and disulfides in the system hydrazine hydrate-KOH, followed by alkylation of the anions with alkyl halides. The hydrazine hydrate plays the role of medium and reducing agent, which prevents side thiol oxidation. The yield of sulfides reaches 98%. The reaction products are readily separated from the aqueous-hydrazine layer and purified by distillation. The yield of sulfides is reduced by a deficit of alkali and by increasing chain length and functionalization of alkyl groups in the alkyl halide. The reactivity of alkyl halides is independent of the nature of the halogen. From isothiuronium salts, 2-pyridyl sulfides were obtained in the highest yields.
- Deryagina,Korchevin,Papernaya
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p. 812 - 815
(2007/10/03)
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- Destabilizing dπ-pπ orbital interactions and the alkylation reactions of iron(II)-thiolate complexes
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For CpFe(CO)2SR (1) (R = C6H4-p-Z; Z = OMe, H, Cl, CF3, NO2) the π-type interaction between formally occupied metal d orbitals and the sulfur lone pair that is principally 3p in character has been modeled with Fenske-Hall molecular orbital calculations and experimentally investigated by gas-phase photoelectron spectroscopy. A calculation for 1 (R = H) predicts that the highest occupied molecular orbital (HOMO) is metal-sulfur antibonding and largely sulfur in character. The observed HOMO ionization energies of 1 correlate with several chemical properties, including the rate of reaction of the thiolate ligand with alkyl halides. Solvent and substituent effects on the reaction rate favor a mechanism involving nucleophilic displacement of the halide by the coordinated thiolate ligand. The nucleophilicity of the coordinated thiolate ligand of 1 is related to the metal-sulfur dπ-pπ antibonding interactions.
- Ashby, Michael T.,Enemark, John H.,Lichtenberger, Dennis L.
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p. 191 - 197
(2008/10/08)
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