- Influence of Solvent Polarity on the Radiationless Decay of the Intramolecular Exciplexes of ω-Phenyl-α-N,N-dimethylaminoalkanes
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Using optoacoustic spectroscopy, the radiationless decay processes of intramolecular exciplexes of ω-phenyl-α-N,N-dimethylaminoalkanes are investigated.Upon increase of the solvent polarity, the relative efficiency of the intersystem crossing process from the singlet exciplex to the locally excited triplet decreases compared to the efficiency of the internal conversion process.These results can be rationalized in the framework of the current electron-transfer theory and compared to the results obtained for other ω-aryl-α-N,N-dimethylaminoalkanes.
- Auweraer, M. Van der,Viaene, L.,Haver, Ph. Van,Schryver, F. C. De
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Read Online
- Synthesis of derivatives of [I-131] phenylalkylamines for brain mapping
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The synthesis and spectral properties of new radioiodinated phenylalkylamines like 2-[131I]-iodo-4,5-dimethoxyphenethylamine, 2- [131I]-iodo-4,5-dimethoxy-N,N-dimethylphenethylamine 2-[131I]- iodophenethylamine, 2-[131I]-iodo-N,N-dimethylphenethylamine, 2-[131I]- iodo-3,4,5-trimethoxy-phenethylamine (mescaline) are described for the first time. These compounds are of biological importance and can be used for brain mapping with SPECT technology.
- Sintas, Jose A.,Vitale, Arturo A.
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Read Online
- Remarkably Efficient Iridium Catalysts for Directed C(sp2)-H and C(sp3)-H Borylation of Diverse Classes of Substrates
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Here we describe the discovery of a new class of C-H borylation catalysts and their use for regioselective C-H borylation of aromatic, heteroaromatic, and aliphatic systems. The new catalysts have Ir-C(thienyl) or Ir-C(furyl) anionic ligands instead of the diamine-type neutral chelating ligands used in the standard C-H borylation conditions. It is reported that the employment of these newly discovered catalysts show excellent reactivity and ortho-selectivity for diverse classes of aromatic substrates with high isolated yields. Moreover, the catalysts proved to be efficient for a wide number of aliphatic substrates for selective C(sp3)-H bond borylations. Heterocyclic molecules are selectively borylated using the inherently elevated reactivity of the C-H bonds. A number of late-stage C-H functionalization have been described using the same catalysts. Furthermore, we show that one of the catalysts could be used even in open air for the C(sp2)-H and C(sp3)-H borylations enabling the method more general. Preliminary mechanistic studies suggest that the active catalytic intermediate is the Ir(bis)boryl complex, and the attached ligand acts as bidentate ligand. Collectively, this study underlines the discovery of new class of C-H borylation catalysts that should find wide application in the context of C-H functionalization chemistry.
- Chattopadhyay, Buddhadeb,Hassan, Mirja Md Mahamudul,Hoque, Md Emdadul
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supporting information
p. 5022 - 5037
(2021/05/04)
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- Simplified preparation of a graphene-co-shelled Ni/NiO@C nano-catalyst and its application in theN-dimethylation synthesis of amines under mild conditions
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The development of Earth-abundant, reusable and non-toxic heterogeneous catalysts to be applied in the pharmaceutical industry for bio-active relevant compound synthesis remains an important goal of general chemical research.N-methylated compounds, as one of the most essential bioactive compounds, have been widely used in the fine and bulk chemical industries for the production of high-value chemicals. Herein, an environmentally friendly and simplified method for the preparation of graphene encapsulated Ni/NiO nanoalloy catalysts (Ni/NiO@C) was developed for the first time, for the highly selective synthesis ofN-methylated compounds using various functional amines and aldehydes under easy to handle, and industrially applicable conditions. A large number of primary and secondary amines (more than 70 examples) could be converted to the correspondingN,N-dimethylamines with the participation of different functional aldehydes, with an average yield of over 95%. A gram-scale synthesis also demonstrated a similar yield when compared with the benchmark test. In addition, it was further proved that the catalyst could easily be recycled because of its intrinsic magnetism and reused up to 10 times without losing its activity and selectivity. Also, for the first time, the tandem synthesis ofN,N-dimethylamine products in a one-pot process, using only a single earth-abundant metal catalyst, whose activity and selectivity were more than 99% and 94%, respectively, for all tested substrates, was developed. Overall, the advantages of this newly developed method include operational simplicity, high stability, easy recyclability, cost-effectiveness of the catalyst, and good functional group compatibility for the synthesis ofN-methylation products as well as the industrially applicable tandem synthesis process.
- Liu, Jianguo,Ma, Longlong,Song, Yanpei,Zhang, Mingyue,Zhuang, Xiuzheng
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supporting information
p. 4604 - 4617
(2021/06/30)
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- Dimethylamination of Primary Alcohols Using a Homogeneous Iridium Catalyst: A Synthetic Method for N, N-Dimethylamine Derivatives
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A new catalytic system for N,N-dimethylamination of primary alcohols using aqueous dimethylamine in the absence of additional organic solvents has been developed. The reaction proceeds via borrowing hydrogen processes, which are atom-efficient and environmentally benign. An iridium catalyst bearing an N-heterocyclic carbene (NHC) ligand exhibited high performance, without showing any deactivation under aqueous conditions. In addition, valuable N,N-dimethylamine derivatives, including biologically active and pharmaceutical molecules, were synthesized. The practical application of this methodology was demonstrated by a gram-scale reaction.
- Jeong, Jaeyoung,Fujita, Ken-Ichi
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p. 4053 - 4060
(2021/03/09)
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- Additive-freeN-methylation of amines with methanol over supported iridium catalyst
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An efficient and versatile zinc oxide-supported iridium (Ir/ZnO) catalyst was developed to catalyze the additive-freeN-methylation of amines with methanol. Mechanistic studies suggested that the high catalytic reactivity is rooted in the small sizes (1.4 nm) of Ir nanoparticles and the high ratio (93%) of oxidized iridium species (IrOx, Ir3+and Ir4+) on the catalyst. Moreover, the delicate cooperation between the IrOxand ZnO support also promoted its high reactivity. The selectivity of this catalyticN-methylation was controllable between dimethylation and monomethylation by carefully tuning the catalyst loading and reaction solvent. Specifically, neat methanol with high catalyst loading (2 mol% Ir) favored the formation ofN,N-dimethylated amine, while the mesitylene/methanol mixture with low catalyst loading (0.5 mol% Ir) was prone to producing mono-N-methylated amines. An environmentally benign continuous flow system with a recycled mode was also developed for the efficient production ofN-methylated amines. With optimal flow rates and amine concentrations, a variety ofN-methylamines were produced with good to excellent yields in this Ir/ZnO-based flow system, providing a starting point for the clean and efficient production ofN-methylamines with this cost-effective chemical process.
- Liu, Xiang,Loh, Teck-Peng,Qiang, Wenwen,Wang, Jing,Ye, Sen,Zhu, Longfei
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p. 3364 - 3375
(2021/06/06)
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- Method for realizing N-alkylation by using alcohols as carbon source under photocatalysis
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The invention discloses a method for realizing N-alkylation by using alcohols as a carbon source under photocatalysis, and belongs to the technical field of catalytic synthesis. Alcohol, a substrate raw material and a catalyst are placed in a reaction device, ultraviolet and/or visible light irradiation is carried out in an inert atmosphere, after the irradiation is finished, solid-liquid separation is carried out to remove the catalyst, and an N-alkylation product can be obtained through extraction, distillation and purification, wherein the substrate raw material comprises any one of an amine compound, an aromatic nitro compound or an aromatic nitrile compound, the alcohol comprises any one or more of soluble primary alcohols, and the catalyst is metal oxide/titanium dioxide or metal sulfide/titanium dioxide. The method is simple and easy to operate, can be used for efficient photocatalysis one-pot multi-step hydrogenation N-alkylation reaction, and is mild in reaction condition, high in chemical selectivity of N-alkylamine, good in catalyst stability and easy to recycle.
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Paragraph 0048-0056; 0058
(2021/03/13)
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- CONJUGATES OF AN ELECTRON-DONATING NITROGEN OR TERTIARY AMINE COMPRISING COMPOUNDS
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The present invention relates to conjugates of an electron-donating heteroaromatic nitrogen or tertiary amine comprising drugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions comprising said conjugates and the use of said conjugates as medicaments.
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Page/Page column 79
(2021/01/22)
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- B(C6F5)3-Catalyzed Deoxygenative Reduction of Amides to Amines with Ammonia Borane
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The first B(C6F5)3-catalyzed deoxygenative reduction of amides into the corresponding amines with readily accessible and stable ammonia borane (AB) as a reducing agent under mild reaction conditions is reported. This metal-free protocol provides facile access to a wide range of structurally diverse amine products in good to excellent yields, and various functional groups including those that are reduction-sensitive were well tolerated. This new method is also applicable to chiral amide substrates without erosion of the enantiomeric purity. The role of BF3 ? OEt2 co-catalyst in this reaction is to activate the amide carbonyl group via the in situ formation of an amide-boron adduct. (Figure presented.).
- Pan, Yixiao,Luo, Zhenli,Han, Jiahong,Xu, Xin,Chen, Changjun,Zhao, Haoqiang,Xu, Lijin,Fan, Qinghua,Xiao, Jianliang
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supporting information
p. 2301 - 2308
(2019/01/30)
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- Mechanistic study of the selective hydrogenation of carboxylic acid derivatives over supported rhenium catalysts
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The structure and performance of TiO2-supported Re (Re/TiO2) catalysts for selective hydrogenation of carboxylic acid derivatives have been investigated. Re/TiO2 promotes selective hydrogenation reactions of carboxylic acids and esters that form the corresponding alcohols, and of amides that generate the corresponding amines. These processes are not accompanied by reduction of aromatic moieties. A Re loading amount of 5 wt% and a catalyst pretreatment with H2 at 500 °C were identified as being optimal to obtain the highest catalytic activity for the hydrogenation processes. The results of studies using various characterization methods, including X-ray diffraction (XRD), X-ray absorption fine structure (XAFS), X-ray photoelectron spectroscopy (XPS), and scanning transmission electron microscopy (STEM), indicate that the Re species responsible for the catalytic hydrogenation processes have sub-nanometer to a few nanometer sizes and average oxidation states higher than 0 and below +4. The presence of either a carboxylic acid and/or its corresponding alcohol is critical for preventing the Re/TiO2 catalyst from promoting production of dearomatized byproducts. Although Re/TiO2 is intrinsically capable of hydrogenating aromatic rings, carboxylic acids, alcohols, amides, and amines strongly adsorb on the Re species, which leads to suppression of this process. Moreover, the developed catalytic system was applied to selective hydrogenation of triglycerides that form the corresponding alcohols.
- Toyao, Takashi,Ting, Kah Wei,Siddiki, S. M. A. Hakim,Touchy, Abeda S.,Onodera, Wataru,Maeno, Zen,Ariga-Miwa, Hiroko,Kanda, Yasuharu,Asakura, Kiyotaka,Shimizu, Ken-ichi
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p. 5413 - 5424
(2019/10/29)
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- N-Methylation of amines and nitroarenes with methanol using heterogeneous platinum catalysts
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We report herein the selective N-methylation of amines and nitroarenes with methanol under basic conditions using carbon-supported Pt nanoparticles (Pt/C) as a heterogeneous catalyst. This method is widely applicable to four types of N-methylation reactions: (1) N,N-dimethylation of aliphatic amines under N2, (2) N-monomethylation of aliphatic amines under 40 bar H2, (3) N-monomethylation of aromatic amines under N2, and (4) tandem synthesis of N-methyl anilines from nitroarenes and methanol under 2 bar H2. All these reactions under the same catalytic system showed high yields of the corresponding methylamines for a wide range of substrates, high turnover number (TON), and good catalyst reusability. Mechanistic studies suggested that the reaction proceeded via a borrowing hydrogen methodology. Kinetic results combined with density functional theory (DFT) calculations revealed that the high performance of Pt/C was ascribed to the moderate metal–hydrogen bond strength of Pt.
- Jamil, Md.A.R.,Touchy, Abeda S.,Rashed, Md. Nurnobi,Ting, Kah Wei,Siddiki, S.M.A. Hakim,Toyao, Takashi,Maeno, Zen,Shimizu, Ken-ichi
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- Selective synthesis of mono- and di-methylated amines using methanol and sodium azide as C1 and N1 sources
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A Ru(ii) complex mediated synthesis of various N,N-dimethyl and N-monomethyl amines from organic azides using methanol as a methylating agent is reported. This methodology was successfully applied for a one-pot reaction of bromide derivatives and sodium azide in methanol. Notably, by controlling the reaction time several N-monomethylated and N,N-dimethylated amines were synthesized selectively. The practical applicability of this tandem process was revealed by preparative scale reactions with different organic azides and synthesis of an anti-vertigo drug betahistine. Several kinetic experiments and DFT studies were carried out to understand the mechanism of this transformation.
- Chakrabarti, Kaushik,Mishra, Anju,Panja, Dibyajyoti,Paul, Bhaskar,Kundu, Sabuj
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supporting information
p. 3339 - 3345
(2018/07/29)
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- Selective Monomethylation of Amines with Methanol as the C1 Source
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The N-monomethyl functionality is a common motif in a variety of synthetic and natural compounds. However, facile access to such compounds remains a fundamental challenge in organic synthesis owing to selectivity issues caused by overmethylation. To address this issue, we have developed a method for the selective, catalytic monomethylation of various structurally and functionally diverse amines, including typically problematic primary aliphatic amines, using methanol as the methylating agent, which is a sustainable chemical feedstock. Kinetic control of the aliphatic amine monomethylation was achieved by using a readily available ruthenium catalyst at an adequate temperature under hydrogen pressure. Various substrates including bio-related molecules and pharmaceuticals were selectively monomethylated, demonstrating the general utility of the developed method.
- Choi, Geunho,Hong, Soon Hyeok
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supporting information
p. 6166 - 6170
(2018/04/30)
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- Methylation of Amines and Ketones with Methanol Catalyzed by an Iridium Complex Bearing a 2-Hydroxypyridylmethylene Fragment
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Reaction of complex [Cp?Ir(HOC5H3CH2C5H3OH)Cl][Cl] (1) with AgOTf generated the product [Cp?Ir(HOC5H3CH2C5H3OH)(H2O)][OTf]2 (2), which was further transformed to the complex [Cp?Ir(OC5H3CH2C5H3O)(H2O)] (3) in the presence of t-BuONa via -OH deprotonation. Complexes 1-3 exhibited high activity for the methylation of amines and ketones. These C-C and C-N coupling reactions proceeded in air with 1 mol % catalyst loading in the presence of K2CO3.
- Deng, Danfeng,Hu, Bowen,Yang, Min,Chen, Dafa
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p. 3353 - 3359
(2018/09/25)
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- Graphene-enhanced platinum-catalysed hydrosilylation of amides and chalcones: A sustainable strategy allocated with in situ heterogenization and multitask application of H2PtCl6
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We describe a new sustainable strategy for the comprehensive utilization of a platinum catalyst in different organic transformations, in which an organosilicon/graphene-supported platinum catalyst prepared from a simple hydrosilylation-type reduction could be further used in the 1,4-hydrosilylation of chalcones. The rationally designed and in situ formed Pt@G@Si nanocatalyst is demonstrated to be highly effective in the 1,4-hydrosilylation of α,β-unsaturated enones, allowing for the facile synthesis of a variety of otherwise inaccessible substituted silyl enolates. In addition, with the aid of platinum catalyst residue and TBAF, the one-pot downstream Michael addition of substituted silyl enolates to alkyl acrylates is also reported in this work.
- Li, Ning,Dong, Xiao-Yun,Zhang, Jing-Lei,Yang, Ke-Fang,Zheng, Zhan-Jiang,Zhang, Wei-Qiang,Gao, Zi-Wei,Xu, Li-Wen
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p. 50729 - 50738
(2017/11/10)
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- Mild Hydrogenation of Amides to Amines over a Platinum-Vanadium Bimetallic Catalyst
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Hydrogenation of amides to amines is an important reaction, but the need for high temperatures and H2 pressures is a problem. Catalysts that are effective under mild reaction conditions, that is, lower than 30 bar H2 and 70 °C, have not yet been reported. Here, the mild hydrogenation of amides was achieved for the first time by using a Pt-V bimetallic catalyst. Amide hydrogenation, at either 1 bar H2 at 70 °C or 5 bar H2 at room temperature was achieved using the bimetallic catalyst. The mild reaction conditions enable highly selective hydrogenation of various amides to the corresponding amines, while inhibiting arene hydrogenation. Catalyst characterization showed that the origin of the catalytic activity for the bimetallic catalyst is the oxophilic V-decorated Pt nanoparticles, which are 2 nm in diameter.
- Mitsudome, Takato,Miyagawa, Kazuya,Maeno, Zen,Mizugaki, Tomoo,Jitsukawa, Koichiro,Yamasaki, Jun,Kitagawa, Yasutaka,Kaneda, Kiyotomi
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supporting information
p. 9381 - 9385
(2017/08/01)
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- Rhenium-Loaded TiO2: A Highly Versatile and Chemoselective Catalyst for the Hydrogenation of Carboxylic Acid Derivatives and the N-Methylation of Amines Using H2 and CO2
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Herein, we report a heterogeneous TiO2-supported Re catalyst (Re/TiO2) that promotes various selective hydrogenation reactions, which includes the hydrogenation of esters to alcohols, the hydrogenation of amides to amines, and the N-methylation of amines, by using H2 and CO2. Initially, Re/TiO2 was evaluated in the context of the selective hydrogenation of 3-phenylpropionic acid methyl ester to afford 3-phenylpropanol (pH2 =5 MPa, =5 MPa, T=180 °C), which revealed a superior performance over other catalysts that we tested in this study. In contrast to other typical heterogeneous catalysts, hydrogenation reactions with Re/TiO2 did not produce dearomatized byproducts. DFT studies suggested that the high selectivity for the formation of alcohols in favor of the hydrogenation of aromatic rings is ascribed to the higher affinity of Re towards the COOCH3 group than to the benzene ring. Moreover, Re/TiO2 showed a wide substrate scope for the hydrogenation reaction (19 examples). Subsequently, this Re/TiO2 catalyst was applied to the hydrogenation of amides, the N-methylation of amines, and the N-alkylation of amines with carboxylic acids or esters.
- Toyao, Takashi,Siddiki,Morita, Yoshitsugu,Kamachi, Takashi,Touchy, Abeda S.,Onodera, Wataru,Kon, Kenichi,Furukawa, Shinya,Ariga, Hiroko,Asakura, Kiyotaka,Yoshizawa, Kazunari,Shimizu, Ken-Ichi
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supporting information
p. 14848 - 14859
(2017/10/27)
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- Method for implementing amine compound N-methylation by photocatalysis
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The invention belongs to the technical field of photocatalysis synthesis, and particularly relates to a method for implementing amine compound N-methylation by photocatalysis. The method includes the steps: 1) adding photocatalyst TiO2 and N-methylation carbon sources into a photocatalysis reactor to form a reaction system, and stirring the reaction system under ultraviolet irradiation; 2) adding reducing agents and amine compounds into the reaction system obtained in the step 1), and continually stirring mixture under ultraviolet irradiation to obtain N-methylation products. Compared with the prior art, the preparation method has the main advantages that selected raw materials are low in cost and toxicity, reaction conditions are mild, energy consumption is less, used catalysts are low in cost and easy to obtain, reaction operations are simple, and products are high in yield and good in selectivity.
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Paragraph 0032; 0033
(2017/09/01)
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- Photochemical Activation of Tertiary Amines for Applications in Studying Cell Physiology
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Representative tertiary amines were linked to the 8-cyano-7-hydroxyquinolinyl (CyHQ) photoremovable protecting group (PPG) to create photoactivatable forms suitable for use in studying cell physiology. The photoactivation of tamoxifen and 4-hydroxytamoxifen, which can be used to activate Cre recombinase and CRISPR-Cas9 gene editing, demonstrated that highly efficient release of bioactive molecules could be achieved through one- and two-photon excitation (1PE and 2PE). CyHQ-protected anilines underwent a photoaza-Claisen rearrangement instead of releasing amines. Time-resolved spectroscopic studies revealed that photorelease of the tertiary amines was extremely fast, occurring from a singlet excited state of CyHQ on the 70 ps time scale.
- Asad, Naeem,Deodato, Davide,Lan, Xin,Widegren, Magnus B.,Phillips, David Lee,Du, Lili,Dore, Timothy M.
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supporting information
p. 12591 - 12600
(2017/09/23)
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- Ruthenium-Catalyzed Methylation of Amines with Paraformaldehyde in Water under Mild Conditions
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Methylated amines are highly important for a variety of pharmaceutical and agrochemical applications. Existing routes for their formation result in the production of large amounts of waste or require high reaction temperatures, both of which impact the ecological and economical footprint of the methodologies. Herein, we report the ruthenium-catalyzed reductive methylation of a range of aliphatic amines, using paraformaldehyde as both substrate and hydrogen source, in combination with water. This reaction proceeds under mild aqueous reaction conditions. Additionally the use of a secondary phase for catalyst retention and recycling has been investigated with promising results.
- van der Waals, Dominic,Heim, Leo. E.,Gedig, Christian,Herbrik, Fabian,Vallazza, Simona,Prechtl, Martin H. G.
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p. 2343 - 2347
(2016/10/24)
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- Synthetic analogs of stryphnusin isolated from the marine sponge: Stryphnus fortis inhibit acetylcholinesterase with no effect on muscle function or neuromuscular transmission
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The marine secondary metabolite stryphnusin (1) was isolated from the boreal sponge Stryphnus fortis, collected off the Norwegian coast. Given its resemblance to other natural acetylcholinesterase antagonists, it was evaluated against electric eel acetylcholinesterase and displayed inhibitory activity. A library of twelve synthetic phenethylamine analogs, 2a-7a and 2b-7b, containing tertiary and quaternary amines respectively were synthesized to investigate the individual structural contributions to the activity. Compound 7b was the strongest competitive inhibitor of both acetylcholinesterase and butyrylcholinesterase with IC50 values of 57 and 20 μM, respectively. This inhibitory activity is one order of magnitude higher than the positive control physostigmine, and is comparable with several other marine acetylcholinesterase inhibitors. The physiological effect of compound 7b on muscle function and neuromuscular transmission was studied and revealed a selective mode of action at the investigated concentration. This data is of importance as the interference of therapeutic acetylcholinesterase inhibitors with neuromuscular transmission can be problematic and lead to unwanted side effects. The current findings also provide additional insights into the structure-activity relationship of both natural and synthetic acetylcholinesterase inhibitors.
- Moodie, Lindon W. K.,?u?ek, Monika C.,Frange?, Robert,Andersen, Jeanette H.,Hansen, Espen,Olsen, Elisabeth K.,Cergolj, Marija,Sep?i?, Kristina,Hansen, Kine ?.,Svenson, Johan
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p. 11220 - 11229
(2016/12/07)
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- Preparation method for alpha-cyanoamine
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The invention discloses a preparation method for alpha-cyanoamine. According to the method, the product alpha-cyanoamine is prepared through nucleophilic substitution in a mixed solvent in the presence of an oxidizing agent with an amine compound and cyanoacetic acid as reactants, iodide as a catalyst and sodium acetate as alkali. The catalyst used in the method has high reactivity; reaction conditions are mild; the application scope of a substrate is wide; post-treatment is convenient; the yield of the target product is high; preparation process is simple, green and environment-friendly; and used raw materials are widely available.
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Paragraph 0082; 0083
(2016/10/07)
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- Transition metal-free methylation of amines with formaldehyde as the reductant and methyl source
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A simple transition metal-free procedure using formaldehyde for the N,N-dimethylation and N-methylation of primary and secondary anilines is reported. The reaction showed limitations on sterically hindered and electron-withdrawing anilines, but is successful on amines with electron-donating substituents. Formaldehyde acts as both the reducing agent and the carbon source in the reaction.
- Man, Nikki Y.T.,Li, Wanfang,Stewart, Scott G.,Wu, Xiao-Feng
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p. 345 - 347
(2015/11/25)
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- Convenient Reductive Methylation of Amines with Carbonates at Room Temperature
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Methylation of amines is a fundamental and commonly used reaction in organic synthesis. Many methods are known including various reductive methylations using formaldehyde, formic acid, or carbon dioxide in the presence of reductants. However, several of these methods suffer from limited substrate scope and chemoselectivity because of the different nucleophilicities of substrates. In this respect, the combination of carbonates and hydrosilanes is a valuable methylation source in the presence of Pt-based catalysts. This highly tunable method allows for methylation of both aromatic and aliphatic amines, and chemoselective methylation of aminoalcohols and diamines. Notably, the in situ-formed catalyst can also be used for the reduction of carbonates to methanol at room temperature. Mechanistic insights on intermediates formed during the reaction pathway were obtained by using ESI mass spectrometry.
- Li, Yuehui,Sorribes, Iván,Vicent, Cristian,Junge, Kathrin,Beller, Matthias
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p. 16759 - 16763
(2015/11/16)
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- METHOD FOR PRODUCING N-SUBSTITUTED AMINE COMPOUNDS THROUGH CATALYZED ALKYLATION
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The invention relates to a method for producing a N-substituted amine compound by catalyzed alkylation. The method uses amine and alcohol or two kinds of amines as the reaction materials, employs composite metal oxides catalyst at a reaction temperature of 80-180° C. to catalyze the reaction for 6-36 hours, so as to produce the N-substituted amine compound. The reaction condition of the method of the invention is relatively moderate, using a catalyst made of cheap non-noble metals, which is non-caustic and easy to be separated and reused. The reaction does not need any medium and has relatively high conversion rate and selectivity.
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Paragraph 0044
(2014/02/16)
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- Metal-free catalyst for the chemoselective methylation of amines using carbon dioxide as a carbon source
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N-methylation of amines is an important step in the synthesis of many pharmaceuticals and has been widely applied in the preparation of other key intermediates and chemicals. Therefore, the development of efficient methylation methods has attracted considerable attention. In this respect, carbon dioxide is an attractive C1 building block because it is an abundant, renewable, and nontoxic carbon source. Consequently, we developed a highly chemoselective, metal-free catalytic system that operates under ambient conditions for the N-methylation of amines. The methylation of amines with CO2 as C1 source and Ph2SiH2 as reducing agent was achieved with an N-heterocyclic carbene (NHC) as the catalyst. The catalyst is tolerant toward a variety of functional groups (including esters and ethers, nitro, nitrile, and carbonyl groups, and unsaturated C-C bonds); the reaction uses commercially available reagents and can be performed on a gram scale.
- Das, Shoubhik,Bobbink, Felix D.,Laurenczy, Gabor,Dyson, Paul J.
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supporting information
p. 12876 - 12879
(2016/02/18)
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- General catalytic methylation of amines with formic acid under mild reaction conditions
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A general catalytic protocol for the methylation of amines has been developed applying, for the first time, formic acid as the C1 building block and silanes as reducing agents. A broad range of aromatic and aliphatic, both primary and secondary, amines has been converted to the corresponding tertiary amines including [N-13C]-labelled drugs in good to excellent yields under mild conditions. Methylation made easy: A general catalytic protocol for the methylation of amines has been developed applying, for the first time, formic acid as the C1 building block and silanes as reducing agents. A broad range of aromatic and aliphatic, both primary and secondary, amines has been converted to the corresponding tertiary amines, including [N-13C]-labelled drugs, in good to excellent yields at mild conditions (see scheme; dppp=(1,3-bis(diphenylphosphino)propane)).
- Sorribes, Ivan,Junge, Kathrin,Beller, Matthias
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supporting information
p. 7879 - 7883
(2014/07/07)
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- Development of a general non-noble metal catalyst for the benign amination of alcohols with amines and ammonia
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The N-alkylation of amines or ammonia with alcohols is a valuable route for the synthesis of N-alkyl amines. However, as a potentially clean and economic choice for N-alkyl amine synthesis, non-noble metal catalysts with high activity and good selectivity are rarely reported. Normally, they are severely limited due to low activity and poor generality. Herein, a simple NiCuFeOx catalyst was designed and prepared for the N-alkylation of ammonia or amines with alcohol or primary amines. N-alkyl amines with various structures were successfully synthesized in moderate to excellent yields in the absence of organic ligands and bases. Typically, primary amines could be efficiently transformed into secondary amines and N-heterocyclic compounds, and secondary amines could be N-alkylated to synthesize tertiary amines. Note that primary and secondary amines could be produced through a one-pot reaction of ammonia and alcohols. In addition to excellent catalytic performance, the catalyst itself possesses outstanding superiority, that is, it is air and moisture stable. Moreover, the magnetic property of this catalyst makes it easily separable from the reaction mixture and it could be recovered and reused for several runs without obvious deactivation. Copyright
- Cui, Xinjiang,Dai, Xingchao,Deng, Youquan,Shi, Feng
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supporting information
p. 3665 - 3675
(2013/03/29)
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- Borrowing hydrogen in water and ionic liquids: Iridium-catalyzed alkylation of amines with alcohols
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The use of [Cp*IrI2]2 as an efficient catalyst for the alkylation of amines by alcohols in either water or ionic liquid is described. Primary amines are converted into secondary amines, and secondary amines into tertiary amines in the absence of base, and the chemistry has been applied to the synthesis of the analgesic fentanyl. The conversion of primary amines into N-heterocycles by the reaction with diols is also described, along with the N-alkylation of sulfonamides.
- Saidi, Ourida,Blacker, A. John,Lamb, Gareth W.,Marsden, Stephen P.,Taylor, James E.,Williams, Jonathan M. J.
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supporting information; experimental part
p. 1046 - 1049
(2011/03/20)
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- SIGMA-1 RECEPTOR LIGANDS AND METHODS OF USE
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The invention provides compounds of formula I and compositions thereof. The invention further provides methods of using the compounds and compositions. The compounds of the invention can provide high affinity binding to sigma-1 receptors in a mammal. The compounds can exhibit selectivity for the sigma-1 receptor over the sigma-2 receptor. The compounds and compositions of the invention can also be used to treat conditions that involve the sigma-1 receptor, such as addiction, cardiovascular conditions, and cancer, for example, cancer of the breast, lung, prostate, ovarian, colorectal, or the CNS.
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Page/Page column 33-34
(2010/07/10)
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- Demonstration of the existence of intermolecular lone pair...π interaction between alcoholic oxygen and the C6F5 group in organic solvent
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The existence of the intermolecular interaction in CDCl3 between oxygen of MeOH and the C6F5 group is demonstrated. The Royal Society of Chemistry 2009.
- Korenaga, Toshinobu,Shoji, Taeko,Onoue, Kazutaka,Sakai, Takashi
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supporting information; experimental part
p. 4678 - 4680
(2010/01/16)
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- Superelectrophilic intermediates in nitrogen-directed aromatic borylation
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The first examples of borylation under conditions of borenium ion generation from hydrogen-bridged boron cations are described. The observable H-bridged cations are generated by hydride abstraction from N,N-dimethylamine boranes Ar(CH2)nNMe2BH3 using Ph3C+ (C6F5)4B - (TrTPFPB) as the hydride acceptor. In the presence of excess TrTPFPB, the hydrogen-bridged cations undergo internal borylation to afford cyclic amine borane derivatives with n = 1-3. The products are formed as the corresponding cyclic borenium ions according to reductive quenching experiments and 11B and 1H NMR spectroscopy in the case with Ar = C6H5 and n = 1. The same cyclic borenium cation is also formed from the substrate with Ar = o-C6H4SiMe3 via desilylation, but the analogous system with Ar = o-C6H 4CMe3 affords a unique cyclization product that retains the tert-butyl substituent. An ortho-deuterated substrate undergoes cyclization with a product-determining isotope effect of kH/kD 2.8. Potential cationic intermediates have been evaluated using B3LYP/6-31G* methods. The computations indicate that internal borylation from 14a occurs via a C-H insertion transition state that is accessible from either the borenium π complex or from a Wheland intermediate having nearly identical energy. The Ar = o-C6H4SiMe3 example strongly favors formation of the Wheland intermediate, and desilylation occurs via internal SiMe3 migration from carbon to one of the hydrides attached to boron.
- De Vries, Timothy S.,Prokofjevs, Aleksandrs,Harvey, Jeremy N.,Vedejs, Edwin
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supporting information; experimental part
p. 14679 - 14687
(2010/01/06)
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- A process for the rapid removal of dialkylamino-substituents from aromatic rings. Application to the expedient synthesis of (R)-tolterodine
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A range of N,N-dialkylanilines have been successfully converted to the parent substituted benzenes by a novel two-step pathway. The products are obtained in good yields and optical purity of adjacent stereocenters is maintained. This technology has been applied toward the synthesis of (R)-tolterodine.
- Paras, Nick A.,Simmons, Bryon,MacMillan, David W.C.
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experimental part
p. 3232 - 3238
(2009/08/15)
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- Synthesis, crystal structure analysis, and pharmacological characterization of desmethoxy-sila-venlafaxine, a derivative of the serotonin/noradrenaline reuptake inhibitor sila-venlafaxine
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rac-Desmethoxy-sila-venlafaxine (rac-3) is a derivative of the noradrenaline-selective serotonin/noradrenaline reuptake inhibitor rac-sila-venlafaxine (rac-1b), a silicon analogue of the serotonin-selective serotonin/noradrenaline reuptake inhibitor rac-venlafaxine (rac-1a) (rac-1a, rac-1-[2-(dimethylamino)-1-(4-methoxyphenyl)ethyl]cyclohexan-1-ol; rac-1b, rac-1-[2-(dimethylamino)-1-(4-methoxyphenyl)ethyl]-1-silacyclohexan-1-ol ). The synthesis and crystal structure analyses of rac-3 and rac-3 · HCl are reported, and the pharmacological properties of rac-1a, rac-1b, rac-2 (a sila-venlafaxine derivative with a silacyclopentanol skeleton instead of a silacyclohexanol framework), and rac-3 are compared (comparison of the pharmacological selectivity profiles with respect to serotonin, noradrenaline, and dopamine reuptake inhibition).
- Dai?, Jürgen O.,Burschka, Christian,Mills, John S.,Montana, John G.,Showell, Graham A.,Warneck, Julie B.H.,Tacke, Reinhold
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p. 3589 - 3595
(2007/10/03)
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- Efficient synthesis of tertiary amines from secondary amines
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Reliable N-alkylations of secondary amines have been developed. By using DIAD and TPP (or PS-TPP) a variety of secondary amines can be converted to the corresponding tertiary amines in good to excellent yields with diverse alkylhalides; no formation of quaternary amine salts are observed. These protocols are amenable to combinatorial chemistry libraries, and are also useful for the syntheses of secondary amines by an acid lysis of the cleavable tertiary amino resins.
- Kurosu, Michio,Dey, Sevendu Sekhar,Crick, Dean C.
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p. 4871 - 4875
(2007/10/03)
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- Synthesis of methyl carbamates from primary aliphatic amines and dimethyl carbonate in supercritical CO2: Effects of pressure and cosolvents and chemoselectivity
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(Chemical Equation Presented) At 130 °C, in the presence of CO 2 (5-200 bar), primary aliphatic amines react with dimethyl carbonate (MeOCO2Me, DMC) to yield methyl carbamates (RNHCO2Me) and N-methylation side-products (RNHMe and RNMe2). The pressure of CO2 largely influences both the reaction conversion and the selectivity toward urethanes: in general, conversion goes through a maximum (70-80%) in the midrange (40 bar) and drops at lower and higher pressures, whereas selectivity is continuously improved (from 50% up to 90%) by an increase of the pressure. This is explained by the multiple role of CO2 in (i) the acid/base equilibrium with aliphatic amines, (ii) the reactivity/solubility of RNHCO2- nucleophiles with/in DMC, and (iii) the inhibition of competitive N-methylation reaction of the substrates. Cosolvents also affect the reaction: in particular, a drop in selectivity is observed with polar protic media (i.e., MeOH), plausibly because of solvation effects (through H-bonds) of RNHCO2- moieties. The reaction shows also a good chemoselectivity: bifunctional aliphatic amines bearing either aromatic NH2 or OH substituents [XC6H4(CH2)nNH2, X = NH2, OH; n = 1 2], undergo methoxycarbonylation reactions exclusively at aliphatic amino groups and give the corresponding methyl carbamates [XC 6H4(CH2)nNHCO2Me] in 39-65% isolated yields.
- Selva, Maurizio,Tundo, Pietro,Perosa, Alvise,Dall'Acqua, Federico
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p. 2771 - 2777
(2007/10/03)
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- Selective N-methylation of primary aliphatic amines with dimethyl carbonate in the presence of alkali cation exchanged Y-faujasites
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The N-methylation of aliphatic amines [XC6H4(CH 2)nNH2; n=1, X=H (1a), o-MeO (1b), p-MeO (1c); n=2, X=H (2a), o-MeO (2b); 1d: PhCH(Me)NH2] with dimethyl carbonate (DMC) is efficiently catalysed by NaY faujasite: on condition that CO 2 (a co-product of the reaction) is carefully removed, N-methyl- and N,N-dimethyl-amines (RNHMe and RNMe2) are obtained in good overall yields (70-90%). Otherwise, in the presence of CO2, carbamates (RNHCO2Me) form competitively to a large extent. The reaction probably proceeds through a BAl2 displacement of the amine on DMC.
- Selva, Maurizio,Tundo, Pietro
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p. 8139 - 8142
(2007/10/03)
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- Efficient Cs2CO3-promoted solution and solid phase synthesis of carbonates and carbamates in the presence of TBAI
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Novel solution and solid-phase methods for the synthesis of carbonates and carbamates were developed using cesium bases and TBAI via a three-component coupling. Cesium carbonate not only promoted successful carbonylations of alcohols and carbamations of amines, but also suppressed common side reactions traditionally seen using existing protocols. Various alcohols and amines were examined, using a wide array of alkyl halides, and the results demonstrated this methodology was highly chemoselective. In particular, use of either sterically demanding substrates or amino acid derivatives afforded the corresponding products exclusively, offering a wide variety of applications such as novel protecting groups and peptidomimetic syntheses.
- Salvatore, Ralph N,Chu, Feixia,Nagle, Advait S,Kapxhiu, Elona A,Cross, Richard M,Jung, Kyung Woon
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p. 3329 - 3347
(2007/10/03)
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- A high throughput synthesis of N,N-dimethyl tertiary amines
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N,N-dimethyl tertiary amines are obtained in high yields by titanium(IV) isopropoxide mediated reductive amination of carbonyl compounds with a commercially available methanol solution of dimethylamine.
- Bhattacharyya, Sukanta
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p. 2001 - 2008
(2007/10/03)
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- Zwitterionic sulfobetaine inhibitors of squalene synthase
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A substantial number of sulfobetaines (e.g., 10) have been synthesized and evaluated as inhibitors of squalene synthase (SS) on the basis of the idea that their zwitterionic structure would have properties conducive both to binding in the active site and to passage through cell membranes. When the simple sulfobetaine moiety is incorporated into compounds containing hydrophobic portions like those in farnesyl diphosphate (1) or presqualene diphosphate (2), inhibition of SS in a rat liver microsomal assay was indeed observed. For example, farnesylated sulfobetaine 10 has IC50 = 10 μM and aromatic derivative 35 has IC50 = 2 μM for SS inhibition. A wide variety of structural modifications, exemplified by compounds 43, 52, 76, 85, 91, 99, 111, and 115, was investigated. Unfortunately, no inhibitors in the submicromolar range were discovered, and exploration of a different type of zwitterion seems necessary if this appealing approach to inhibition of SS is going to provide a potential antihypercholesterolemic agent.
- Spencer, Thomas A.,Onofrey, Thomas J.,Cann, Reginald O.,Russel, Jonathon S.,Lee, Laura E.,Blanchard, Daniel E.,Castro, Alfredo,Gu, Peide,Jiang, Guojian,Shechter, Ishaiahu
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p. 807 - 818
(2007/10/03)
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- Further studies of intramolecular motions in crystalline ammonium bromides by CP/MAS NMR
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A series of nine compounds consisting of dimethyl, trimethyl and ethyldimethyl ammonium bromides in which the other alkyl group contains a (2-phenyl)ethyl moiety were synthesised and studied by CP/MAS NMR. The results of dynamic NMR studies on the solids suggest that there is a dramatically wide range of molecular motions occurring in this simple series of compounds. A combination of dynamic line shape analyses and Τ1ρ measurements reveals the considerable extent of intramolecular group motions including rotations of trimethylammonium, ethyldimethylammonium and phenyl groups. Rates of rotation and activation parameters for these molecular motions are derived where appropriate.
- Riddell, Frank G.,Rogerson, Martin
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p. 249 - 255
(2007/10/03)
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- Carbamate linkers as latent N-methylamines in solid phase synthesis
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A new linker strategy for solid phase synthesis has been developed. It utilizes LAH reduction of a carbamate connection to Wang resin which results in N-methylamines, a useful functionality in medicinal chemistry.
- Ho, Chih Y.,Kukla, Michael J.
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p. 2799 - 2802
(2007/10/03)
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- Borohydride reductions in dichloromethane: A convenient, environmentally compatible procedure for the methylation of amines
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The combination of zinc chloride and sodium borohydride in dichloromethane is used to effect reductive aminations of formaldehyde with a variety of primary and secondary amines containing potentially acid-sensitive functional groups in good to excellent yields.
- Bhattacharyya
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p. 2061 - 2069
(2007/10/02)
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- One-pot Synthesis of Secondary or Tertiary Amines from Alcohols and Amines via Alkoxyphosphonium Salts
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Secondary or tertiary amines may be prepared from primary alcohols and primary or secondary amines by treating triphenylphosphine with N-bromosuccinimide (NBS) in the presence of the alcohol at low temperature, followed by addition of the amine and heating for about 1 h.The yield of amine is good to fair, decreasing sharply with sterically congested alcohols and starting amines.
- Froyen, Paul,Juvvik, Paul
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p. 9555 - 9558
(2007/10/02)
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- Transformation of Monoamine Oxidase-B Primary Amine Substrates into Time-Dependent Inhibitors. Tertiary Amine Homologues of Primary AMine Substrates
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A family of N-methylated and N,N-dimethylated alkyl and arylalkylamines was prepared and more than half of the analogues were shown to be time-dependent pseudo-first-order inhibitors of monoamine oxidase-B.Some of the time-dependent inactivators were reversible and others were irreversible with respect to prolonged dialysis following inactivation.Partition ratios ranged from zero to 11 000.These results are rationalized in terms of a combination of an inductive effect and a stereoelectronic effect as a result of hindered rotation of an active site covalent adduct.A molecualr mechanics calculation indicates that there is at least 10 kcal/mol of torsional energy to be overcome in order for the enzyme adduct to be released.These findings show that tertiary amine homologues of primary amine substrates of monoamino oxidase are time-dependent inhibitors, and this should be useful in the design of new inactivators of this enzyme.
- Ding, Charles Z.,Lu, Xingliang,Nishimura, Kuniko,Silverman, Richard B.
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p. 1711 - 1715
(2007/10/02)
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- Base-promoted elimination reactions of acetaldehyde N-alkyl-N,N-dimethylhydrazonium salts. A convenient synthesis of N,N-dimethylalkylamines
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The title reaction was utilized for efficient conversion of S(N)2-reactive alkyl halides to the corresponding N,N-dimethylalkylamines.
- Smith,Marcucci,Tingue
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p. 381 - 389
(2007/10/02)
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