727733-92-8Relevant articles and documents
Late-Stage N-Me Selective Arylation of Trialkylamines Enabled by Ni/Photoredox Dual Catalysis
Shen, Yangyang,Rovis, Tomislav
supporting information, p. 16364 - 16369 (2021/10/21)
The diversity and wide availability of trialkylamines render them ideal sources for rapid construction of complex amine architectures. Herein, we report that a nickel/photoredox dual catalysis strategy affects site-selective α-arylation of various trialkylamines. Our catalytic system shows exclusive N-Me selectivity with a wide range of trialkylamines under mild conditions, even in the context of late-stage arylation of pharmaceutical compounds bearing this common structural motif. Mechanistic studies indicate the unconventional behavior of Ni catalyst upon intercepting the α-amino radicals, in which only the primary α-amino radical undergoes a successful cross-coupling process.
Modular, Self-Assembling Metallaphotocatalyst for Cross-Couplings Using the Full Visible-Light Spectrum
Reischauer, Susanne,Strauss, Volker,Pieber, Bartholom?us
, p. 13269 - 13274 (2020/12/03)
The combination of nickel and photocatalysis has unlocked a variety of cross-couplings. These protocols rely on a few photocatalysts that can only convert a small portion of visible light (500 nm) into chemical energy. The high-energy photons that excite
Direct Catalytic Decarboxylative Amination of Aryl Acetic Acids
Kong, Duanyang,Moon, Patrick J.,Bsharat, Odey,Lundgren, Rylan J.
supporting information, p. 1313 - 1319 (2019/12/15)
The decarboxylative coupling of a carboxylic acid with an amine nucleophile provides an alternative to the substitution of traditional organohalide coupling partners. Benzoic and alkynyl acids may be directly aminated by oxidative catalysis. In contrast, methods for intermolecular alkyl carboxylic acid to amine conversion, including amidate rearrangements and photoredox-promoted approaches, require stoichiometric activation of the acid unit to generate isocyanate or radical intermediates. Reported here is a process for the direct chemoselective decarboxylative amination of electron-poor arylacetates by oxidative Cu catalysis. The reaction proceeds at (or near) room temperature, uses native carboxylic acid starting materials, and is compatible with protic, electrophilic, and other potentially complicating functionality. Mechanistic studies support a pathway in which ionic decarboxylation of the acid generates a benzylic nucleophile which is aminated in a Chan–Evans–Lam-type process.
Development of inhibitors against mycobacterium abscessus tRNA (m1G37) Methyltransferase (TrmD) Using Fragment-Based Approaches
Whitehouse, Andrew J.,Thomas, Sherine E.,Brown, Karen P.,Fanourakis, Alexander,Chan, Daniel S.-H.,Libardo, M. Daben J.,Mendes, Vitor,Boshoff, Helena I. M.,Floto, R. Andres,Abell, Chris,Blundell, Tom L.,Coyne, Anthony G.
supporting information, p. 7210 - 7232 (2019/08/20)
Mycobacterium abscessus (Mab) is a rapidly growing species of multidrug-resistant nontuberculous mycobacteria that has emerged as a growing threat to individuals with cystic fibrosis and other pre-existing chronic lung diseases. Mab pulmonary infections are difficult, or sometimes impossible, to treat and result in accelerated lung function decline and premature death. There is therefore an urgent need to develop novel antibiotics with improved efficacy. tRNA (m1G37) methyltransferase (TrmD) is a promising target for novel antibiotics. It is essential in Mab and other mycobacteria, improving reading frame maintenance on the ribosome to prevent frameshift errors. In this work, a fragment-based approach was employed with the merging of two fragments bound to the active site, followed by structure-guided elaboration to design potent nanomolar inhibitors against Mab TrmD. Several of these compounds exhibit promising activity against mycobacterial species, including Mycobacterium tuberculosis and Mycobacterium leprae in addition to Mab, supporting the use of TrmD as a target for the development of antimycobacterial compounds.
Photoredox-catalyzed Direct Reductive Amination of Aldehydes without an External Hydrogen/Hydride Source
Alam, Rauful,Molander, Gary A.
supporting information, p. 2680 - 2684 (2018/05/22)
The direct reductive amination of aromatic aldehydes has been realized using a photocatalyst under visible light irradiation. The single electron oxidation of an in situ formed aminal species generates the putative α-amino radical that eventually delivers the reductive amination product. This method is operationally simple, highly selective, and functional group tolerant, which allows the direct synthesis of benzylic amines by a unique mechanistic pathway.
Noble metal-free upgrading of multi-unsaturated biomass derivatives at room temperature: Silyl species enable reactivity
Li, Hu,Zhao, Wenfeng,Dai, Wenshuai,Long, Jingxuan,Watanabe, Masaru,Meier, Sebastian,Saravanamurugan, Shunmugavel,Yang, Song,Riisager, Anders
, p. 5327 - 5335 (2018/12/05)
Biomass derivatives are a class of oxygen-rich organic compounds, which can be selectively upgraded to various value-added molecules by partial or complete hydrogenation over metal catalysts. Here, we show that Cs2CO3, a low-cost commercial chemical, enables the selective reduction of dicarbonyl compounds including bio-derived carboxides to monohydric esters/amides, hydroxylamines or diols with high yields (82-99%) at room temperature using eco-friendly and equivalent hydrosilane as a hydride donor. The in situ formation of silyl ether enables the developed catalytic system to tolerate other unsaturated groups and permits a wide substrate scope with high selectivities. Spectroscopic and computational studies elucidate reaction pathways with an emphasis on the role of endogenous siloxane.
Structural-based design, synthesis, and antitumor activity of novel alloxazine analogues with potential selective kinase inhibition
Malki, Waleed H.,Gouda, Ahmed M.,Ali, Hamdy E.A.,Al-Rousan, Rabaa,Samaha, Doaa,Abdalla, Ashraf N.,Bustamante, Juan,Abd Elmageed, Zakaria Y.,Ali, Hamed I.
, p. 31 - 52 (2018/04/26)
Protein kinases are promising therapeutic targets for cancer therapy. Here, we applied multiple approaches to optimize the potency and selectivity of our reported alloxazine scaffold. Flexible moieties at position 2 of the hetero-tricyclic system were inc
Mild and selective Et2Zn-catalyzed reduction of tertiary amides under Hydrosilylation conditions
Kovalenko, Oleksandr O.,Volkov, Alexey,Adolfsson, Hans
supporting information, p. 446 - 449 (2015/03/05)
Diethylzinc (Et2Zn) can be used as an efficient and chemoselective catalyst for the reduction of tertiary amides under mild reaction conditions employing cost-effective polymeric silane (PMHS) as the hydride source. Crucial for the catalytic activity was the addition of a substoichiometric amount of lithium chloride to the reaction mixture. A series of amides containing different additional functional groups were reduced to their corresponding amines, and the products were isolated in good-to-excellent yields.
Exploration of the nicotinamide-binding site of the tankyrases, identifying 3-arylisoquinolin-1-ones as potent and selective inhibitors in vitro
Paine, Helen A.,Nathubhai, Amit,Woon, Esther C.Y.,Sunderland, Peter T.,Wood, Pauline J.,Mahon, Mary F.,Lloyd, Matthew D.,Thompson, Andrew S.,Haikarainen, Teemu,Narwal, Mohit,Lehti?, Lari,Threadgill, Michael D.
supporting information, p. 5891 - 5908 (2015/11/11)
Tankyrases-1 and -2 (TNKS-1 and TNKS-2) have three cellular roles which make them important targets in cancer. Using NAD+ as a substrate, they poly(ADP-ribosyl)ate TRF1 (regulating lengths of telomeres), NuMA (facilitating mitosis) and axin (in wnt/β-catenin signalling). Using molecular modelling and the structure of the weak inhibitor 5-aminoiso quinolin-1-one, 3-aryl-5-substituted-isoquinolin-1-ones were designed as inhibitors to explore the structure-activity relationships (SARs) for binding and to define the shape of a hydrophobic cavity in the active site. 5-Amino-3-arylisoquinolinones were synthesised by Suzuki-Miyaura coupling of arylboronic acids to 3-bromo-1-methoxy-5-nitro-isoquinoline, reduction and O-demethylation. 3-Aryl-5-methylisoquinolin-1-ones, 3-aryl-5-fluoroisoquinolin-1-ones and 3-aryl-5-methoxyisoquinolin-1-ones were accessed by deprotonation of 3-substituted-N,N,2-trimethylbenzamides and quench with an appropriate benzonitrile. SAR around the isoquinolinone core showed that aryl was required at the 3-position, optimally with a para-substituent. Small meta-substituents were tolerated but groups in the ortho-positions reduced or abolished activity. This was not due to lack of coplanarity of the rings, as shown by the potency of 4,5-dimethyl-3-phenylisoquinolin-1-one. Methyl and methoxy were optimal at the 5-position. SAR was rationalised by modelling and by crystal structures of examples with TNKS-2. The 3-aryl unit was located in a large hydrophobic cavity and the para-substituents projected into a tunnel leading to the exterior. Potency against TNKS-1 paralleled potency against TNKS-2. Most inhibitors were highly selective for TNKSs over PARP-1 and PARP-2. A range of highly potent and selective inhibitors is now available for cellular studies.
Base-promoted N-alkylation using formamides as the N-sources in neat water
Chen, Wen-Xin,Zhang, Cai-Yun,Shao, Li-Xiong
, p. 880 - 885 (2014/01/23)
An efficient catalyst-free, alternative method for the C-N bond formation reaction of alkyl electrophiles using formamides as the N-sources was achieved under mild conditions. The reaction possesses the advantages of a broad range of substrates scope and wide functional group tolerance. It should also be noted that this process was performed using the environmentally benign water as the sole solvent, and high yield can also be achieved in ten-gram scale.
