- Efficient Synthesis of α-Ketothioamides From α-Nitroketones, Amines or DMF and Elemental Sulfur Under Oxidant-Free Conditions
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We have developed a practical, general protocol for denitration of readily available α-nitroketones with sulfur and amines to access a broad range of α-ketothioamides under mild conditions. Such a reaction proceeds under metal-, oxidant-, and catalyst-free conditions to provide synthetically useful α-ketothioamides. Furthermore, the mild reaction conditions tolerate a wide range of substrates especially for the synthesis of aliphatic α-ketothioamides which are rarely reported.
- Zhang, Zhenlei,Yang, Jiusi,Yu, Renjie,Wu, Kairui,Bu, Jiping,Li, Shaoke,Qian, Peng,Sheng, Liangquan
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p. 5209 - 5212
(2021/10/19)
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- Unravelling the allosteric targeting of phgdh at the act-binding domain with a photoactivatable diazirine probe and mass spectrometry experiments
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The serine biosynthetic pathway is a key element contributing to tumor proliferation. In recent years, targeting of phosphoglycerate dehydrogenase (PHGDH), the first enzyme of this pathway, intensified and revealed to be a promising strategy to develop ne
- Dochain, Simon,Feron, Olivier,Frédérick, Rapha?l,Ravez, Séverine,Spillier, Quentin,Thabault, Léopold,Vertommen, Didier
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supporting information
(2021/06/28)
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- Desulfurizing agent for thioamides
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Thioamides treated with thionyl chloride in an ionic liquid were successfully converted into amides.
- Polushina,Zavarzin,Krayushkin,Rodionova,Yarovenko
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p. 383 - 385
(2021/03/03)
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- Structure–activity relationships (SARs) of α- ketothioamides as inhibitors of phosphoglycerate dehydrogenase (PHGDH)
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For many years now, targeting deregulation within cancer cells’ metabolism has appeared as a promising strategy for the development of more specific and efficient cancer treatments. Recently, numerous reports highlighted the crucial role of the serine synthetic pathway, and particularly of the phosphoglycerate dehydrogenase (PHGDH), the first enzyme of the pathway, to sustain cancer progression. Yet, because of very weak potencies usually in cell-based settings, the inhibitors reported so far failed to lay ground on the potential of this approach. In this paper, we report a structure–activity relationship study of a series of α-ketothioamides that we have recently identified. Interestingly, this study led to a deeper understanding of the structure–activity relationship (SAR) in this series and to the identification of new PHGDH inhibitors. The activity of the more potent compounds was confirmed by cellular thermal shift assays and in cell-based experiments. We hope that this research will eventually provide a new entry point, based on this promising chemical scaffold, for the development of therapeutic agents targeting PHGDH.
- Spillier, Quentin,Ravez, Séverine,Unterlass, Judith,Corbet, Cyril,Degavre, Charline,Feron, Olivier,Frédérick, Rapha?l
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- Metal-Free C-N or C-C Bond Cleavages of α-Azido Ketones: An Oxidative-Amidation Strategy for the Synthesis of α-Ketothioamides and Amides
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A novel metal-free oxidative-amidation strategy for the synthesis of α-ketothioamides and amides from α-azido ketones was developed. The C-H bond thionation of α-azido ketones with elemental sulfur could form α-ketothioacyl azide, which was then nucleophilically attacked by amines, causing the cleavage of the C-N bond to afford α-ketothioamides, while amides could be formed with the release of nitrogen gas and cyano anion in the presence of PhI(OAc)2 by selective C-C bond cleavage.
- Yu, Pei,Wang, Yuwei,Zeng, Zhigang,Chen, Yunfeng
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p. 14883 - 14891
(2019/11/11)
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- Alpha-ketothioamide compound and synthesis method thereof
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The invention provides an alpha-ketothioamide compound and a synthesis method thereof. The alpha-ketothioamide compound is obtained by mixing an alpha-azidoacetophenone compound, an amine compound, elemental sulfur and a solvent, reacting for 0.5-4 hours
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Paragraph 0037-0041
(2019/12/10)
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- Synthesis of α-Keto Thioamides by Metal-Free C-C Bond Cleavage in Enaminones Using Elemental Sulfur
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An unprecedented method for cleaving the C-C bond in N,N-disubstituted enaminones in the presence of elemental sulfur and N,N-dimethyl-4-aminopyridine is disclosed. Without using any metal catalyst or additive, the cascade functionalization of both C?C an
- Gan, Lu,Gao, Yong,Wei, Li,Wan, Jie-Ping
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p. 1064 - 1069
(2019/01/24)
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- Methyl ketone break-and-rebuild: A strategy for full α-heterofunctionalization of acetophenones
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The Willgerodt reaction under iron-catalyzed aerobic conditions was found to be an excellent tool for full α-heterofunctionalization of acetophenones with sulfur and amines. Via this break-and rebuild strategy, a wide range of thioglyoxamides was synthesi
- Nguyen, Thanh Binh,Retailleau, Pascal
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supporting information
p. 5371 - 5374
(2017/11/22)
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- α-Ketothioamide Derivatives: A Promising Tool to Interrogate Phosphoglycerate Dehydrogenase (PHGDH)
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Given the putative role of PHGDH in cancer, development of inhibitors is required to explore its function. In this context, we established and validated a straightforward enzymatic assay suitable for high-throughput screening and we identified inhibitors with similar chemical scaffolds. Through a convergent pharmacophore approach, we synthesized α-ketothioamides that exhibit interesting in vitro PHGDH inhibition and encouraging cellular results. These novel probes may be used to understand the emerging biology of this metabolic target.
- Ravez, Séverine,Corbet, Cyril,Spillier, Quentin,Dutu, Alice,Robin, Anita D.,Mullarky, Edouard,Cantley, Lewis C.,Feron, Olivier,Frédérick, Rapha?l
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supporting information
p. 1591 - 1597
(2017/03/08)
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- Synthesis of α-Keto Amides by a Pyrrolidine/TEMPO-Mediated Oxidation of α-Keto Amines
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A mild procedure has been developed for the synthesis of α-keto amides by α-oxidation of the corresponding α-keto amines mediated by pyrrolidine and TEMPO. The method can also be applied to the synthesis of α-keto thioamides and α-keto amidines.
- Yu, Lu,Somfai, Peter
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p. 2587 - 2590
(2016/11/11)
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- Direct synthesis of α-ketothioamides from aryl methyl ketones and amines via I2-promoted sp3 C-H functionalization
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A domino reaction that involves the formation of CS and C-N bonds in one process via sp3 C-H functionalization strategy has been developed. This reaction affords an efficient and direct method for the synthesis of α-ketothioamides from aryl met
- Li, Hong-Zheng,Xue, Wei-Jian,Wu, An-Xin
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p. 4645 - 4651
(2014/06/23)
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- Na2S-mediated thionation: An efficient access to secondary and tertiary α-ketothioamides via Willgerodt-Kindler reaction of readily available arylglyoxals with amines
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The task of this paper is to provide an efficient process for synthesis of secondary and tertiary α-ketothioamides via Willgerodt-Kindler reaction of readily available arylglyoxals with amines using Na2S as an effective catalyst. A plausible role for Na2S in the reaction of arylglyoxals with primary amines is proposed.
- Saeidian, Hamid,Vahdati-Khajehi, Saleh,Bazghosha, Homeira,Mirjafary, Zohreh
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p. 700 - 710
(2015/10/19)
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- Reactions of diphenacylaniline and diphenacyl sulfide under Gewald conditions: Generation of enamines and thioamides
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The 1,5-diketone, diphenacylaniline, yielded an enamine under Gewald conditions, while another 1,5-diketone, diphenacyl sulfide, resulted in thioamide formation under identical conditions. 2-Amino-4-(3-oxo-1,3- diphenylpropyl)-4,5,6,7-tetrahydrobenzo[b]th
- Paul, Nidhin,Sathishkumar, Ramalingam,Anuba, Chellathurai,Muthusubramanian, Shanmugam
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p. 7445 - 7451
(2013/06/27)
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- Synthesis of α-ketothioamides via willgerodt-kindler reaction of arylglyoxals with amines and sulfur under solvent-free conditions
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Willgerodt-Kindler reaction of arylglyoxal hydrates with secondary amines and elemental sulfur under solvent-free conditions at 80 °C is developed, in which α-ketothioamides are obtained in 70-90% yield in 0.6-1 hour. The X-ray crystal-structure analysis for one compound was obtained. Georg Thieme Verlag Stuttgart . New York.
- Eftekhari-Sis, Bagher,Khajeh, Saleh Vahdati,Büyükgüng?r, Orhan
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p. 977 - 980
(2013/06/27)
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- Willgerodt-Kindler reaction of arylglyoxals with amines and sulfur in aqueous media: A simple and efficient synthesis of -ketothioamides
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A simple and efficient method for the synthesis of -ketothioamides via the Willgerodt-Kindler reaction is developed. Reactions were carried out between arylglyoxal hydrates, amines and elemental sulfur in water at 80°C to afford corresponding -ketothioamides in good to high yields in a short reaction time.
- Eftekhari-Sis, Bagher,Vahdati-Khajeh, Saleh,Amini, S. Motahhareh,Zirak, Maryam,Saraei, Mahnaz
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p. 464 - 473
(2013/10/21)
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- A study of the Willgerodt-Kindler reaction to obtain thioamides and α-ketothioamides under solvent-less conditions
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In this paper, the results obtained in the synthesis of thioamides and α-ketothioamides by a modification of the Willgerodt-Kindler reaction, under solvent-free and noncatalyst conditions using IR energy as a source of activation, are presented. The use of IR energy in these reactions has been shown to lead to a mixture of thioamide and α-ketothioamide as the main products in most cases, with the latter predominating. The yields of α-ketothioamides from most of these reactions are better than those reported previously. To the best of our knowledge, this is the first time that IR energy has been applied to promote the Willgerodt-Kindler reaction.
- Valdez-Rojas, Jose Ernesto,Rios-Guerra, Hulme,Ramirez-Sanchez, Alma Leticia,Garcia-Gonzalez, Guadalupe,Alvarez-Toledano, Cecilio,Lopez-Cortes, Jose Guadalupe,Toscano, Ruben A.,Penieres-Carrillo, Jose Guillermo
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supporting information; experimental part
p. 567 - 573
(2012/08/08)
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- A facile aerobic copper-catalyzed α-oxygenation of aryl thioacetamides: An efficient access to α-keto aryl thioamides
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Copper(II) efficiently catalyzes the aerobic oxidation of aryl thioacetamides into the corresponding α-keto aryl thioamides in moderate to high yields in the presence of K2CO3 under O 2 atmosphere. This protocol is simple, clean, and generates water as the only byproduct. A mechanism is proposed for the reaction course. Georg Thieme Verlag Stuttgart.
- Moghaddam, Firouz Matloubi,Mirjafary, Zohreh,Saeidian, Hamdollah,Javan, Marjan Jebeli
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p. 892 - 896
(2008/12/22)
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- Synthesis of phenylthioacetomorpholide: Effect of substrate on the Willgerodt-Kindler reaction
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The effect of substrates on the Willgerodt-Kindler reaction was studied. The existence of acidic protons on these substrates accerelates the formation of thiomorpholide was found.
- Darabi, Hossein Reza,Aghapoor, Kioumars,Tabar-Heydar, Kourosh,Nooshabadi, Masoud
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p. 1189 - 1192
(2007/10/03)
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- Optimum Conditions for the Willgerodt-Kindler Reaction 2: A Multivariate Study of the Influence of Different Solvents on the Optimum Reaction Conditions
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The optimum conditions for synthesis of phenylacetic acid thiomorpholide by the reaction of acetophenone in the presence of morpholine and elemental sulfur have been studied in 13 solvents: N,N-dimethylformamide, triethylene glycol, N-methylacetamide, eth
- Carlson, Rolf,Lundstedt, Torbjoern,Shabana, Rashad
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p. 694 - 699
(2007/10/02)
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