- An efficient approach for the synthesis of new (±)-coixspirolactams
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Coixspirolactams, spiro[oxindole-γ-lactones], are found in adlay seeds and exhibit anticancer activity. A novel synthetic methodology was developed to enable an easy access to (±)-coixspirolactam A and a large number of new coixspirolactams in excellent overall yields. The exquisite exploitation of formamide reactivity was essential for the construction of oxindole and lactone scaffolds. This journal is
- Nascimento, Vinicius R.,Suenaga, Melissa L. S.,Andrade, Leandro H.
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p. 5458 - 5465
(2020/08/03)
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- Disulfide Promoted C?P Bond Cleavage of Phosphoramide: “P” Surrogates to Synthesize Phosphonates and Phosphinates
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A metal-free C?P bond cleavage reaction is described herein. Phosphoramides, a phosphine source, can react with alcohols to produce phosphonate and phosphinate derivatives in the presence of a disulfide. P?H2, P-alkyl, and P,P-dialkyl phosphoramides can be used as substrates to obtain the corresponding pentavalent phosphine products. (Figure presented.).
- Hou, Fei,Du, Xing-Peng,Alduma, Anwar I.,Li, Zhi-Feng,Huo, Cong-De,Wang, Xi-Cun,Wu, Xiao-Feng,Quan, Zheng-Jun
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supporting information
p. 4755 - 4760
(2020/10/06)
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- Rh(i)-Catalyzed regioselective arylcarboxylation of acrylamides with arylboronic acids and CO2
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The first Rh(i)-catalyzed regioselective arylcarboxylation of electron-deficient acrylamides with arylboronic acids under atmospheric pressure of CO2 has been developed. A range of acrylamides and arylboronic acids were compatible with this reaction under redox-neutral conditions, leading to a series of malonate derivatives that are versatile building blocks in organic syntheses.
- Cai, Lei,Fu, Lei,Gao, Yuzhen,Li, Gang,Li, Shangda,Zhou, Chunlin
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supporting information
p. 7328 - 7332
(2020/11/19)
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- Metal-Free C–S Bond Cleavage to Access N-Substituted Acrylamide and β-Aminopropanamide
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Metal-free and Selectfluor-mediated C–S bond cleavage is described. This novel strategy provides a facile and efficient method to access important N-substituted acrylamide and β-aminopropanamide derivatives with good functional group tolerance and yields.
- Yang, Ke,Li, Yi,Ma, Zhiyan,Tang, Long,Yin, Yue,Zhang, Hao,Li, Zhengyi,Sun, Xiaoqiang
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p. 5812 - 5814
(2019/08/27)
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- Systematic study of the glutathione (GSH) reactivity of N-arylacrylamides: 1. Effects of aryl substitution
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Success in the design of targeted covalent inhibitors depends in part on a knowledge of the factors influencing electrophile reactivity. In an effort to further develop an understanding of structure-reactivity relationships among N-arylacrylamides, we determined glutathione (GSH) reaction rates for a family of N-arylacrylamides independently substituted at ortho-, meta-, and para-positions with 11 different groups common to inhibitor design. We find that substituent effects on reaction rates show a linear Hammett correlation for ortho-, meta-, and para-substitution. In addition, we note a correlation between 1H and 13C NMR chemical shifts of the acrylamide with GSH reaction rates, suggesting that NMR chemical shifts may be a convenient surrogate measure of relative acrylamide reactivity. Density functional theory calculations reveal a correlation between computed activation parameters and experimentally determined reaction rates, validating the use of such methodology for the screening of synthetic candidates in a prospective fashion.
- Cee, Victor J.,Volak, Laurie P.,Chen, Yuping,Bartberger, Michael D.,Tegley, Chris,Arvedson, Tara,McCarter, John,Tasker, Andrew S.,Fotsch, Christopher
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p. 9171 - 9178
(2015/12/23)
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- Cascade synthesis of spirooxindole δ-lactone derivatives through N-aryl hydroxymethylacrylamides with xanthates
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A novel and highly efficient cascade synthesis of spirooxindole δ-lactone derivatives from N-aryl hydroxymethylacrylamides and xanthates in good yields is described. The reaction proceeds through a radical addition/cyclization and ester exchange, in which two new C-C bonds and one C-O bond were formed.
- Wang, Shucheng,Huang, Xuhu,Wen, Yanzhao,Ge, Zemei,Wang, Xin,Li, Runtao
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supporting information
p. 8117 - 8122
(2015/12/30)
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- Ligand-free CuTC-catalyzed N-arylation of amides, anilines and 4-aminoantipyrine: Synthesis of N-arylacrylamides, 4-amido-N-phenylbenzamides and 4-amino(N-phenyl)antipyrenes
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N-Arylation of amides and anilines with aryl iodides was efficiently catalyzed by copper thiophenecarboxylate under ligand-free conditions with good to excellent yields. A variety of substituted aryl iodides, amides, anilines and 4-aminoantipyrine were found to be applicable to the simple catalytic system. Furthermore, some practical, unique secondary amides, such as N-arylacrylamides and 4-amido-N-phenylbenzamides, and 4-amino(N-phenyl)antipyrenes, which are difficult to obtain by the classical methods, were prepared.
- Quan, Zheng-Jun,Xia, Hai-Dong,Zhang, Zhang,Da, Yu-Xia,Wang, Xi-Cun
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- Promiscuity and selectivity in covalent enzyme inhibition: A systematic study of electrophilic fragments
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Covalent ligand-target interactions offer significant pharmacological advantages. However, off-target reactivity of the reactive groups, which usually have electrophilic properties, must be minimized, and the selectivity of irreversible inhibitors is a crucial requirement. We therefore performed a systematic study to determine the selectivity of several electrophilic groups that can be used as building blocks for covalently binding ligands. Six reactive groups with modulated electrophilicity were combined with 11 nonreactive moieties, resulting in a small combinatorial library of 72 fragment-like compounds. These compounds were screened against a group of 11 enzyme targets to assess their selectivity and their potential for promiscuous binding to proteins. The assay results showed a considerably lower degree of promiscuity than initially expected, even for those members of the screening collection that contain supposedly highly reactive electrophiles.
- J?st, Christian,Nitsche, Christoph,Scholz, Therese,Roux, Lionel,Klein, Christian D.
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supporting information
p. 7590 - 7599
(2014/12/11)
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- An efficient copper-catalyzed N-arylation of amides: Synthesis of N-arylacrylamides and 4-amido-N-phenylbenzamides
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Copper-catalyzed intermolecular C-N bond-forming reactions between aryl iodides and amides are described using sodium ascorbate, which is both cheap and nontoxic, as the additive. A variety of functionalized amides including some practical, unique secondary amides, such as N-arylacrylamides and 4-amido-N-phenylbenzamides, which are difficult to obtain by the classical methods, are prepared. Furthermore, some tertiary amides are prepared by using copper thiophenecarboxylate.
- Quan, Zheng-Jun,Xia, Hai-Dong,Zhang, Zhang,Da, Yu-Xia,Wang, Xi-Cun
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p. 8368 - 8374
(2013/09/02)
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- Efficient copper-catalyzed Michael addition of acrylic derivatives with primary alcohols in the presence of base
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A novel and efficient copper-catalyzed Michael addition of acrylic derivatives with primary alcohols in the presence of base has been developed. The protocol uses readily available acrylic derivatives and primary alcohols as the starting materials, inexpensive CuCl2 as the catalyst, and the corresponding addition products were obtained in moderate to excellent yields.
- Wang, Feng,Yang, Haijun,Fu, Hua,Pei, Zhichao
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supporting information
p. 517 - 519
(2013/02/23)
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- Metal-free oxidative spirocyclization of hydroxymethylacrylamide with 1,3-dicarbonyl compounds: A new route to spirooxindoles
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A metal-free oxidative spirocyclization of hydroxymethylacrylamide with 1,3-dicarbonyl compounds is described. The reaction proceeds through tandem dual C-H functionalization and intramolecular dehydration, in which two new C-C bonds and one C-O bond were formed. This method affords a novel and straightforward access to various spirooxindoles under mild conditions.
- Wang, Hua,Guo, Li-Na,Duan, Xin-Hua
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supporting information
p. 5254 - 5257
(2013/11/06)
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- Synthetic transformations of higher terpenoids: XXXII.*synthesis of 16-alkenyl-substituted labdatrienes by oxidative coupling of methyl phlomisoate with alkenes
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Reactions of methyl phlomisoate with methyl acrylate, phenyl acrylate, methyl vinyl ketone, phenyl vinyl ketone, or N-substituted acrylamides catalyzed by Pd(OAc)2 in the presence of Cu(OAc)2, p-benzoquinone in the mixture of propionic acid and acetonitrile proceed regio- and stereoselectively with the formation of (E)- 16-vinyl labdatrienoates. The oxidative coupling under these conditions of the methyl phlomisoate with styrene results in a mixture of 15,16-distyryl-, 16-styryl-, and 16-(1-phenylvinyl)-derivatives of furanolabdanoid. Pleiades Publishing, Ltd., 2013.
- Kharitonov,Kremenko,Shults,Shakirov,Tolstikov
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p. 1690 - 1702
(2014/02/14)
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- Discovery and structure-activity relationship of potent and selective covalent inhibitors of transglutaminase 2 for Huntington's disease
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Tissue transglutaminase 2 (TG2) is a multifunctional protein primarily known for its calcium-dependent enzymatic protein cross-linking activity via isopeptide bond formation between glutamine and lysine residues. TG2 overexpression and activity have been found to be associated with Huntington's disease (HD); specifically, TG2 is up-regulated in the brains of HD patients and in animal models of the disease. Interestingly, genetic deletion of TG2 in two different HD mouse models, R6/1 and R6/2, results in improved phenotypes including a reduction in neuronal death and prolonged survival. Starting with phenylacrylamide screening hit 7d, we describe the SAR of this series leading to potent and selective TG2 inhibitors. The suitability of the compounds as in vitro tools to elucidate the biology of TG2 was demonstrated through mode of inhibition studies, characterization of druglike properties, and inhibition profiles in a cell lysate assay.
- Prime, Michael E.,Andersen, Ole A.,Barker, John J.,Brooks, Mark A.,Cheng, Robert K. Y.,Toogood-Johnson, Ian,Courtney, Stephen M.,Brookfield, Frederick A.,Yarnold, Christopher J.,Marston, Richard W.,Johnson, Peter D.,Johnsen, Siw F.,Palfrey, Jordan J.,Vaidya, Darshan,Erfan, Sayeh,Ichihara, Osamu,Felicetti, Brunella,Palan, Shilpa,Pedret-Dunn, Anna,Schaertl, Sabine,Sternberger, Ina,Ebneth, Andreas,Scheel, Andreas,Winkler, Dirk,Toledo-Sherman, Leticia,Beconi, Maria,MacDonald, Douglas,Mu?oz-Sanjuan, Ignacio,Dominguez, Celia,Wityak, John
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p. 1021 - 1046
(2012/04/10)
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- Synthesis of [11C]/[13C]acrylamides by palladium-mediated carbonylation
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Two methods are presented for the synthesis of acrylamides labelled with 11C (β+, t1/2 = 20.4 min) and 13C in the carbonyl position. In the first method, [1- 11C]acrylic acid is synthesised from [11C]carbon monoxide by palladium-mediated hydroxycarbonylation of acetylene. The labelled carboxylic acid is converted into the acyl chloride and subsequently treated with amine to yield N-benzyl[carbonyl-11C]acrylamide. The second method utilizes [11C]carbon monoxide in a palladium-mediated carbonylative cross-coupling of vinyl halides and amines. A higher radiochemical yield is achieved with the latter method and the amount of amine needed is decreased to 1/20. The 11C-labelled acrylamides were isolated in up to 81 % decay-corrected radiochemical yield. Starting from 10 ± 0.5 GBq of [ 11C]carbon monoxide, N-benzyl[carbonyl-11C]acrylamide was obtained in 4 min with a specific radioactivity of 330 ± 4 GBq μmol-1. Co-labelling with 11C and 13C enabled confirmation of the labelled position by 13C NMR spectroscopy. Wiley-VCH Verlag GmbH & Co. KGaA, 2007.
- Eriksson, Jonas,Aberg, Ola,Langstroem, Bengt
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p. 455 - 461
(2008/02/03)
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- Unique tandem heck-lactamization naphthyridinone ring formation between acrylanilides and halogenated pyridines
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The Heck coupling of acrylanilides with 4-bromo-2-chloro-3-iodo-pyridine using palladium acetate can produce bis-Heck products or undergo an unusual tandem Heck-lactamization ring formation to generate 5-chloro-1-aryl-1,6- naphthyridin-2(1H)-ones.
- Cvetovich, Raymond J.,Reamer, Robert A.,DiMichele, Lisa,Chung, John Y. L.,Chilenski, Jennifer R.
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p. 8610 - 8613
(2007/10/03)
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- Formation of acrylanilides, acrylamides, and amides directly from carboxylic acids using thionyl chloride in dimethylacetamide in the absence of bases
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A general one-pot procedure is described that rapidly converts acrylic acid to anilides upon sequential treatment of the acid in dimethylacetamide (DMAC) with thionyl chloride and stoichiometric amounts of anilines in 88-98% yields, with DMAC offering rate and stability advantages over the use of DMF. The use of DMAC was extended to other organic acids in forming anilides. Benzylamine amides can also be formed using stoichiometric amounts of benzylamine and brought to completion by warming in the absence of additional base. In addition, it was shown that tert-butylamides can be easily formed with the addition of excess tert-butylamine at 20 °C.
- Cvetovich, Raymond J.,DiMichele, Lisa
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p. 944 - 946
(2012/12/23)
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- A novel method for the synthesis of α,β-unsaturated amides mediated by Samarium diiodide
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Promoted by Samarium diiodide (SmI2), α,β-unsaturated amides were formed from nitrogenanions (formed in situ by the reduction of nitro compounds) and αβ-unsaturated esters. This reaction contrasts with the conjugate addition between amines and α,β-unsaturated esters promoted by samarium triiodide (SmI3) and provides an alternative attractive way to obtain α,β-unsaturated amides using SmI 2.
- Zhu, Chun-Lan,Wang, Xia-Xia
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p. 953 - 955
(2007/10/03)
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- Solid-phase synthesis of 2-alkenamides from polystyrene-supported α-selenocarboxylic acids
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The polystyrene-supported α-selenoacetic acid and α-selenopropionic acid were prepared and used for the synthesis of 2-alkenamides from primary and secondary amines in good yields and high purities.
- Liu, Xiao-Ling,Wang, Xing-Cong,Sheng, Shou-Ri
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p. 1303 - 1306
(2007/10/03)
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- Solid-phase synthesis of acrylamides with polymer-bound 2-sulfonylpropanoic acid
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A novel polystyrene-bound 2-sulfonylpropanoic acid has been developed and applied to convenient, traceless synthesis of acrylamides in good yield and purity.
- Sheng, Shou-Ri,Zhou, Wei,Sang, Xiao-Yan,Liu, Xiao-Ling,Wang, Qiu-Ying
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p. 626 - 627
(2007/10/03)
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- Selenium-linking strategy for traceless solid-phase synthesis of acrylamides
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A novel polystyrene-supported β-selenopropionic acid has been developed and applied to simple and efficient synthesis of acrylamides.
- Sheng, Shou-Ri,Wang, Xing-Cong,Liu, Xiao-Ling,Song, Cai-Sheng
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p. 2867 - 2872
(2007/10/03)
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- A new route to N-aryl 2-alkenamides, N-allyl N-aryl 2-alkenamides, and N-aryl α,β-unsaturated γ-lactams from N-aryl 3-(phenylsulfonyl)propanamides
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A series of N-aryl 2-alkenamides were produced efficiently by treating N-aryl 3-(phenylsulfonyl)-propanamides with potassium tert-butoxide in THF at 0°C. Without isolation, it was further treated with an additional equivalent of potassium tert-butoxide and allyl bromide to give N-allyl N-aryl 2-alkenamides in one pot in good yields. Followed by a ring-closing metathesis reaction, these N-allyl N-aryl 2-alkenamides were respectively converted into corresponding N-aryl α,β-unsaturated γ-lactams in moderate yields.
- Wang, Eng-Chi,Huang, Keng-Shiang,Lin, Gwo-Woei,Lin, Jia-Ruei,Hsu, Ming-Kun
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- Synthesis of Benzoquinolizine Derivatives
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The reaction of α,β-unsaturated acids with aromatic amines in the presence of PPA affords directly benzo-quinolizines (I).The structures of all the compounds have been established on the basis of elemental analyses and spectral data.
- Merchant, J. R.,Pathare, P. M.
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p. 471 - 472
(2007/10/02)
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