- Molybdenum-Catalyzed Stannylations as Key Steps in Heterocyclic Synthesis
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THF/carbonyl complexes of molybdenum and tungsten are suitable precursors for the synthesis of the corresponding monoisonitrile carbonyl complexes. Whereas complexes with electron-rich isonitriles are suitable for regioselective hydrostannations, complexe
- Braune, Sascha,Pohlman, Matthias,Kazmaier, Uli
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- Small molecule microarray identifies inhibitors of tyrosyl-DNA phosphodiesterase 1 that simultaneously access the catalytic pocket and two substrate binding sites
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Tyrosyl-DNA phosphodiesterase 1 (TDP1) is a member of the phospholipase D family of enzymes, which catalyzes the removal of both 3′- and 5′-DNA phosphodiester adducts. Importantly, it is capable of reducing the anticancer effects of type I topoisomerase (TOP1) inhibitors by repairing the stalled covalent complexes of TOP1 with DNA. It achieves this by promoting the hydrolysis of the phosphodiester bond between the Y723 residue of human TOP1 and the 3′-phosphate of its DNA substrate. Blocking TDP1 function is an attractive means of enhancing the efficacy of TOP1 inhibitors and overcoming drug resistance. Previously, we reported the use of an X-ray crystallographic screen of more than 600 fragments to identify small molecule variations on phthalic acid and hydroxyquinoline motifs that bind within the TDP1 catalytic pocket. Yet, the majority of these compounds showed limited (millimolar) TDP1 inhibitory potencies. We now report examining a 21?000-member library of drug-like Small Molecules in Microarray (SMM) format for their ability to bind Alexa Fluor 647 (AF647)-labeled TDP1. The screen identified structurally similarN,2-diphenylimidazo[1,2-a]pyrazin-3-amines as TDP1 binders and catalytic inhibitors. We then explored the core heterocycle skeleton using one-pot Groebke-Blackburn-Bienayme multicomponent reactions and arrived at analogs having higher inhibitory potencies. Solving TDP1 co-crystal structures of a subset of compounds showed their binding at the TDP1 catalytic site, while mimicking substrate interactions. Although our original fragment screen differed significantly from the current microarray protocol, both methods identified ligand-protein interactions containing highly similar elements. Importantly inhibitors identified through the SMM approach show competitive inhibition against TDP1 and access the catalytic phosphate-binding pocket, while simultaneously providing extensions into both the substrate DNA and peptide-binding channels. As such, they represent a platform for further elaboration of trivalent ligands, that could serve as a new genre of potent TDP1 inhibitors.
- Zhao, Xue Zhi,Kiselev, Evgeny,Lountos, George T.,Wang, Wenjie,Tropea, Joseph E.,Needle, Danielle,Hilimire, Thomas A.,Schneekloth, John S.,Waugh, David S.,Pommier, Yves,Burke, Terrence R.
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p. 3876 - 3884
(2021/04/02)
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- Silver-Catalyzed Selective Multicomponent Coupling Reactions of Arynes with Nitriles and Isonitriles
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Pathway selective aryne-based novel multicomponent coupling reactions with isonitriles and nitriles are described. Crucial to these reactions is the formation of a silver-aryne complex, which shows differential reactivity toward isonitriles and nitriles to form two different forms of ortho-nitrilium organosilver arene species. Interception of the nitrilium of an aryne-isonitrile adduct with another isonitrile leads to the formation of benzocyclobutene-1,2-diimines, whereas the nitrilium of an aryne-nitrile adduct renders selective formation of 3H-indol-3-imines or 3-iminoindolin-2-ol depending on the structure of the nitrile employed.
- Ghorai, Sourav,Lin, Yongjia,Xia, Yuanzhi,Wink, Donald J.,Lee, Daesung
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p. 642 - 647
(2020/01/31)
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- Mild C?F Activation in Perfluorinated Arenes through Photosensitized Insertion of Isonitriles at 350 nm
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Fluorinated compounds have become important in the fields of agrochemical industry, pharmaceutical chemistry and materials sciences. Accordingly, various methods for their preparation have been developed in the past. Fluorinated compounds can be accessed via conjugation with fluorinated building blocks, via C?H fluorination or via selective activation of perfluorinated compounds to give the partially fluorinated congeners. Especially the direct activation of C?F bonds, one of the strongest σ-bonds, still remains challenging and new strategies for C?F activation are desirable. Herein a method for the photochemical activation of aromatic C?F bonds is presented. It is shown that isonitriles selectively insert into aromatic C?F bonds while aliphatic C?F bonds remain unaffected. Mechanistic studies reveal the reaction to proceed via the indirect excitation of the isonitrile to its triplet state by photoexcited acetophenone at 350 nm. Due to the relatively mild light used, the process shows high functional group tolerance and various compounds of the class of benzimidoyl fluorides are accessible from aryl isonitriles and commercially available perfluorinated arenes. (Figure presented.).
- Weidlich, Frauke,Esumi, Naoto,Chen, Dongyang,Mück-Lichtenfeld, Christian,Zysman-Colman, Eli,Studer, Armido
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p. 376 - 383
(2019/11/19)
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- Design, synthesis and biological evaluation of novel α-acyloxy carboxamides via Passerini reaction as caspase 3/7 activators
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Evasion of apoptosis is a hallmark of cancer. Caspases; the key executors of apoptotic cascade are attractive targets for selective induction of apoptosis in cancer cells. Within this approach, various caspase activators were introduced as lead anticancer agents. In the current study, a new series of multifunctional Passerini products was synthesized and evaluated as potent caspase-dependent apoptotic inducers. The synthetic strategy adopted this isocyanide-based multicomponent reaction to possibly mimic the pharmacophoric features of various lead apoptotic inducers, where a series of α-acyloxy carboxamides was prepared from p-nitrophenyl isonitrile, cyclohexanone and various carboxylic acids. Accordingly, the main amide-based scaffold was decorated by substituents with varying nature and size to gain more information about structure-activity relationship. All the synthesized compounds were screened for cytotoxicity against normal human fibroblasts and their potential anticancer activities against three human cancer cell lines; MCF-7 (breast), NFS-60 (myeloid leukemia), and HepG-2 (liver) utilizing MTT assay. Among the most active compounds, 13, 21 and 22 were more potent and safer than doxorubicin with nanomolar IC50 values and promising selectivity indices. Mechanistically, 13, 21 and 22 induced apoptosis by significant caspase activation in all the screened cancer cell lines utilizing flow cytometric analysis and caspase 3/7 activation assay. Again, 13 and 21 recorded higher activation percentages than doxorubicin, while 22 showed comparable results. Apoptosis-inducing factor1 (AIF1) quantification assay declared that 13, 21 and 22 didn't mediate apoptosis through AIF1-dependent pathway (i.e. only by caspase activation). Physicochemical properties, pharmacokinetic profiles, ligand efficiency metrics and drug-likeness data of all the synthesized compounds were computationally predicted and showed that 13, 21 and 22 could be considered as drug-like candidates. Finally, selected compounds were preliminarily screened for possible antimicrobial activities searching for dual anticancer/antimicrobial agents as an advantageous approach for cancer therapy.
- Salah Ayoup, Mohammed,Wahby, Yasmin,Abdel-Hamid, Hamida,Ramadan, El Sayed,Teleb, Mohamed,Abu-Serie, Marwa M.,Noby, Ahmed
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p. 340 - 356
(2019/03/04)
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- Palladium-Catalyzed Diarylation of Isocyanides with Tetraarylleads for the Selective Synthesis of Imines and α-Diimines
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Using tetraaryllead compounds (PbAr4) as arylating reagents, isocyanides undergo selective diarylation in the presence of palladium catalysts such as Pd(OAc)2 or Pd(PPh3)4 to afford imines and/or α-diimines based on the isocyanide employed. With aliphatic isocyanides, imines are obtained preferentially, whereas α-diimines are formed in the case of electron-rich aromatic isocyanides. The differences in imine/α-diimine selectivity can be attributed to the stability of imidoylpalladium intermediates formed in this catalytic reaction. Compared with other arylating reagents, tetraaryllead compounds are excellent candidates for use in the selective transformations to imines and/or α-diimines, especially in terms of inhibiting the oligomerization of isocyanides, which results in a lower product selectivity in many transition-metal-catalyzed reactions of isocyanides.
- Tran, Cong Chi,Kawaguchi, Shin-Ichi,Kobiki, Yohsuke,Matsubara, Hitomi,Tran, Dat Phuc,Kodama, Shintaro,Nomoto, Akihiro,Ogawa, Akiya
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p. 11741 - 11751
(2019/10/02)
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- Synthesis of Imides, Imidates, Amidines, and Amides by Intercepting the Aryne-Isocyanide Adduct with Weak Nucleophiles
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New aryne-based multicomponent coupling reactions for the formation of functionalized aromatic compounds have been developed. Arynes generated from triynes or tetraynes through the hexadehydro Diels-Alder reaction readily react with isocyanide to generate nitrilium intermediate. Intercepting this nitrilium species with various weak nucleophile including carboxylic acids, alcohols, sulfonamides, or water generated the corresponding imides, imidates, amidines, or amides. The high regioselectivity of these transformations was mainly controlled by the substituents of the arynes.
- Ghorai, Sourav,Lee, Daesung
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p. 7390 - 7393
(2019/10/02)
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- Selective Gold-Catalysed Synthesis of Cyanamides and 1-Substituted 1H-Tetrazol-5-Amines from Isocyanides
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The newly discovered gold-catalysed reaction of isocyanides with hydrazoic acid generated in situ from trimethylsilyl azide and methanol (or, alternatively, from NaN3/AcOH) produces either cyanamides or 1-substituted 1H-tetrazol-5-amines, depending on the amount of available HN3. The reaction proceeds selectively and in generally high yields of either product, thus providing a particularly convenient access to a wide range of substituted 1H-tetrazol-5-amines that are rather difficult to access otherwise.
- ?koch, Karel,Císa?ová, Ivana,?těpni?ka, Petr
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p. 13788 - 13791
(2018/09/14)
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- One-step synthesis of N, N′-substituted 4-imidazolidinones by an isocyanide-based pseudo-five-multicomponent reaction
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A pseudo-five-multicomponent reaction involving an isocyanide, a primary amine, two molecules of formaldehyde and water is reported, which gives N,N′-substituted 4-imidazolidinones when trifluoroethanol is used as the solvent. The reaction proceeds with good yields and with a wide variety of amines and isocyanides, providing an efficient new entry to these heterocycles. A preliminary study of the reaction mechanism suggests that trifluoroethanol, although acting as the solvent, is directly involved as a reagent in the reaction pathway.
- Attorresi, Cecilia I.,Bonifazi, Evelyn L.,Ramírez, Javier A.,Gola, Gabriel F.
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p. 8944 - 8949
(2018/12/10)
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- TEMPO-Catalyzed Aerobic Oxidative Selenium Insertion Reaction: Synthesis of 3-Selenylindole Derivatives by Multicomponent Reaction of Isocyanides, Selenium Powder, Amines, and Indoles under Transition-Metal-Free Conditions
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A novel and efficient approach for the selenium functionalization of indoles was developed with selenium powder as the selenium source, catalyzed by 2,2,6,6-tetramethylpiperidinooxy (TEMPO) and employing O2 as the green oxidant. This protocol provides a practical route for the synthesis of 3-selenylindole derivatives and has the advantages of readily available starting materials, mild reaction conditions, and a wide scope of substrates. Electron spin-resonance (ESR) studies reveal that the approach involves the formation of nitrogen-centered radicals and selenium radicals via oxidation of in situ generated selenoates.
- Liu, Huan,Fang, Yi,Wang, Shun-Yi,Ji, Shun-Jun
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supporting information
p. 930 - 933
(2018/02/22)
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- Development of an Industrial Process Based on the Groebke-Blackburn-Bienaymé Multicomponent Reaction: Efficient Preparation- of 3-Aminoimidazo[1,2-a]pyrazines
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3-Aminoimidazo[1,2-a]pyrazine is an important scaffold that is found in many drugs. This scaffold is rapidly accessible through a Groebke-Blackburn-Bienaymé cyclisation starting from an aminopyrazine, an aldehyde and an isocyanide. A scale-up process of this multicomponent reaction has been achieved in high yield and with excellent purity. The scope and limitations of this process leading to various 3-aminoimidazo[1,2-a]pyrazines are disclosed.
- Baenziger, Markus,Durantie, Estelle,Mathes, Christian
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p. 2266 - 2274
(2017/05/05)
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- Aerobic radical-cascade cycloaddition of isocyanides, selenium and imidamides: Facile access to 1,2,4-selenadiazoles under metal-free conditions
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A novel and facile metal-free method for the green synthesis of 1,2,4-selenadiazol-5-amine derivatives through the aerobic radical-cascade multi-component reactions of isocyanides, selenium powder and imidamides is reported herein. O2 in the air was employed as the green oxidant to achieve the cycloaddition with the generation of H2O as the sole by-product. It also features good functional group compatibility and broad substrate scope. In addition, this method was successfully applied to the functionalization of biologically active molecules.
- Fang, Yi,Zhu, Zheng-Lin,Xu, Pei,Wang, Shun-Yi,Ji, Shun-Jun
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supporting information
p. 1613 - 1618
(2017/06/05)
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- Cobalt(II)-Catalyzed Isocyanide Insertion Reaction with Sulfonyl Azides in Alcohols: Synthesis of Sulfonyl Isoureas
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A Co(II)-catalyzed isocyanide insertion reaction with sulfonyl azides in alcohols to form sulfonyl isoureas via nitrene intermediate has been developed. This protocol provides a new, environmentally friendly, and simple strategy for the synthesis of sulfonyl isourea derivatives by employing a range of substrates under mild conditions.
- Jiang, Tian,Gu, Zheng-Yang,Yin, Ling,Wang, Shun-Yi,Ji, Shun-Jun
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supporting information
p. 7913 - 7919
(2017/08/14)
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- Synthesis and structure–activity relationship of α-keto amides as enterovirus 71 3C protease inhibitors
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α-Keto amide derivatives as enterovirus 71 (EV71) 3C protease (3Cpro) inhibitors have been synthesized and assayed for their biochemical and antiviral activities. structure–activity relationship (SAR) study indicated that small moieties were primarily tolerated at P1' and the introduction of para-fluoro benzyl at P2 notably improved the potency of inhibitor. Inhibitors 8v, 8w and 8x exhibited satisfactory activity (IC50= 1.32 ± 0.26 μM, 1.88 ± 0.35 μM and 1.52 ± 0.31 μM, respectively) and favorable CC50values (CC50> 100 μM). α-Keto amide may represent a good choice as a warhead for EV71 3Cproinhibitor.
- Zeng, Debin,Ma, Yuying,Zhang, Rui,Nie, Quandeng,Cui, Zhengjie,Wang, Yaxin,Shang, Luqing,Yin, Zheng
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supporting information
p. 1762 - 1766
(2016/12/22)
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- From isonitriles to unsaturated NHC complexes of gold, palladium and platinum
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In a modular template synthesis, unsaturated NHC complexes of gold, palladium and platinum were synthesized from simple metal salts, isonitriles and amines with acetal or ketal groups. Upon the addition of amines with tethered acetal or ketal moieties to the metal-activated isonitrile, first nitrogen acyclic carbene (NAC) complexes are formed. These undergo ring closure and elimination to the unsaturated NHC complexes upon addition of acid. This simple strategy opens an attractive and fast approach to NHC complexes of gold, palladium and platinum. The modular approach allows a fast modification and is well-suited for the synthesis of unsymetrically and symmetrically substituted unsaturated NHC complexes.
- Riedel, Dominic,Wurm, Thomas,Graf, Katharina,Rudolph, Matthias,Rominger, Frank,Hashmi, A. Stephen K.
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p. 1515 - 1523
(2015/05/19)
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- Synthesis of isonitriles from N-substituted formamides using triphenylphosphine and iodine
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Treatment of N-substituted formamides with the reagent combination of triphenylphosphine and molecular iodine, in the presence of a tertiary amine, quickly produces the corresponding isocyanides in high yields under ambient conditions. The process employs readily available and low-cost reagents, a convenient synthetic procedure, and mild reaction conditions for the synthesis of various alkyl and aryl isocyanides.
- Wang, Xia,Wang, Qing-Gang,Luo, Qun-Li
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- Palladium-Catalyzed Synthesis of α-Diimines from Triarylbismuthines and Isocyanides
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In this study, we report a highly selective coupling reaction between triarylbismuthines and isocyanides using palladium diacetate as the catalyst, affording α-diimines, with the formation of three C-C bonds. Among several aryl sources (Ar-YLn: Y = B, Sn, Pb, Sb, Bi, I), only triarylbismuthines successfully undergo coupling with isocyanides to selectively afford α-diimines. The coupling reaction exhibits the advantages of high atom economy and convenient operation, with no need for any additive.
- Kobiki, Yohsuke,Kawaguchi, Shin-Ichi,Ogawa, Akiya
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supporting information
p. 3490 - 3493
(2015/07/28)
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- Synthesis of isocyanides through dehydration of formamides using XtalFluor-E
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The formation of isocyanides from formamides using XtalFluor-E, [Et2NSF2]BF4, is presented. A wide range of formamides can be used to produce the corresponding isocyanides in up to 99% yield. In a number of cases, the crude products showed good purity (generally >80% by NMR) allowing to be used directly in multi-component reactions.
- Keita, Massaba,Vandamme, Mathilde,Mahé, Olivier,Paquin, Jean-Fran?ois
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supporting information
p. 461 - 464
(2015/03/05)
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- Novel ultrasound-promoted parallel synthesis of trifluoroatrolactamide library via a one-pot passerini/hydrolysis reaction sequence and their fungicidal activities
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An ultrasound-promoted one-pot Passerini/hydrolysis reaction sequence has been developed for the synthesis of trifluoroatrolactamide derivatives using a diverse range of trifluoroacetophenones and isonitriles in acetic acid. Parallel synthesis in a centrifuge tube using a noncontact ultrasonic cell crusher was used in this study as an efficient method for the rapid generation of combinatorial trifluoroatrolactamide libraries, and subsequent biochemical evaluation of the resulting compounds indicated that they possessed excellent broad-spectrum fungicidal activities. N-(4-chlorophenyl)-2-(4-ethylphenyl)-3,3, 3-trifluoro-2-hydroxypropanamide and N-(4-chlorophenyl)-3,3,3-trifluoro-2- hydroxy-2-(4-methoxyphenyl)propanamide, in particular, showed significant fungicidal activities against all of the fungal species tested in the current study.
- Yu, Shu-Jing,Zhu, Cong,Bian, Qiang,Cui, Can,Du, Xiu-Jiang,Li, Zheng-Ming,Zhao, Wei-Guang
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supporting information
p. 17 - 23
(2014/02/14)
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- A general simple methodology for synthesis of isonitriles using benzene-1,3-disulfonyl dichloride
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Isonitrile derivatives have been synthesized in good to high yields by dehydration of aliphatic and aromatic formamides in the presence of benzene-1,3-disulfonyl dichloride as easy and efficient reagent.
- Ghorbani-Vaghei, Ramin,Amiri, Mostafa,Veisi, Hojat
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- Efficient one-pot synthesis of unsymmetrical gold(I) N-heterocyclic carbene complexes and their use as catalysts
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Eleven different gold(I) complexes of new NHC ligands were prepared in excellent yield, demonstrating the versatility of the new route to NHC complexes. While the influence of electronically different ligands on the synthesis of the catalysts was small, the catalytic activities of the products differed significantly.
- Hashmi, A. Stephen K.,Yu, Yang,Rominger, Frank
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p. 895 - 904
(2012/04/04)
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- On the reaction of carboxylic acids and isonitriles with conventional heating
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Control over the formation of N-formylamides versus the formation of captodative alkenes from the reaction of arylacetic acids with isonitriles has been achieved. Low temperatures and high concentrations favor alkenes, and high temperatures and low concen
- Polisar, Jason G.,Norton, Jack R.
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supporting information
p. 10236 - 10240,5
(2020/09/02)
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- A novel method for preparing isocyanides from N-substituted formamides with chlorophosphate compounds
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Treatment of N-substituted formamides with chlorophosphate compounds such as PhOPOCl2, EtOPOCl2, Me2NPOCl2, and (PhO)2POCl and tertiary amines such as triethylamine, pyridine, and N,N-diisopropylethylamine produced the corresponding isocyanides in high yields. This method can be used to prepare various alkyl and aryl isocyanides. Georg Thieme Verlag Stuttgart · New York.
- Kobayashi, Genki,Saito, Tateo,Kitano, Yoshikazu
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p. 3225 - 3234
(2011/11/30)
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- Oxidation of arylthiourea by cetyltrimethylammonium dichromate
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With a view to investigate the oxidation behaviors of cetyltrimethylammonium dichromate on multifunctional groups, some arylthioureas were subjected to oxidation, both in neutral and in acidic conditions. In neutral conditions, the products were found to be a mixture of corresponding urea and isonitrile. In acidic conditions, the products were corresponding ureas only. A probable mechanism was proposed for the formation of the product, wherein the first step involves coupling of-NH2 and-SH of one molecule to the-NH2 and-SH of another molecule, respectively, which is followed by removal of nitrogen and sulfur. The microwave irradiation resulted in great yield of isonitrile than urea in neutral conditions. Supplemental materials are available for this article. Go to the publisher's online edition of Synthetic Communications to view the free supplemental file. Copyright Taylor & Francis Group, LLC.
- Sahu, Sandhyamayee,Sahoo, Prangya Rani,Patel, Sabita,Mishra
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experimental part
p. 3268 - 3273
(2010/12/24)
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- CHEMICAL COMPOUNDS
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This invention relates to non-steroidal compounds that are modulators of androgen receptor, and also to the methods for the making and use of such compounds.
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- Microwave-assisted synthesis of isonitriles: A general simple methodology
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(Chemical Equation Presented) A facile conversion of formamides to isonitriles under very mild conditions and microwave irradiation is described. This simple and efficient method has been applied for the synthesis of both aliphatic and aromatic isonitriles in high yields.
- Porcheddu, Andrea,Giacomelli, Giampaolo,Salaris, Margherita
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p. 2361 - 2363
(2007/10/03)
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- p-Nitrophenyl isocyanide
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Achiral p-nitrophenyl isocyanide, C7H4N 2O2, crystallizes in the orthorhombic chiral space group P212121. Attractive intermolecular interactions between the nitro O atoms and both aromatic H and nitro N atoms of neighbouring molecules are observed. The O...N interaction is surprisingly strong [N...O = 2.869 (2) A] compared with other aromatic nitro compounds.
- Zeller, Matthias,Hunter, Allen D.
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p. o415-o417
(2007/10/03)
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- Novel hexakis(areneisonitrile)technetium(I) complexes as radioligands targeted to the multidrug resistance P-glycoprotein
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Transport substrates and modulators of the human multidrug resistance (MDR1) P-glycoprotein (Pgp) are generally lipophilic cationic compounds, many with substituted aryl moieties. We sought to synthesize aromatic technetium isonitrile complexes to enable
- Herman,Sharma,Kronauge,Barbarics,Herman,Piwnica- Worms
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p. 2955 - 2963
(2007/10/02)
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- THE INVENTION OF RADICAL REACTIONS PART XVIII. A CONVENIENT SOLUTION TO THE 1-CARBON PROBLEM (R-CO2H --> R-13CO2H)
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Radicals generated by photolysis (W light) of esters derived from N-hydroxy-2-thiopyridone react with electrophilic isocyanides 2a and (in the presence of trifluoroacetic acid) 2b to give adducts of type 3.Convenient reaction procedures have been worked out to hydrolyse the adducts to amides of type 5, from which the original acid can be regenerated under mild conditions.The three important acids oleic, linoleic and arachidonic have all given smooth reactions.In suitable examples, quantitative evolution of carbon dioxide and incorporation of 13C without dilution have been demonstrated.This reaction sequence will be useful for the labelling in the carboxyl group of prostaglandins, leukotrienes, and the side chain carboxyls of peptides.
- Barton, Derek H. R.,Ozbalik, Nubar,Vacher, Bernard
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p. 3501 - 3512
(2007/10/02)
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- Formimidoyl Group Transfer from Activated Amidines. Part 1. Hydrolysis of 1-(N-t-Butylformimidoyl)imidazole and Related Imidazole-containing Formamides
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The hydrolysis of 1-(N-t-butylformimidoyl)imidazole (7a) to t-butylformamide and imidazole has been examined in the absence of buffer species at 25 deg C in water.The rate of hydrolysis was pH-independent at pH 7-14 and reaction in this region is shown to occur via HO- attack on the protonated substrate (whose pKa is 5.0; protonation site, imidazole nitrogen).Alternative mechanisms such as H2O attack on the neutral substrate and reaction via the zwitterion (15) were eliminated using solvent isotope effect, deuterium labelling, and substituent effects.Below pH 6 acid catalysis of hydrolysis is observed due to H2O reaction with the protonated substrate (pH 4-6) and with the diprotonated substrate (pH 0-4); at pH 0, t1/2 for hydrolysis is -2s.The N-arylformamidines (7b) and (7c) react via similar acid catalysed pathways but a new reaction (identified as HO- attack on the amidine) occurs in base, in preference to the pH independent pathways. p-Nitrophenylformamide is itself hydrolysed in basic solution so that complex kinetics result.The C-substitued amidines (7e) and (7f) react 104-102-fold more slowly than the corresponding formamidines.Buffer catalysis of the hydrolysis of (7a) by phosphate and amines is complex, the slope of kobs. versus plots being greater at low than at high buffer concentrations.This is consistent with the formation of a tetrahedral intermediate in the reaction pathway whose formation and beakdown is subject to general acid-base catalysis.
- Chandler, Anne,Hegarty, Anthony F.,McCormack, Margaret T.
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p. 1318 - 1325
(2007/10/02)
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