- Site-Selective, Remote sp3 C?H Carboxylation Enabled by the Merger of Photoredox and Nickel Catalysis
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A photoinduced carboxylation of alkyl halides with CO2 at remote sp3 C?H sites enabled by the merger of photoredox and Ni catalysis is described. This protocol features a predictable reactivity and site selectivity that can be modulated by the ligand backbone. Preliminary studies reinforce a rationale based on a dynamic displacement of the catalyst throughout the alkyl side chain.
- Sahoo, Basudev,Bellotti, Peter,Juliá-Hernández, Francisco,Meng, Qing-Yuan,Crespi, Stefano,K?nig, Burkhard,Martin, Ruben
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supporting information
p. 9001 - 9005
(2019/06/24)
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- BORON-BASED CYCLOADDITION CATALYSTS AND METHODS FOR THE PRODUCTION OF BIO-BASED TEREPHTHALIC ACID, ISOPHTHALIC ACID AND POLY (ETHYLENE TEREPHTHALATE)
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Methods for producing cycloaddition products comprising: reacting a diene with a dienophile in the presence of one or more boron-based catalysts of Formula I or Formula II are provided. In particular, the methods can be used to prepare 4-methyl-3-cyclohexene- 1-carboxylic acid and 3-methyl-3-cyclohexene-l-carboxylic acid, including bio-based versions thereof. The cycloaddition products can be advantageously used in the production of terephthalic acid and isophthalic acid, and ultimately, poly(ethylene terephthalate), and bio-based versions thereof. Formula I Formula II
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Paragraph 00224-00227
(2017/04/11)
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- Radical-Mediated Dearomatization of Indoles with Sulfinate Reagents for the Synthesis of Fluorinated Spirocyclic Indolines
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The dearomative introduction of trifluoromethyl and 1,1-difluoroethyl radicals, generated from their corresponding sulfinate salts, into the C2 position of indole derivatives allows the diastereoselective synthesis of three-dimensional 3,3-spirocyclic indolines over C-H functionalized indoles.
- Ryzhakov, Dmytro,Jarret, Maxime,Guillot, Régis,Kouklovsky, Cyrille,Vincent, Guillaume
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supporting information
p. 6336 - 6339
(2017/12/08)
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- Sodium Iodide/Hydrogen Peroxide-Mediated Oxidation/Lactonization for the Construction of Spirocyclic Oxindole-Lactones
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The sodium iodide/hydrogen peroxide-mediated oxidation/lactonization of indolepropionic acids was achieved, affording the corresponding spirocyclic oxindole-lactones in moderate to high yields. This metal-free procedure features mild reaction conditions, non-toxicity and easy handling, with hydrogen peroxide (H2O2) as a clean oxidant. (Figure presented.).
- Li, Guofeng,Huang, Liwu,Xu, Jiecheng,Sun, Wangsheng,Xie, Junqiu,Hong, Liang,Wang, Rui
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supporting information
p. 2873 - 2877
(2016/09/16)
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- SUBSTITUTED INDOLE MCL-1 INHIBITORS
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The present invention provides for compounds that inhibit the activity of an anti-apoptotic Bcl-2 family member Myeloid cell leukemia-1 (Mcl-1) protein. The present invention also provides for pharmaceutical compositions as well as methods for using compounds for treatment of diseases and conditions (e.g., cancer) characterized by the over-expression or dysregulation of Mcl-1 protein.
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Paragraph 00402
(2015/12/08)
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- Two-photon sensitive protecting groups operating via intramolecular electron transfer: Uncaging of GABA and tryptophan
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Improved photo-labile protecting groups, with high sensitivity to two-photon excitation, are needed for the controlled release of drugs, as tools in neuroscience and physiology. Here we present a new modular approach to the design of caging groups based on photoinduced electron transfer from an electron-rich two-photon dye to an electron acceptor, followed by scission of an ester to release a carboxylic acid. Three different electron acceptors were tested: nitrobenzyl, phenacyl and pyridinium. The nitrobenzyl system was ineffective, giving only photochemical decomposition and no release of the carboxylic acid. The phenacyl system also performed poorly, liberating the carboxylic acid in 20% chemical yield and 0.2% photochemical yield. The pyridinium system was most successful, and was tested for the release of two carboxylic acids: γ-amino butyric acid (GABA) and tryptophan. The caged GABA undergoes photochemical cleavage with a chemical yield of >95% and a photochemical yield of 1%; it exhibits a two-photon absorption cross section of 1100 GM at 700 nm, corresponding to a two-photon uncaging cross section of 10 ± 3 GM. This journal is
- Korzycka, Karolina A.,Bennett, Philip M.,Cueto-Diaz, Eduardo Jose,Wicks, Geoffrey,Drobizhev, Mikhail,Blanchard-Desce, Mireille,Rebane, Aleksander,Anderson, Harry L.
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p. 2419 - 2426
(2015/03/30)
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- Kinetic mechanism of human histidine triad nucleotide binding protein 1
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Human histidine triad nucleotide binding protein 1 (hHint1) is a member of a ubiquitous and ancient branch of the histidine triad protein superfamily. hHint1 is a homodimeric protein that catalyzes the hydrolysis of model substrates, phosphoramidate and acyl adenylate, with a high efficiency. Recently, catalytically inactive hHint1 has been identified as the cause of inherited peripheral neuropathy [Zimon, M., et al. (2012) Nat. Genet. 44, 1080-1083]. We have conducted the first detailed kinetic mechanistic studies of hHint1 and have found that the reaction mechanism is consistent with a double-displacement mechanism, in which the active site nucleophile His112 is first adenylylated by the substrate, followed by hydrolysis of the AMP-enzyme intermediate. A transient burst phase followed by a linear phase from the stopped-flow fluorescence assay indicated that enzyme adenylylation was faster than the subsequent intermediate hydrolysis and product release. Solvent viscosity experiments suggested that both chemical transformation and diffusion-sensitive events (product release or protein conformational change) limit the overall turnover. The catalytic trapping experiments and data simulation indicated that the true koff rate of the final product AMP is unlikely to control the overall kcat. Therefore, a protein conformational change associated with product release is likely rate-limiting. In addition, the rate of Hint1 adenylylation was found to be dependent on two residues with pKa values of 6.5 and 8, with the former pKa agreeing well with the nuclear magnetic resonance titration results for the pKa of the active site nucleophile His112. In comparison to the uncatalyzed rates, hHint1 was shown to enhance acyl-AMP and AMP phosphoramidate hydrolysis by 106-108-fold. Taken together, our analysis indicates that hHint1 catalyzes the hydrolysis of phosphoramidate and acyl adenylate with high efficiency, through a mechanism that relies on rapid adenylylation of the active residue, His112, while being partially rate-limited by intermediate hydrolysis and product release associated with a conformational change. Given the high degree of sequence homology of Hint proteins across all kingdoms of life, it is likely that their kinetic and catalytic mechanisms will be similar to those elucidated for hHint1.
- Zhou, Xin,Chou, Tsui-Fen,Aubol, Brandon E.,Park, Chin Ju,Wolfenden, Richard,Adams, Joseph,Wagner, Carston R.
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p. 3588 - 3600
(2013/07/28)
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- A systematic study of two complementary protocols allowing the general, mild and efficient deprotection of N-pivaloylindoles
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Two mild and general protocols for the high-yielding deprotection of indoles and related fused heterocyclic systems are described, involving either hydride transfer from LDA or hydrolysis by the DBU-water system. Both methods were shown to tolerate a wide variety of substituents and functional groups, but the hydrolytic one proved to be particularly general, being compatible with 2-alkyl substituents, aldehydes, ketones, carboxylic acids, halogens, ethers, amides and esters. Yields were normally excellent in both cases, but were usually slightly higher for the reductive method. Taken together, these two protocols provide a general solution to the problem of pivaloyindole deprotection.
- Ruiz, Míriam,Sánchez, J. Domingo,López-Alvarado, Pilar,Menéndez, J. Carlos
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experimental part
p. 705 - 710
(2012/01/06)
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- Enantioselective copper-catalyzed construction of aryl pyrroloindolines via an arylation-cyclization cascade
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An enantioselective arylation-cyclization cascade has been accomplished using a combination of diaryliodonium salts and asymmetric copper catalysis. These mild catalytic conditions provide a new strategy for the enantioselective construction of pyrroloindolines, an important alkaloid structural motif that is commonly found among biologically active natural products.
- Zhu, Shaolin,MacMillan, David W. C.
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supporting information; experimental part
p. 10815 - 10818
(2012/08/07)
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- 3-(3-INDOLYL) PROPIONIC ACID CALCIUM SALT AND METHOD OF MAKING 3-(3-INDOLYL) PROPIONIC ACID FREE ACID THEREFROM
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Substantially pure 3-(3-indolyl)propionic acid free acid is synthesized by converting the free acid to 3-(3-indolyl)propionic acid calcium salt (3-IPA calcium), precipitating and washing, and then reconverting the 3-IPA calcium to the free acid. 3-IPA calcium is suitable for use in pharmaceutical compositions in tablet and sustained-release dosage forms. 3-IPA calcium can be used to inhibit the cytotoxic effects of amyloid beta protein on cells, to treat fibrillogenic diseases in a mammal, and to treat diseases or conditions in which free radicals or oxidative stress plays a role.
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Page/Page column 17-18
(2008/06/13)
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- An efficient procedure for the deprotection of N-pivaloylindoles, carbazoles and β-carbolines with LDA
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Treatment of variously substituted indoles with 2 equivalents of LDA at 40-45 °C led to their fast and efficient deprotection. This method was also extended to N-pivaloylcarbazoles and β-carbolines.
- Avenda?o, Carmen,Sánchez, J. Domingo,Menéndez, J. Carlos
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p. 107 - 110
(2007/10/03)
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- PPAR ACTIVE COMPOUNDS
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Compounds are described that are active on PPARs, including pan-active compounds. Also described are methods for developing or identifying compounds having a desired selectivity profile.
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- PPAR active compounds
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Compounds are described that are active on PPARs, including pan-active compounds. Also described are methods for developing or identifying compounds having a desired selectivity profile.
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- 2-Aryl indole NK1 receptor antagonists: Optimisation of indole substitution
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The synthesis and biological evaluation of a series of 2-aryl indoles with high affinity for the human neurokinin-1 (hNK1) receptor are reported, concentrating on optimisation of the indole substitution.
- Cooper, Laura C.,Chicchi, Gary G.,Dinnell, Kevin,Elliott, Jason M.,Hollingworth, Gregory J.,Kurtz, Marc M.,Locker, Karen L.,Morrison, Denise,Shaw, Duncan E.,Tsao, Kwei-Lan,Watt, Alan P.,Williams, Angela R.,Swain, Christopher J.
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p. 1233 - 1236
(2007/10/03)
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- Solvolyses of 2-Deoxy-α- and β-D-Glucopyranosyl 4′-Bromoisoquinolinium Tetrafluoroborates
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The solvolyses of 2-deoxy-α- and β-D-glucopyranosyl 4′-bromoisoquinolinium tetrafluoroborates (1 and 2) were monitored in aqueous methanol, ethanol, trifluoroethanol, and binary mixtures of ethanol and trifluoroethanol. The observed rate constants are consistent with the solvolyses of 1 and 2 proceeding via dissociative (DN * AN) transition states. In comparison to the α-anomer, solvolysis of the β-compound gives a greater transition state charge delocalization onto the ring oxygen atom. Analysis of the solvolysis product ratios indicates that the 2-deoxyglucosyl oxacarbenium ion is not solvent-equilibrated in the solvent mixtures studied. In the solvolysis of compound 1, the solvent trifluoroethanol facilitates diffusional separation of the leaving group and, in so doing, promotes the formation of the retained trifluoroethyl glycoside.
- Zhu, Jiang,Bennet, Andrew J.
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p. 4423 - 4430
(2007/10/03)
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- Tyrosine kinase inhibitors. 1. Structure-activity relationships for inhibition of epidermal growth factor receptor tyrosine kinase activity by 2,3-dihydro-2-thioxo-1H-indole-3-alkanoic acids and 2,2'-dithiobis(1H- indole-3-alkanoic acids)
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A series of 2,3-dihydro-2-thioxo-1H-indole-3-alkanoic acids, and their methyl esters were prepared, the majority by oxidation of 1H-indole-3- alkanoic acids (DMSO/HCl), followed by thiation of the corresponding 2,3- dihydro-2-oxo-1H-indole-3-alkanoic acid esters. The monomeric thiones undergo facile and reversible oxidation to the corresponding 2,2'-dithiobis(1H- indole-3-alkanoic acids). The compounds were evaluated for their abilities to inhibit the tyrosine kinase activity of the epidermal growth factor receptor using a native complex contained in plasma membrane vesicles shed from cultured A431 cells, and to inhibit the growth of Swiss 3T3 mouse fibroblast in culture. Enzyme inhibitory activity is dependent on the length of the side chain, with propanoic acid derivatives showing the highest activity. The acids are generally significantly more potent than the corresponding esters, and the disulfides more active than the corresponding monomers. An ability to undergo the thione-thiol tautomerism necessary for dimerization is essential, with 3,3-disubstituted compounds being inactive. Overall, the data suggest that the disulfide is the more active form, with much of the activity of the monomeric thiones being due to varying degrees of conversion to the disulfide during the assay. In the growth inhibition assay, the methyl esters are more potent than their corresponding carboxylic acids, and the dimers are generally more potent than the monomers. The data show these compounds to be a novel and potent class of inhibitors of epidermal growth factor receptor tyrosine kinase activity.
- Thompson,Rewcastle,Tercel,Dobrusin,Fry,Kraker,Denny
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p. 2459 - 2469
(2007/10/02)
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- Indobine - a New Alkaloid from Rauwolfia serpentina Benth
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A new alkaloid indobine has been isolated from the roots of Rauwolfia serpentina obtained from Thailand and its structure was determined as benzylester of indole propionic acid through chemical and spectroscopic studies. - Key words: Indobine, Rauwolfia serpentina
- Siddiqui, Salimuzzaman,Haider, S. Imtiaz,Ahmad, S. Salman
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p. 783 - 784
(2007/10/02)
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- Isolation of Indobinine, a New Alkaloid from Roots of Rauwolfia serpentina Benth
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The alcoholic extract of the roots of Rauwolfia serpentina Benth yields a new alkaloid, indobinine.Its structure (I) has been elucidated as cyclohexyl ester of indolepropionic acid by spectral and chemical studies.
- Siddiqui, Salimuzzaman,Ahmad, S. Salman,Haider, S. Imtiaz
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p. 279 - 280
(2007/10/02)
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- Syntheses a partir de la cyano-2 cyclopentanone: application des arylhydrazones de l'acide cyano-5 oxo-5 pentanoique a la preparation de derives indoliques
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Fischer's cyclisation of 5-cyano 5-oxo pentanoic acid arylhydrazones affords either 3-(2-carboxy 1H-3-indolyl) propanoic acids and derivatives thereof, azepinoindoles or an acetyl diazepinone according to the nature of the cyclising reagent.
- Trinh, Thi Anh Nga,Lamant, Maurice
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p. 361 - 364
(2007/10/02)
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