- COMPOUNDS AND USES THEREOF IN THE TREATMENT OF CANCERS AND OTHER MEDICAL CONDITIONS
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There are provided compounds, their preparation and their use in the treatment of medical conditions including cancers and immune disorders.
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Paragraph 0101; 0103; 0114; 00128
(2017/02/09)
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- Highly efficient asymmetric hydrogenation of cyano-substituted acrylate esters for synthesis of chiral γ-lactams and amino acids
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A highly efficient and enantioselective synthesis of γ-lactams and γ-amino acids by Rh-catalyzed asymmetric hydrogenation has been developed. Using the Rh-(S,S)-f-spiroPhos complex, under mild conditions a wide range of 3-cyano acrylate esters including both E and Z-isomers and β-cyano-α-aryl-α,β-unsaturated ketones were first hydrogenated with excellent enantioselectivities (up to 98% ee) and high turnover numbers (TON up to 10 000).
- Kong, Duanyang,Li, Meina,Wang, Rui,Zi, Guofu,Hou, Guohua
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supporting information
p. 1216 - 1220
(2016/02/03)
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- (±)Methanodibenzodiazocine tethered [C-H]δ+ functional site: Study towards benzoin condensation and Baylis-Hillman reactions
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Abstract New heterocyclic ring systems consisting of (±) methanodibenzodiazocine and imidazolium/ benzimidazolium salts were synthesized in very good yield. Subsequently, these halide salts were subjected to the anion exchange reaction with KPF6 to yield the corresponding azolium salts in excellent yield. The possible applications of these newly prepared salts were investigated in homogeneous catalysis. Remarkable changes in the catalytic activity were observed by varying the bulkiness of N-substituent at imidazole. Catalytic activity of these newly prepared salts was tested for the benzoin condensation reaction. Exclusive formation of benzoin products were observed in good yield. Similarly, the dimerization of cyclohexen-1-one to Baylis-Hillman type product, 2-(3-oxocyclohexyl)-2-cyclohexen-1-one was studied. [Figure not available: see fulltext.]
- Sathyanarayana, Arruri,Prabusankar, Ganesan
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p. 821 - 831
(2015/08/06)
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- Rate and equilibrium constants for the addition of N-heterocyclic carbenes into benzaldehydes: A remarkable 2-substituent effect
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Abstract Rate and equilibrium constants for the reaction between N-aryl triazolium N-heterocyclic carbene (NHC) precatalysts and substituted benzaldehyde derivatives to form 3-(hydroxybenzyl)azolium adducts under both catalytic and stoichiometric conditions have been measured. Kinetic analysis and reaction profile fitting of both the forward and reverse reactions, plus onwards reaction to the Breslow intermediate, demonstrate the remarkable effect of the benzaldehyde 2-substituent in these reactions and provide insight into the chemoselectivity of cross-benzoin reactions. It takes 2-: Measurement of rate and equilibrium constants for the reaction between N-aryl triazolium NHC precatalysts and substituted benzaldehydes under catalytic and stoichiometric conditions demonstrate the remarkable kinetic and thermodynamic effect of the benzaldehyde 2-substituent in these reactions, potentially providing insight into the chemoselectivity of cross-benzoin reactions.
- Collett, Christopher J.,Massey, Richard S.,Taylor, James E.,Maguire, Oliver R.,O'Donoghue, AnnMarie C.,Smith, Andrew D.
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supporting information
p. 6887 - 6892
(2015/06/02)
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- Synthesis of new chiral keto alcohols by baker's yeast
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Fourteen chiral α- and β-keto alcohols 2a-2r were synthesized by the asymmetric reduction of their corresponding diketones 1a-1r via baker's yeast. In addition, ten corresponding racemic α-keto alcohols were synthesized by the benzoin condensation of their corresponding aldehydes, which were used for the determination of the ee values through their chiral resolution on chiral HPLC. Amongst the 15 diketones, 1j and chiral α-keto alcohols 2i, 2j and chiral β-keto alcohol 2r are novel compounds. Six keto alcohols 2b, 2c, 2d, 2f, 2h and 2p were synthesized by baker's yeast for the first time. There are some studies in the literature where baker's yeast was applied to the diketones 1a, 1g, 1e, 1k and 1n under various conditions different to those reported herein. The yields and the ee values of these studies were not as high as ours. All of the keto alcohols synthesized were characterized by IR, NMR (1H and 13C), and MS. The relationship between the structure of the diketone and the yield, diastereoselectivity and enantiomeric excess is also discussed.
- Yildiz, Tuelay,Canta, Nurguel,Yusufoglu, Ayse
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p. 340 - 347
(2014/04/03)
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- Enantioselective aerobic oxidation of α-hydroxy-ketones catalyzed by oxidovanadium(V) methoxides bearing chiral, N-salicylidene- tert -butylglycinates
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Chiral oxidovanadium(V) methoxides prepared from 3,5-disubstituted-N- salicylidene-l-tert-butylglycines and vanadyl sulfate in air-saturated MeOH serve as highly enantioselective catalysts for asymmetric aerobic oxidations and kinetic resolution of alkyl, aryl, and heteroaryl α-hydroxy-ketones with differed α-substituents at ambient temperature in toluene or TBME (tert-butyl methyl ether). The best scenarios involve the use of complexes which bear the tridendate templates derived from 3,5-diphenyl- or 3-o-biphenyl-5-nitro-salicyaldehyde. The kinetic resolution selectivities of the aerobic oxidation process are in the range of 12 to >1000 based on the selectivity factors (krel).
- Chen, Chien-Tien,Kao, Jun-Qi,Salunke, Santosh B.,Lin, Ya-Hui
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supporting information; experimental part
p. 26 - 29
(2011/03/22)
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- NHC gold halide complexes derived from 4,5-diarylimidazoles: Synthesis, structural analysis, and pharmacological investigations as potential antitumor agents
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A series of novel neutral NHC gold halide complexes derived from 4,5-diarylimidazoles were synthesized, characterized, and analyzed for biological effects. High growth inhibitory effects in MCF-7 and MDA-MB 231 breast cancer as well as HT-29 colon cancer cell lines depended on the presence of the C4,C5-standing aromatic rings. Methoxy groups at these rings did not change the growth inhibitory properties, while F-substituents in the ortho-position (5d) increased the activity in MCF-7 and MDA-MB 231 cells. The substituents at the nitrogen atoms and the oxidation state of the metal play a subordinate role. The most active bromo[1,3-diethyl-4,5-bis(2-fluorophenyl)-1,3- dihydro-2H-imidazol-2-ylidene]gold(I) (5d) was distinctly more active than cisplatin. All complexes caused thioredoxin reductase (TrxR) inhibition (EC 50 = 374-1505 nM) distinctly lower than auranofin (EC50 = 18.6 nM) excluding this enzyme as main target. Because of the low nuclear content, a participation of DNA interaction on the mode of action is very unlikely. The missing ER binding and the missing correlation of growth inhibition and inactivation of COX enzymes exclude these targets, too. (Figure presented)
- Liu, Wukun,Bensdorf, Kerstin,Proetto, Maria,Abram, Ulrich,Hagenbach, Adelheid,Gust, Ronald
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supporting information; experimental part
p. 8605 - 8615
(2012/02/03)
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- Exerting control over the acyloin reaction
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A synthetic method for conducting the acyloin reaction using electron transfer in solution is reported. By linking two esters via their oxygen atoms, it was possible to perform crossed acyloin reactions between two different ester functionalities and display a high degree of preference for an intramolecular coupling process.
- Donohoe, Timothy J.,Jahanshahi, Ali,Tucker, Michael J.,Bhatti, Farrah L.,Roslan, Ishmael A.,Kabeshov, Mikhail,Wrigley, Gail
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supporting information; experimental part
p. 5849 - 5851
(2011/06/27)
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- Highly chemoselective direct crossed aliphatic-aromatic acyloin condensations with triazolium-derived carbene catalysts
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It has been shown for the first time that triazolium precatalysts promote (in the presence of base) highly chemoselective crossed acyloin condensation reactions between aliphatic and ortho-substituted aromatic aldehydes. An o-bromine atom can serve as a temporary directing group to ensure high chemoselectivity (regardless of the nature of the other substituents on the aromatic ring) which then can be conveniently removed. The process is of broad scope and is operationally simple as it does not require the preactivation of any of the coupling partners to ensure selectivtiy. Preliminary data indicate that highly enantioselective variants of the reaction are feasible using chiral precatalysts.
- O'Toole, Sarah E.,Rose, Christopher A.,Gundala, Sivaji,Zeitler, Kirsten,Connon, Stephen J.
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supporting information; experimental part
p. 347 - 357
(2011/04/17)
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- Chiral linker 5: scope and limitations of arylsubstituted m-hydrobenzoins as solid supported open chain chiral auxiliaries for diastereoselective syntheses
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The applicability of five aryl substituted m-hydrobenzoin ethers already tested in the L-Selectride mediated stereoselective reduction of phenylglyoxylates as open chain chiral auxiliaries was further investigated via the α-alkylation of propionates, the addition of n-BuZnCl to phenylglyoxylates and the Diels-Alder reaction of acrylates with cyclopentadiene as model reactions. As up to 90% de could be achieved in the solution phase, two optimized auxiliary structures were immobilized on commercially available Wang-resin and applied as a reusable solid supported chiral auxiliaries in the same type of reactions.
- Broeker, Joachim,Knollmueller, Max,Gaertner, Peter
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scheme or table
p. 273 - 287
(2009/09/05)
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- Chiral linker. Part 3: Synthesis and evaluation of aryl substituted m-hydrobenzoins as solid supported open chain chiral auxiliaries for the diastereoselective reduction of α-keto esters
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Five partly novel aryl substituted m-hydrobenzoins were synthesized and the corresponding desymmetrized hydrobenzoin ethers evaluated as open chain chiral auxiliaries in the L-Selectride mediated stereoselective reduction of phenylglyoxylates, resulting in de values of up to 91%. Two optimized auxiliary structures were immobilized on commercially available Wang-resin and applied as a reusable solid supported chiral auxiliary in the same type of reaction.
- Broeker, Joachim,Knollmueller, Max,Gaertner, Peter
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p. 2413 - 2429
(2007/10/03)
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- Reduction of 1,2-diketones with titanium tetraiodide: A simple approach to α-hydroxy ketones
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1,2-Diketones are readily reduced with titanium tetraiodide to give α-hydroxy ketones in good to excellent yields. Regioselectivity on the reduction of unsymmetrical substrates is also discussed. (C) 2000 Elsevier Science Ltd.
- Hayakawa,Sahara,Shimizu
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p. 7939 - 7942
(2007/10/03)
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- Studies on oxygen heterocycles part 2: Synthesis of 2-arylcoumaranones and 2-phenylbenzofuran
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The synthesis of 2-arylcoumaranones and 2-phenyllbenzofuran has been achieved in good yields under acid catalysed conditions from readily accessible and suitably substituted aryl α-diazo-arylmethyl ketones.
- Ghosh, Somnath,Banerjee, Indira,Baul, Susmita
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p. 11537 - 11546
(2007/10/03)
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- Acyl-CoA::cholesterol O-Acyl Transferase (ACAT) Inhibitors. 1. 2-(Alkylthio)-4,5-diphenyl-1H-imidazoles as Potent Inhibitors of ACAT
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A potent, bioavailable ACAT inhibitor may have beneficial effects in the treatment of atherosclerosis by (i) reducing the absorption of dietary cholesterol, (ii) reducing the secretion of very low density lipoproteins into plasma from the liver, and (iii) preventing the transformation of arterial macrophages into foam cells.We have found that a mevalonate derivative 2, which contains a 4,5-diphenyl-1H-imidazol-2-yl moiety, inhibits rat hepatic microsomal ACAT in vitro and produces a significant hypocholesterolemic effect in the cholesterol-fed rat.Structure-activity relationships for analogues of 2 demonstrate that the 4,5-diphenyl-1H-imidazole moiety is a pharmacophore for inhibition of rat microsomal ACAT.
- Harris, Neil V.,Smith, Christopher,Asthon, Michael J.,Bridge, Andrew W.,Bush, Raymond C.,et al.
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p. 4384 - 4392
(2007/10/02)
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- One-pot synthesis of diarylalkylcarbinols and substituted derivatives through carbon monoxide insertion reactions into aryllithiums
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The carbonylation of a THF solution of aryllithium (aryl = Ph, o-anisyl) in the presence of an alkyl bromide, RBr; at atmospheric pressure and -78 deg C, affords diarylalkylcarbinols in good yields.Alkyl chlorides do not react under similar experimental conditions.This feature makes the reaction particularly useful for the synthesisof alcohols functionalized in the alkyl chain through subsequent reactions of the diaryl(chloro)alkylcarbinols.The procedure can also be adapted to afford substituted cyclic ethers.If the reaction is carried out in the presence of dibromoalkanes, only one bromine atom reacts, affording diaryl(bromo)alkylcarbinols which are useful intermediates.With secondary and tertiary alkyl bromides diaryl alkyl ethers are obtained in variable yields.
- Vitale, Arturo A.,Doctorovich, F.,Nudelman, N. Sbarbati
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- Mercury in Organic Chemistry. 26. Synthesis of Heterocycles via Intramolecular Solvomercuration of Aryl Acetylenes
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A number of ortho substituted aryl acetylenes, o-CH3XC6H4YCCR (X=O, S, CO2; Y=-, CO), have been observed to undergo facile intramolecular solvomercuration with mercuric acetate in acetic acid to afford the corresponding benzofuran, benzothiophene, isocoumarin, and chromone organomercuric chlorides, after aqueous sodium chloride workup.The aryl acetylenes m-XC6H4YCH2CCR (X=H, Y=O, R=CH3; X=CH3O, Y=CH2, R=n-C3H7) undergo similar cyclizations to yield mercurated 2H-1-benzopyrans and 1,2-dihydronaphthalenes.The mercuration and subsequent carbonylation of o-R1OC6H4CCR2 1=Si(t-Bu)Me2, R2=CH3; R1=CH3, R2=o-C6H4OCH3> has provided a new approach to the coumarin and coumestan ring systems.
- Larock, Richard C.,Harrison, L. Wayne
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p. 4218 - 4227
(2007/10/02)
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- Preparation and antiinflammatory activity of some nonacidic trisubstituted imidazoles
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A number of trisubstituted imidazoles were made and several found to be potent antiinflammatory agents when examined in the carrageenan rat paw edema test. The antiinflammatory activity of these compounds is retained in adrenalectomized rats. Unlike many previously reported antiinflammatory agents, these compounds are extremely weak acids pK[a] ≥ 11) and are therefore not ionized at physiological pH. One compound, 4,5 bis (4 methoxyphenyl) 2 trifluoromethylimidazole (flumizole), is more potent than indometacin in the rat paw edema test and, in contrast to some related compounds, does not cause photosensitization in mice.
- Lombardino,Wiseman
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p. 1182 - 1188
(2007/10/04)
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