- An unexpected double-bond isomerization catalyzed by Crabtree's iridium(I) catalyst
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The first iridium-catalyzed isomerization of an exocyclic into an endocyclic double bond is described. A mechanism is proposed for this reaction. Crabtree's catalyst thus allows the migration of a double bond that does not occur under classical conditions. Georg Thieme Verlag Stuttgart.
- Krel, Michael,Lallemand, Jean-Yves,Guillou, Catherine
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- Synthesis and Dopaminergic Activity of 2-Substituted Octahydrobenzoquinolines
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A series of 2-substituted octahydrobenzoquinolines has been synthesized and assayed for dopamine agonist activity.Only the compounds corresponding to the β-rotameric conformation of dopamine showed biphasic activity in competition binding studies with the radioligand spiroperidol.These findings suggest that the congeners possessing the β-rotamer conformation show receptor-binding characteristics that resemble those of the ergolines more closely than do those of the corresponding α-rotamer congeners.
- Craig, J. Cymerman,Torkelson, Steven M.,Findell, Paul R.,Weiner, Richard I.
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Read Online
- Synthesis method of 5-methoxy-2-tetralone
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The invention discloses a synthesis method of 5-methoxy-2-tetralone, the synthesis method comprises the following steps: reacting 3-methoxyphenylacetic acid with thionyl chloride in the presence of a catalyst solvent to obtain a reaction product containin
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Paragraph 0032; 0036-0037; 0038; 0042-0043; 0044; 0048-0049
(2021/08/11)
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- Optical Control of Dopamine Receptors Using a Photoswitchable Tethered Inverse Agonist
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Family A G protein-coupled receptors (GPCRs) control diverse biological processes and are of great clinical relevance. Their archetype rhodopsin becomes naturally light sensitive by binding covalently to the photoswitchable tethered ligand (PTL) retinal. Other GPCRs, however, neither bind covalently to ligands nor are light sensitive. We sought to impart the logic of rhodopsin to light-insensitive Family A GPCRs in order to enable their remote control in a receptor-specific, cell-type-specific, and spatiotemporally precise manner. Dopamine receptors (DARs) are of particular interest for their roles in motor coordination, appetitive, and aversive behavior, as well as neuropsychiatric disorders such as Parkinson's disease, schizophrenia, mood disorders, and addiction. Using an azobenzene derivative of the well-known DAR ligand 2-(N-phenethyl-N-propyl)amino-5-hydroxytetralin (PPHT), we were able to rapidly, reversibly, and selectively block dopamine D1 and D2 receptors (D1R and D2R) when the PTL was conjugated to an engineered cysteine near the dopamine binding site. Depending on the site of tethering, the ligand behaved as either a photoswitchable tethered neutral antagonist or inverse agonist. Our results indicate that DARs can be chemically engineered for selective remote control by light and provide a template for precision control of Family A GPCRs.
- Donthamsetti, Prashant C.,Winter, Nils,Sch?nberger, Matthias,Levitz, Joshua,Stanley, Cherise,Javitch, Jonathan A.,Isacoff, Ehud Y.,Trauner, Dirk
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p. 18522 - 18535
(2018/01/08)
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- Anti-Markovnikov Oxidation of β-Alkyl Styrenes with H2O as the Terminal Oxidant
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Oxygenation of alkenes is one of the most straightforward routes for the construction of carbonyl compounds. Wacker oxidation provides a broadly useful strategy to convert the mineral oil into higher value-added carbonyl chemicals. However, the conventional Wacker chemistry remains problematic, such as the poor activity for internal alkenes, the lack of anti-Markovnikov regioselectivity, and the high cost and chemical waste resulted from noble metal catalysts and stoichiometric oxidant. Here, we describe an unprecedented dehydrogenative oxygenation of β-alkyl styrenes and their derivatives with water under external-oxidant-free conditions by utilizing the synergistic effect of photocatalysis and proton-reduction catalysis that can address these challenges. This dual catalytic system possesses the single anti-Markovnikov selectivity due to the property of the visible-light-induced alkene radical cation intermediate.
- Zhang, Guoting,Hu, Xia,Chiang, Chien-Wei,Yi, Hong,Pei, Pengkun,Singh, Atul K.,Lei, Aiwen
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supporting information
p. 12037 - 12040
(2016/09/28)
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- Synthesis and biological evaluation of 1-benzylidene-3,4-dihydronaphthalen- 2-one as a new class of microtubule-targeting agents
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A series of 1-benzylidene-3,4-dihydronaphthalen-2-one derivatives were designed and synthesized, and their biological activities in vitro and in vivo were evaluated. The results showed a number of the title compounds exhibiting potent nanomolar activity in several human cancer cell lines. Of these, compound 22b showed the strongest inhibitory activity against human CEM, MDA-MBA-435, and K562 cells (IC50 = 1 nM), displayed in vitro inhibition of tubulin polymerization (IC50 = 3.93 μM), and significantly induced cell cycle arrest in G2/M phase. In addition, compound 22b could inhibit the tumor growth in colon nude mouse xenograft tumor model significantly and seemed safer than CA-4 when achieving a similar tumor suppression. This study provided a new molecular scaffold for the further development of antitumor agents that target tubulin.
- Liu, Jia,Zheng, Can-Hui,Ren, Xiao-Hui,Zhou, Feng,Li, Wei,Zhu, Ju,Lv, Jia-Guo,Zhou, You-Jun
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p. 5720 - 5733
(2012/07/30)
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- Adenosine A2A receptor-antagonist/dopamine D2 receptor-agonist bivalent ligands as pharmacological tools to detect A 2A-D2 receptor heteromers
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Adenosine A2A (A2AR) and dopamine D2 (D2R) receptors mediate the antagonism between adenosinergic and dopaminergic transmission in striatopallidal GABAergic neurons and are pharmacological targets for the treatment of Parkinson's disease.Here, a family of heterobivalent ligands containing a D2R agonist and an A 2AR antagonist linked through a spacer of variable size was designed and synthesized to study A2AR-D2R heteromers. Bivalent ligands with shorter linkers bound to D2R or A2AR with higher affinity than the corresponding monovalent controls in membranes from brain striatum and from cells coexpressing both receptors. In contrast, no differences in affinity of bivalent versus monovalent ligands were detected in experiments using membranes from cells expressing only one receptor. These findings indicate the existence of A2AR-D2R heteromers and of a simultaneous interaction of heterobivalent ligands with both receptors. The cooperative effect derived from the simultaneous interaction suggests the occurrence of A2AR-D2R heteromers in cotransfected cells and in brain striatum. The dopamine/adenosine bivalent action could constitute a novel concept in Parkinson's disease pharmacotherapy.
- Soriano, Aroa,Ventura, Ruben,Molero, Anabel,Hoen, Rob,Casado, Vicent,Corte, Antoni,Fanelli, Francesca,Albericio, Fernando,Lluís, Carmen,Franco, Rafael,Royo, Miriam
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supporting information; experimental part
p. 5590 - 5602
(2010/03/24)
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- A concise method for the synthesis of 2-tetralone by titanium tetrachloride-promoted cyclization of 4-aryl-2-hydroxybutanal diethyl acetal
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4-Aryl-2-hydroxybutanal diethyl acetal, prepared from the reaction of benzyl Grignard reagent and glycidaldehyde diethyl acetal, was treated with titanium tetrachloride to give 2-tetralone in good yield. This highly efficient transformation involves tande
- Hon, Yung-Son,Devulapally, Rammohan
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scheme or table
p. 5713 - 5715
(2009/12/09)
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- TiCl4-promoted intramolecular cyclization of 4-methoxy-5-arylethyl-1,3-dioxolan-2-ones: an expedient method to prepare 2-tetralones
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DABCO is a very effective catalyst in the formation of 4-methoxy-5-arylethyl-1,3-dioxolan-2-ones 12 from the corresponding α-carbonatoaldehyde. Intramolecular cyclization of cyclic carbonates 12 promoted by TiCl4 affords 2-tetralones 13 contain
- Hon, Yung-Son,Devulapally, Rammohan
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experimental part
p. 2831 - 2834
(2009/09/30)
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- Synthesis and antifungal activities of novel 2-aminotetralin derivatives
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Novel 2-aminotetralin derivatives were synthesized as antifungal agents. The 2-aminotetralin scaffold was chemically designed to mimic the tetrahydroisoquinoline ring of the lead molecule described before. Their antifungal activities were evaluated in vitro by measuring the minimal inhibitory concentrations (MICs). Compounds 10a, 12a, 12c, 13b, and 13d are more potent than fluconazole against seven testing human fungal pathogens. Compound 10b exhibits much higher antifungal activities against all of the four fluconazole-resistant clinic Candida albicans strains than the control drugs including amphotericin B, terbinafine, ketoconazole, and itraconazole. The mode of action of some compounds to the potential receptor lanosterol 14α-demethylase (CYP51) was investigated by molecular docking. The studies presented here provide a new structural type for the development of novel antifungal compounds. Furthermore, 10b was evaluated in vivo by a rat vaginal candidiasis model, and it was found that 10b significantly decreases the number of fungal colony counts.
- Yao, Bin,Ji, Haitao,Cao, Yongbin,Zhou, Youjun,Zhu, Jü,Lü, Jiaguo,Li, Yaowu,Chen, Jun,Zheng, Canhui,Jiang, Yuanying,Liang, Rongmei,Tang, Hui
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p. 5293 - 5300
(2008/03/18)
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- Dynamic equilibria in the products of intramolecular buchner additions of diazoketones to aryl rings bearing methoxy substituents
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Rhodium carboxylate catalyzed aromatic addition reactions of a range of diazoketones bearing methoxy-substituted aryl rings have been explored. While the existence of norcaradiene-cycloheptatriene equilibria in related compounds is well established, the aromatic addition products in this study display more complex dynamic equilibria due to conjugation with the methoxy group; the experimental evidence for this is discussed in detail. In the azulenone products 21-26 derived from p-methoxy-substituted diazoketones 14-16, the diastereomers interconvert via a spiro intermediate 39. A related mechanistic process in the azulenones 43-46 derived from the o-methoxy-substituted diazoketones 17, 18 interconverts regioisomers, explaining the conflicting reports for the regioselectivity of the cyclization of diazoketone 1. With the m-methoxy-substituted diazoketone 19, involvement of the methoxy group through a different pathway results in fragmentation of the azulenone to form the tetralone 47. With the azulenones 21-26 exclusive trapping of the norcaradiene associated with the less thermodynamically stable diastereomers in a cycloadduct with N-phenylmaleimide is observed. Due to the presence of the activating methoxy substituent on the aromatic ring, the aromatic addition reactions of the diazoketones studied were not very sensitive to the nature of the rhodium catalyst.
- Maguire,O'Leary,Harrington,Lawrence,Blake
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p. 7166 - 7177
(2007/10/03)
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- Practical and large-scale synthesis of rac-(3S,4aR,10aR)-6-methoxy-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g] quinoline-3-carboxylic acid methyl Ester
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3-Substituted octahydrobenzo[g]quinolines are important intermediates for pharmaceutically active compounds. A short, efficient synthesis, which is feasible for large-scale manufacturing of rac-(3S,4aR,10aR)-6-methoxy-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[g] quinoline-3-carboxylic acid methyl ester is presented. As starting materials the cheap and readily available 1,6-dimethoxynaphthalene and ethoxymethylenecyanoacetic acid ethyl ester were chosen. All atoms of the skeleton were introduced in the first step, by the reaction of 7-lithiated 1,6-dimethoxynaphthalene with ethoxymethylenecyanoacetic acid ethyl ester. Subsequent hydrogenation, followed by Birch reduction and acidic cyclization gave the 6-methoxy-2,3,4,4a,5,-10-hexahydrobenzo[g]quinoline-3-carboxylic acid·hydrochloride in high yield. The trans fusion of the two six-membered rings was established after NaBH4 reduction. After esterification, n-propylation, and kinetic protonation of an intermittantly formed trimethylsilylketene acetal, the desired product was isolated in high yield and excellent purity.
- B?nziger, Markus,Cercus, Jacques,Stampfer, Wolfgang,Sunay, Ustun
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p. 460 - 466
(2013/08/07)
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- The preparation and biological activity of lactam-based, non-steroidal, inhibitors of human type-1 steroid 5α-reductase
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A Beckmann rearrangement of cis- and trans-fused 3,4,4a,9,10,10a-hexahydrophenanthren-1(2H)-one oximes has yielded three azepines. An in vitro assay of the azepines and (3aSR,9bSR)-6-methoxy-3-methyl-1,3,3a,4,5,9b-hexahydro-2H-benz[e]indol-2-one, prepared in four steps from naphthalene-1,6-diol, against human type-1 steroid 5α-reductase, revealed the tricyclic five-membered lactam to be a potent inhibitor (IC50 733 nM).
- Abell, Andrew D.,Phillips, Andrew J.,Budhia, Sangeeta,McNulty, Ann M.,Neubauer, Blake L.
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p. 389 - 396
(2007/10/03)
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- 2-Amido-8-methoxytetralins: A Series of Nonindolic Melatonin-like Agents
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A series of unsubstituted and methoxy-substituted 2-amidotetralins (4a-q) was prepared and evaluated for their ability to complete for 2-iodomelatonin binding to chicken retinal membranes and for their potency to inhibit the calcium-dependent release of dopamine from rabbit retina.The lead compound, 2-acetamido-8-methoxytetralin (4j), showed a moderate affinity (Ki = 46 nM) and potency (IC50 = 1.4 nM) at the melatonin receptor.The structural requirements necessary for optimal agonistic activity at the melatonin receptor are as follows.First, the amido group, which should have a small, nonbranched alkyl group, is essential for affinity, and second, the methoxy substituent at the 8-position of the 2-amidotetralin ring is essential for optimal agonistic activity at the melatonin receptor.We concluded that this series of unsubstituted and methoxy-substituted 2-amidotetralins constitutes a class of nonindolic melatonin-like agents that can be used as pharmacological tools to further characterize melatonin receptors and to elucidate the mode of action of melatonin.
- Copinga, Swier,Tepper, Pieter G.,Grol, Cor J.,Horn, Alan S.,Dubocovich, Margarita L.
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p. 2891 - 2898
(2007/10/02)
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- A Reinvestigation of the Intramolecular Buchner Reaction of 1-Diazo-4-phenylbutan-2-ones Leading to 2-Tetralones
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Rhodium acetate-catalysed decomposition of 1-diazo-4-(2-methoxyphenyl)butan-2-one 8 leads, after rearrangement under acidic conditions, to 5-methoxy-2-tetralone 13 and not to 8-methoxy-2-tetralone 10 as reported.
- Cordi, Alex A.,Lacoste, Jean-Michel,Hennig, Philippe
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- STUDIES ON OXYGEN HETEROCYCLES PART-1 : ACID CATALYSED AND PHOTOCHEMICAL REACTIONS OF SOME ARYLDIAZOKETONES
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Trifluoroacetic acid catalysed reaction of 2-methoxyphenyldiazomethylketone (4a), 2-acetoxyphenyldiazomethylketone (4b) and 3-(2-anisyl)-α-diazo-2-propanone (11) leads to the formation of coumaranone (6) and 3-chromanone (12), while 4-(2-anisyl)-α-diazo-2-butanone (16) affords benzo-1-oxepan-3-one (17) and 5-methoxy-2-tetralone (18) in moderate yield.The photochemical decomposition of the said diazoketones (4a, 11 and 16) gave products depending on the length of the side chain present in the substrates.
- Ghosh, Somnath,Datta, Indira,Chakraborty, Rupak,Das, Tapas Kumar,Sengupta, Judhajit,Sarkar, Dipak Chandra
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p. 1441 - 1446
(2007/10/02)
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- ENANTIOSELECTIVE PREPARATION OF KEY INTERMEDIATES FOR STEROID SYNTHESIS THROUGH THE ASYMMETRIC MICHAEL ADDITION PROCESS INVOLVING CHIRAL IMINES.
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(S)-Phenanthrone 7, prepared from ketone 4 (80 percent yield, 93 percent ee), was transformed into compounds 8, 9, 13, 15 and 16, useful intermediates in steroid synthesis.
- d'Angelo, Jean,Revial, Gilbert,Volpe, Tony,Pfau, Michel
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p. 4427 - 4430
(2007/10/02)
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- Simple Preparation of β-Tetralones and β-Indanones by a 1,2-Carbonyl Group Transposition
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By a four-step procedure, the ketones 3 are converted into the β-tetralones 7a-d and the β-indanones 7e, f via the intermediates 4, 5, and 6.
- Braun, Manfred,Bernhard, Carlo
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p. 435 - 437
(2007/10/02)
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