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Photoaromatization of 1,2,3,4-tetrahydroisoquinolines

Irradiation of 1,2,3,4-tetrahydroisoquinolines (1a-d) in the presence of phenanthraquinone or benzophenone affords the corresponding isoquinolines (3a-d) in about 50percent yield.

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NHC-catalyzed Redox-Neutral Aza-Benzoin Reaction of Aldehydes with Tetrahydroisoquinolines

Tetrahydroisoquinoline derivatives are useful synthetic intermediates, which play an important role in the preparation of natural products, pharmaceuticals and other materials. Herein, we report an unprecedented redox-neutral aza-benzoin protocol to construct such scaffold. Upon exposure of tetrahydroisoquinolines to aromatic aldehydes in the presence of an NHC catalyst, the C-1 acylated tetrahydroisoquinolines were obtained in moderate to good yields.

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A unique cobalt(II)-based molecular magnet constructed of hydroxyl/carboxylate bridges with a 3D pillared-layer motif

A new pillared-layer coordination polymer, [Co3(pybz) 2(pico)2]n (1; pybz = 4-(pyridin -4-yl) benzoate, pico = 3-hydroxypicolinate), contains rare 2D [Co3(pico) 2]n2n+ layers formed by linear cobalt(II) trimers through the unusual mu4-kN, O:kO?-mu2 : kO?- mu2 bridging mode of pico ligands, which are further cross-pillared by exotridentate bridging pybz ligands to form a three-dimensional structure with an unusual uninodal 8-connected body-centered-cubic topology. The bulk magnetic behavior of 1 exhibits ferrimagnetic long-range ordering below 2.6 K, which mainly arises from the cooperative magnetic effect of the intra- and intertrimer arrangements in the 2D magnetic system based on the nature of the exchange modes of mu2-hydroxyl, mu2-carboxylate oxygen, and 1, 1, 3-mu3-carboxylate bridges.

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High-performance liquid chromatographic and subcritical fluid chromatographic separation of alpha-arylated ss-carboline, N-alkylated tetrahydroisoquinolines and their bioisosteres on polysaccharide-based chiral stationary phases

New, pharmacologically interesting chiral amino compounds, namely, stereoisomers of alpha-hydroxynaphthyl-ss-carboline, benz[d]azepine and benz[c]azepine analogs as well as N-alpha-hydroxynaphthylbenzyl-substituted isoquinolines were enantioseparated by high-performance liquid chromatographic and subcritical fluid chromatographic methods on polysaccharide-based chiral stationary phases. Separation of the stereoisomers was optimized in both subcritical fluid chromatography and normal phase liquid chromatographic modes by investigating the effects of the composition of the bulk solvent, temperature, and the structures of the analytes and selectors. Both normal phase liquid chromatography and subcritical fluid chromatography exhibited satisfactory performance, albeit with somewhat different effectiveness in the separation of the stereoisomers studied. The optimized methods offer the possibility to apply preparative-scale separations thereby enabling further pharmacological investigations of the enantiomers.

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Top Picks: new discover of 7-Chloro-1,2,3,4-tetrahydroisoquinoline

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Synthesis and further transformations of 8-chloro-3,4-dihydroisoquinoline

Two procedures for the synthesis of barely accessible 8-chloro-3,4-dihydroisoquinoline were investigated. The first approach is based on a directed ortho-lithiation of N-pivaloyl meta-chlorophenylethylamine, followed by formylation and subsequent ring closure under acidic conditions. In the second, more advantageous variant, the N-hydroxyethyl ortho-chlorobenzylamine intermediate undergoes a Friedel-Crafts reaction, and the resulting tetrahydro derivative is oxidized with N-bromosuccinimide. The 8-chloro-3,4-dihydroisoquinoline key intermediate is then applied in Suzuki reactions to give various 8-aryl-3,4-dihydroisoquinolines, which are finally treated with alkyl or aryllithiums to give 1-substituted 8-aryl-1,2,3,4-tetrahydroisoquinolines. These novel 1,2,3,4-tetrahydroisoquinoline derivatives can be used as building blocks in the synthesis of potential drug candidates.

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Awesome and Easy Science Experiments about 2-Methyl-1,2,3,4-tetrahydroisoquinoline

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Synthesis of some N-methyl-1,2,3,4-tetrahydroisoquinolines by Friedel-Crafts cyclisation using benzotriazole auxiliary

1-Hydroxymethylbenzotriazole reacts with phenylethylamines to give the respective N,N-bis(benzotriazol-1-ylmethyl)phenylethylamines, which are then subject to an intramolecular Friedel-Crafts cyclisation at room temperature to yield N-benzotriazol-1-ylmethyl-1,2,3,4-tetrahydroisoquinolines. These crystalline UV- and oxygen-stable products can be reduced at room temperature to the corresponding N-methyl-1,2,3,4-tetrahydroisoquinoIines using NaBH4. The method offers an elegant approach to a wide range of N-methylated 1,2,3,4-tetrahydroisoquinolines since it can be applied not only for the synthesis of 1,2,3,4-tetrahydroisoquinolines with electron-donating substituents on the aromatic moiety, but also for deactivated derivatives. All steps involved work under very mild conditions in high to excellent yields.

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Discovery of 7-Nitro-1,2,3,4-tetrahydroisoquinoline

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Metal-Free Synthesis of Polycyclic Quinazolinones Enabled by a (NH4)2S2O8-Promoted Intramolecular Oxidative Cyclization

An efficient metal-free, (NH4)2S2O8 mediated intramolecular oxidative cyclization for the construction of polycyclic heterocycles was disclosed. A series of polycyclic quinazolinone derivatives with good functional group tolerance were obtained in high yields. The natural products tryptanthrin and rutaecarpine, as well as their derivatives, were easily synthesized by this strategy. A preliminary mechanism study suggested the carbon-centered radical was involved in the catalytic cycle.

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Induced Aggregation and Synergistic Coordination Strategy in Cluster Organic Architectures

ConspectusDevelopments in strategies for the synthesis of oxo-hydroxo lanthanide (Ln) clusters during the past few decades have resulted in abundant relevant crystalline materials that exhibit attractive structures and interesting properties. The combination of these oxo-hydroxo Ln clusters and organic ligands has led to the formation of new extended arrays of Ln cluster organic frameworks (LnCOFs). In contrast to metal-organic frameworks, the incorporation of particular characteristics of clusters provides the opportunity to develop performances not available in single-metal compounds. Even with steady advances in oxo-hydroxo Ln clusters, progress in LnCOFs is less developed.To obtain LnCOFs, one premise is to induce the oxophilic Ln ions undergoing aggregation. Meanwhile, the organic ligands should have extra coordination sites for further expansion. Multidentate organic ligands like pyrazinecarboxylic acid and pyridinecarboxylic acid containing O and N donors will meet these two requirements. Their carboxyl groups will induce the aggregation of Ln ions, while the N donors can serve as potential extension sites. To make more open frameworks or if the oxo-hydroxo Ln clusters fail to be congregated or connected, then a second ligand is necessary. The introduction of the suitable second ligand may occupy a partial coordination sphere of Ln ions and ultimately benefit the connection process.In this Account, we introduce the origin and evolution of the induced aggregation and synergistic coordination strategy. According to the attributes of the organic ligands in the documented LnCOFs, we classify them into linear and nonlinear groups in the second and third parts. From the aspect of ligand-induced aggregation, isonicotinic acid (HIN) and lengthened 4-(4-pyridyl)benzoic acid (HPBA) ligands as well as their nonlinear analogues are settled as typical models. From the aspect of synergistic coordination, chelating ligands like 1,2-benzenedicarboxylic acid (1,2-H2BDC) and acetic acid (HOAc) play significant roles. Moreover, three types of synergistic coordination are discussed in detail: synergistic coordination between two types of organic ligands, synergistic coordination between organic and inorganic ligands, and simultaneous synergistic coordination of aforementioned two types. From the aspect of LnCOF products, in addition to traditional pure LnCOFs, new types of heterometallic frameworks containing two types of cluster building units have been developed.Although this Account focuses on the nuclearity and coordination aspects of LnCOFs, we anticipate that it will stimulate more efforts in the further study of their properties beyond the exploratory synthesis. More importantly, synergistic coordination may be applied to other systems and inspire crystal design and targeted assembly of new functional materials.

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Novel ofloxacin derivatives: Synthesis, antimycobacterial and toxicological evaluation

Thirty novel 9-fluoro-2,3-dihydro-8,10-(mono/di-sub)-3-methyl-8-nitro-7-oxo-7H-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxylic acids were synthesized from 2,3,4,5-tetrafluoro benzoic acid and evaluated for in vitro and in vivo antimycobacterial activities against Mycobacterium tuberculosis H37Rv (MTB), multi-drug resistant Mycobacterium tuberculosis (MDR-TB), and Mycobacterium smegmatis (MC2) and also tested for the ability to inhibit the supercoiling activity of DNA gyrase from mycobacteria. Among the synthesized compounds, 10-[2-carboxy-5,6-dihydroimidazo[1,2-a]pyrazin-7(8H)-yl]-9-fluoro-2,3-dihydro-3-methyl-8-nitro-7-oxo-7H-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxylic acid was found to be the most active compound in vitro with MIC99 of 0.19 muM and 0.09 muM against MTB and MTR-TB, respectively. In the in vivo animal model also the same compound decreased the bacterial load in lung and spleen tissues with 1.91 and 2.91 – log 10 protections, respectively, at the dose of 50 mg/kg body weight. Compound 10-[(4-((4-chlorophenyl)(phenyl)methyl)piperazin-1-yl)]-9-fluoro-2,3-dihydro-3-methyl-8-nitro-7-oxo-7H-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxylic acid was found to be the most active in the inhibition of the supercoiling activity of DNA gyrase with an IC50 of 10.0 mug/mL. The results demonstrate the potential and importance of developing new oxazino quinolone derivatives against mycobacterial infections.

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Discovery of new potent dual sigma receptor/GluN2b ligands with antioxidant property as neuroprotective agents

Among several potential applications, sigma receptors (sigmaRs) can be used as neuroprotective agents, antiamnesic, antipsychotics and against other neurodegenerative disorders. On the other hands, antagonists of the GluN2b-subunit-containing-N-methyl-D-aspartate (NMDA) receptors are of major interest for the same purpose, being this subunit expressed in specific areas of the central nervous system and responsible for the excitatory regulation of nerve cells. Under these premises, we have synthesized and biologically tested novel hybrid derivatives obtained from the combination of phenyloxadiazolone and dihydroquinolinone scaffolds with different amine moieties, peculiar of sigma2R ligands. Most of the new ligands exhibited a pan-affinity towards both sigmaR subtypes and high affinity against GluN2b subunit. The most promising compounds belong to the dihydroquinolinone series, with the best affinity profile for the cyclohexylpiperazine derivative 28. Investigation on their biological activity showed that the new compounds were able to protect SH-SY5Y cells against oxidative stress induced by hydrogen peroxide treatment. These results proved that our dual sigmaR/GluN2b ligands have beneficial effects in a model of neuronal oxidative stress and can represent strong candidate pharmacotherapeutic agents for minimizing oxidative stress-induced neuronal injuries.

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