- Tandem Oxidative Phenol Dearomatization/Formal [3+2] Annulation Protocol en Route to Highly Functionalized Benzothiophenes
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A new strategy for the synthesis of benzothiophenes through formal [3+2] annulation of sulfanylacetaldehyde and cyclohexa-2,4-dien-1-one monoketals has been developed. This approach relies on the ease of aromatization of tetrahydrobenzothiophenone derivatives prepared by the aforementioned protocol. Given the ready accessibility of various substituted cyclohexa-2,4-dien-1-one monoketals, a range of benzothiophene derivatives became available.
- Chittimalla, Santhosh Kumar,Bandi, Chennakesavulu
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Read Online
- Total synthesis of the isoquinolinium metabolite ETM-204 of Trabectidin
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Ecteinascidin-743 (Trabectidin, Trabectedin, Yondelis) is a synthetically obtained pharmaceutical drug originally isolated from a marine tunicate. Trabectedin is used for the chemotherapy of soft-tissue sarcoma and ovarian cancer. Th
- Breinbauer, Rolf,Gissing, Simon,Lembacher-Fadum, Christian,Pour, Georg
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- Role of Catalyst Support's Physicochemical Properties on Catalytic Transfer Hydrogenation over Palladium Catalysts
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Catalytic transfer hydrogenation (CTH) is a promising reaction for valorisation of bio-based feedstocks via hydrogenation without needing to use H2. Unlike standard hydrogenation, CTH occurs via dehydrogenation (DHD) of a hydrogen donor (H-donor) and hydrogenation (HYD) of a substrate. Therefore, the “ideal” CTH catalyst must balance the catalysis of both reactions to maximize the hydrogen transfer between H-donor and substrate with minimal H2 loss to gas (high atom efficiency). Additionally, the H-donor must be highly stable to prevent secondary reactions with the substrate. Herein we study the impact of the catalyst's properties on CTH of guaiacol using bicyclohexyl, a liquid organic hydrogen carrier, as a H-donor. The reaction was promoted by palladium dispersed on three typical support materials (γ-Al2O3, MgO, and SiO2). The performance of these catalysts in the conversion of bicyclohexyl and guaiacol was evaluated, allowing to estimate the H-transfer efficiency, as well as the potential for recycling the spent H-donor (bicyclohexyl). The apparent activation energies for DHD of bicyclohexyl and HYD of guaiacol revealed that slow DHD combined with fast HYD, as is the case with Pd/MgO, favours hydrogen transfer efficiency and selectivity towards hydrogenated products. In addition, an investigation of the DHD of bicyclohexyl and HYD of guaiacol independently showed that the affinity between the organic molecules and the support significantly impacts CTH. Indeed, Pd/SiO2 was highly active for both reactions individually and almost inactive for CTH. Consequently, these findings highlight the importance of the interaction between solvent-substrate-support in designing catalysts for transfer hydrogenation.
- Batalha, Nuno,Fraga, Gabriel,Hasan, M. D.,Konarova, Muxina,Laycock, Bronwyn,Pratt, Steven,Santos, Mirella S.
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p. 5191 - 5202
(2021/10/29)
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- SUBSTITUTED-N-HETEROARYL COMPOUNDS AND USES THEREOF
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The present disclosure relates generally to compounds useful for the treatment and/or enhancement of cognitive function and negative symptoms associated with central nervous system disorders where the circuitry involving fast spiking PV+ interneurons and the production of cortical gamma oscillations is disrupted. The subject disclosure enables the manufacture of medicaments as well as compositions containing same for use in methods of therapy and prophylaxis of cognitive dysfunction and negative symptoms.
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Page/Page column 63; 77
(2020/01/24)
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- SUBSTITUTED-PYRIDINYL COMPOUNDS AND USES THEREOF
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The present application relates generally to compounds useful for the treatment and/or enhancement of cognitive dysfunction and negative symptoms associated with CNS disorders where the circuitry involving fast spiking PV+ interneurons and the production of cortical gamma oscillations is disrupted. The subject disclosure enables the manufacture of medicaments as well as compositions containing same for use in methods of therapy and prophylaxis of cognitive dysfunction and negative symptoms.
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Page/Page column 37; 91-92
(2020/01/10)
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- Tuning the Reactivity of Peroxo Anhydrides for Aromatic C-H Bond Oxidation
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Phenol moieties are key structural motifs in many areas of chemical research from polymers to pharmaceuticals. Herein, we report on the design and use of a structurally demanding cyclic peroxide (spiro[bicyclo[2.2.1]heptane-2,4′-[1,2]dioxolane]-3′,5′-dione, P4) for the direct hydroxylation of aromatic substrates. The new peroxide benefits from high thermal stability and can be synthesized from readily available starting materials. The aromatic C-H oxidation using P4 exhibits generally good yields (up to 96%) and appreciable regioselectivities.
- Pilevar, Afsaneh,Hosseini, Abolfazl,?ekutor, Marina,Hausmann, Heike,Becker, Jonathan,Turke, Kevin,Schreiner, Peter R.
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p. 10070 - 10079
(2018/09/06)
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- Examination of Selectivity in the Oxidation of ortho- and meta-Disubstituted Benzenes by CYP102A1 (P450 Bm3) Variants
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Cytochrome P450 CYP102A1 (P450 Bm3) variants were used to investigate the products arising from the P450 catalysed oxidation of a range of disubstituted benzenes. The variants used all generated increased levels of metabolites compared to the wild-type enzyme. With ortho-halotoluenes up to six different metabolites could be identified whereas the oxidation of 2-methoxytoluene generated only two aromatic oxidation products. Addition of an ethyl group markedly shifted the selectivity for oxidation to the more reactive benzylic position. Epoxidation of an alkene was also preferred to aromatic oxidation in 2-methylstyrene. Significant minor products arising from the migration of one substituent to a different position on the benzene ring were formed during certain P450-catalysed substrate turnovers. For example, 2-bromo-6-methylphenol was formed from the turnover of 2-bromotoluene and the dearomatisation product 6-ethyl-6-methylcyclohex-2,4-dienone was generated from the oxidation of 2-ethyltoluene. The RLYF/A330P variant altered the product distribution enabling the generation of certain metabolites in higher quantities. Using this variant produced 4-methyl-2-ethylphenol from 3-ethyltoluene with ≥90 % selectivity and with a biocatalytic activity suitable for scale-up of the reaction.
- Munday, Samuel D.,Dezvarei, Shaghayegh,Lau, Ian C.-K.,Bell, Stephen G.
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p. 2512 - 2522
(2017/07/12)
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- α-Halogenation as a Strategy to Functionalize Cyclohexa-2,4-dienones
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A facile pyridine-mediated α-halogenation approach to functionalize cyclohexa-2,4-dienones is developed. A range of reactions, including organometallic coupling protocols, have been applied on these newly obtained halogenated cyclohexa-2,4-dienones, and the results are presented herein.
- Chittimalla, Santhosh Kumar,Koodalingam, Manikandan,Gadi, Vinod Kumar,Anaspure, Prasad
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p. 475 - 480
(2017/02/24)
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- Access to 3-arylindoles through a tandem one-pot protocol involving dearomatization, a regioselective michael addition reaction, and rearomatization
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A facile, general and rapid protocol for the introduction of oxygenated aryls at the 3-position of indoles is described. This approach consists of a tandem dearomatization, a regioselective Michael addition reaction, and rearomatization in a one-pot three-step sequence to obtain 3-arylindoles in good yields. A non-metal mediated detour method for installing oxygenated aryls at the 3-position of indoles is described. Copyright
- Chittimalla, Santhosh Kumar,Bandi, Chennakesavulu,Putturu, Sireesha,Kuppusamy, Rajesh,Boellaard, Kevin Christopher,Tan, David Chu Aan,Lum, Demi Ming Jie
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p. 2565 - 2575
(2014/05/06)
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- Facile and regioselective dealkylation of alkyl aryl ethers using niobium(V) pentachloride
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A simple and facile method for the cleavage of carbon-oxygen bonds promoted by niobium pentachloride(V) is described. Excellent yields and regioselectivities were observed with various alkyl aryl ethers to give the phenols. NMR studies revealed the formation of monoaryloxy niobium salt(V), and a neighboring-group effect may play a significant role in the regioselectivity. Wiley-VCH Verlag GmbH & Co. KGaA, 2006.
- Sudo, Yukinori,Arai, Shigeru,Nishida, Atsushi
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p. 752 - 758
(2007/10/03)
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- A simple and regioselective carbon-oxygen bond cleavage using Niobium(V)
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A simple and convenient method for the differentiation of alkoxy groups on aromatic rings is described. Niobium(V) is found to possess a strong Lewis acid property to transform alkyl arylethers smoothly to the corresponding phenols in high yields. The excellent regioselectivity was also observed in dialkoxy benzene derivatives under mild conditions.
- Arai, Shigeru,Sudo, Yukinori,Nishida, Atsushi
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p. 1104 - 1106
(2007/10/03)
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- A concise route to 3-hydroxy-4-methoxy-5-methylbenzaldehyde derivative
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3-Hydroxy-4-methoxy-5-methylbenzaldehyde derivative (1c) has been synthesized in 7 steps from 2,3-dihydroxytoluene (4). An isopropyl derivative has been used to protect a phenol during this transformation. The overall yield of 1c was 37%.
- Saito, Naoki,Tachi, Masashi,Seki, Ryu-Ichi,Sugawara, Yayoi,Takeuchi, Eri,Kubo, Akinori
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p. 2407 - 2421
(2007/10/03)
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- Transition metal complexes in organic synthesis, part 43: First total synthesis of the free radical scavenger (±)-neocarazostatin B via iron- and nickel-mediated coupling reactions
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The first total synthesis of the naturally occurring free radical scavenger (±)-neocarazostatin B is described by using a one-pot iron- mediated construction of the carbazole skeleton and a nickel-mediated prenylation as the key-steps.
- Knoelker, Hans-Joachim,Froehner, Wolfgang,Wagner, Alfred
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p. 2947 - 2950
(2007/10/03)
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- Skin sensitization to eugenol and isoeugenol in mice: Possible metabolic pathways involving ortho-quinone and quinone methide intermediates
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With the aim of providing further mechanistic insights into the mode of action of eugenol (4-allyl-2-methoxyphenol) and isoeugenol (4-propenyl-2- methoxyphenol), we have synthesized two series of modified compounds which were tested in the mouse local lym
- Bertrand, Franck,Basketter, David A.,Roberts, David W.,Lepoittevin, Jean-Pierre
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p. 335 - 343
(2007/10/03)
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- Sodium Bis(trimethylsily)amide and Lithium Diisopropylamide in Deprotection of Alkyl Aryl Ethers: α-Effect of Silicon
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Removal of methyl, benzyl, and methylene groups from alkyl aryl ethers is among the most popular deprotecting methods in organic synthesis. Alkali organoamides NaN(SiMe3)2 and LiN(i-Pr)2, often used as organic bases, have been developed as efficient deprotecting agents. Treatment of aryl methyl ethers with 1.5 equiv of NaN(SiMe3)2 or LiN(i-Pr)2 in THF and 1,3-dimethyl-2-imidazolidinone in a sealed tube at 185 °C produced the corresponding phenol derivatives in good to excellent yields (80-97percent). Removal of the methylene unit from benzodioxole derivatives was also accomplished by use of 2.5 equiv of these alkali organoamides. The corresponding catechols were obtained in 93-99percent yields. The activity of NaN(SiMe3)2 was proven lower than that of LiN(i-Pr)2; it is due to the steric congestion and the α-stabilizing effect of the silyl groups. Thus selective mono-O-demethylation of o-dimethoxybenzenes can be achieved by the use of NaN(SiMe3)2 but not LiN(i-Pr)2. O-Debenzylation of aryl benzyl ethers, however, can be accomplished by the use of LiN(i-Pr)2.
- Hwu, Jih Ru,Wong, Fung Fuh,Huang, Jiann-Jyh,Tsay, Shwu-Chen
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p. 4097 - 4104
(2007/10/03)
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- Tobacco smoke chemistry. 2. Alkyl and alkenyl substituted guaiacols found in cigarette smoke condensate.
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A series of alkyl and alkenyl substituted guaiacols, which comprise a group of biologically and organoleptically active compounds, have been synthesized. Mass spectra and GC retention times for these have been recorded and compared with those obtained for constituents of a weakly acidic fraction of smoke condensate derived from American blend type cigarettes. On the basis of these results, 25 guaiacols have been identified, 18 of which have not been detected in tobacco smoke condensate previously.
- Arnarp,Bielawski,Dahlin,Dahlman,Enzell,Pettersson
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- Oxidation of Methoxy- and/or Methyl-Substituted Benzenes and Naphthalenes to Quinones and Phenols by H2O2 in HCOOH
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The oxidation of a number of arenes (methoxybenzenes, methylbenzenes, and naphthalenes) to quinones and phenols by H2O2 in HCOOH has been examined.Methoxybenzenes were much more easily oxidized to p-benzoquinones than methylbenzenes (e.g., 1,3,5-trimethoxybenzene was oxidized to 2,6-dimethoxy-p-benzoquinone in a 75percent yield and 1,2,4-trimethylbenzene to 2,3,5-trimethyl-p-benzoquinone in a 16percent yield).Electron-withdrawing substituents, such as nitro, cyano, and chloro groups, lowered the conversion of reactants and changed the product selectivity from quinones to phenols.Methoxybenzonitriles were oxidized to corresponding phenols in a moder ate yield (e.g., 2,6-dimethoxybenzonitrile to 3-hydroxy-2,6-dimethoxybenzonitrile in a 39percent yield and a 64percent selectivity).
- Orita, Hideo,Shimizu, Masao,Hayakawa, Takashi,Takehira, Katsuomi
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p. 1652 - 1657
(2007/10/02)
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