- Synthesis of an Isotopically Labeled Naphthalene Derivative That Supports a Long-Lived Nuclear Singlet State
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The synthesis of an octa-alkoxy substituted isotopically labeled naphthalene derivative, shown to have excellent properties in singlet NMR experiments, is described. This highly substituted naphthalene system, which incorporates an adjacent 13C spin pair, is readily accessed from a commercially available 13C2-labeled building block via sequential thermal alkynyl- and arylcyclobutenone rearrangements. The synthetic route incorporates a simple desymmetrization approach leading to a small difference in the chemical shifts of the 13C spin pair, a design constraint crucial for accessing nuclear singlet order. (Chemical Equation Presented).
- Hill-Cousins, Joseph T.,Pop, Ionut-Alexandru,Pileio, Giuseppe,Stevanato, Gabriele,H?kansson, P?r,Roy, Soumya S.,Levitt, Malcolm H.,Brown, Lynda J.,Brown, Richard C. D.
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- Polygala tenuifolia-Acori tatarinowii herbal pair as an inspiration for substituted cinnamic α-asaronol esters: Design, synthesis, anticonvulsant activity, and inhibition of lactate dehydrogenase study
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Inspired by the traditional Chinese herbal pair of Polygala tenuifolia-Acori Tatarinowii for treating epilepsy, 33 novel substituted cinnamic α-asaronol esters and analogues were designed by Combination of Traditional Chinese Medicine Molecular Chemistry (CTCMMC) strategy, synthesized and tested systematically not only for anticonvulsant activity in three mouse models but also for LDH inhibitory activity. Thereinto, 68–70 and 75 displayed excellent and broad spectra of anticonvulsant activities with modest ability in preventing neuropathic pain, as well as low neurotoxicity. The protective indices of these four compounds compared favorably with stiripentol, lacosamide, carbamazepine and valproic acid. 68–70 exhibited good LDH1 and LDH5 inhibitory activities with noncompetitive inhibition type, and were more potent than stiripentol. Notably, 70, as a representative agent, was also shown as a moderately positive allosteric modulator at human α1β2γ2 GABAA receptors (EC50 46.3 ± 7.3 μM). Thus, 68–70 were promising candidates for developing into anti-epileptic drugs, especially for treatment of refractory epilepsies such as Dravet syndrome.
- Bai, Yajun,He, Xirui,Bai, Yujun,Sun, Ying,Zhao, Zefeng,Chen, Xufei,Li, Bin,Xie, Jing,Li, Yang,Jia, Pu,Meng, Xue,Zhao, Ye,Ding, Yanrui,Xiao, Chaoni,Wang, Shixiang,Yu, Jie,Liao, Sha,Zhang, Yajun,Zhu, Zhiling,Zhang, Qiang,Zhao, Yuhui,Qin, Fanggang,Zhang, Yi,Wei, Xiaoyang,Zeng, Min,Liang, Jing,Cuan, Ye,Shan, Guangzhi,Fan, Tai-Ping,Wu, Biao,Zheng, Xiaohui
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- Practical Synthesis of Polymethylated Flavones: Nobiletin and Its Desmethyl Derivatives
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We present a practical synthesis of the polymethoxylated citrus flavone nobiletin that is suitable for use on a hundred gram scale. Ready availability of this compound and its derivatives will aid detailed chemical-biological investigations of their biological activities, including activation of signaling via the cAMP-dependent protein kinase A/extracellular signal-related protein kinase/cAMP response element-binding protein pathway.
- Asakawa, Tomohiro,Sagara, Hiroto,Kanakogi, Masaki,Hiza, Aiki,Tsukaguchi, Yuta,Ogawa, Takahiro,Nakayama, Miho,Ouchi, Hitoshi,Inai, Makoto,Kan, Toshiyuki
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p. 595 - 602
(2019/04/01)
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- Synthesis of isoflavones by tandem demethylation and ring-opening/cyclization of methoxybenzoylbenzofurans
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The unexpected conversion of benzoylbenzofurans into isoflavones through an intramolecular cascade that involves deprotection and ring-opening/cyclization is described. This was discovered in an investigation of the possible transformation of benzoylbenzofurans into coumaronochromones. This route affords isoflavones in two major steps from acetophenones and benzoquinones. The transformation was validated by synthesizing differently substituted isoflavone derivatives and further applied to a concise synthesis of a potential anticancer lead compound, glaziovianin A (1).
- Kunyane, Phaladi,Sonopo, Molahlehi S.,Selepe, Mamoalosi A.
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p. 3074 - 3082
(2019/11/19)
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- Studies toward the development of antiproliferative neoclerodanes from salvinorin A
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The success rate for central nervous system (CNS) drug candidates in the clinic is relatively low compared to the industry average across other therapeutic areas. Penetration through the blood-brain barrier (BBB) to reach the therapeutic target is a major obstacle in development. The rapid CNS penetration of salvinorin A has suggested that the neoclerodane nucleus offers an excellent scaffold for developing antiproliferative compounds that enter the CNS. The Liebeskind-Srogl reaction was used as the main carbon-carbon bond-forming step toward the synthesis of quinone-containing salvinorin A analogues. Quinone-containing salvinorin A analogues were shown to have antiproliferative activity against the MCF7 breast cancer cell line, but show no significant activity at the κ-opioid receptors. In an in vitro model of BBB penetration, quinone-containing salvinorin A analogues were shown to passively diffuse across the cell monolayer. The analogues, however, are substrates of P-glycoprotein, and thus further modification of the molecules is needed to reduce the affinity for the efflux transporter.
- Vasiljevik, Tamara,Groer, Chad E.,Lehner, Kurt,Navarro, Hernan,Prisinzano, Thomas E.
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p. 1817 - 1824
(2014/11/07)
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- Exploring the reactivity of nickel complexes in hydrodecyanation reactions
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In the present study, the nickel-catalyzed hydrodecyanation of organic cyanides with lithium borohydride as a cheap hydride source has been examined in detail. As precatalysts straightforward nickel complexes modified by tridentate O,N,O′-ligands and triphenylphosphane as co-ligand have been applied. Noteworthy, excellent yields and chemoselectivities were feasible for a variety of organic cyanides at low catalyst loadings and low temperature (70 C) within short reaction time (3 h).
- Enthaler, Stephan,Weidauer, Maik,Irran, Elisabeth,Epping, Jan Dirk,Kretschmer, Robert,Someya, Chika I.
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p. 262 - 274
(2013/10/01)
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- PET imaging of nobiletin based on a practical total synthesis
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A practical synthesis of nobiletin, a polymethoxylated citrus flavone, was accomplished by utilizing our novel flavone synthesis. Synthetic nobiletin was labelled by selective demethylation and rapid incorporation of 11C atom. Positron emission tomography images successfully visualized the brain distribution, which may provide therapeutic benefits in the treatment of Alzheimer's disease. The Royal Society of Chemistry.
- Asakawa, Tomohiro,Hiza, Aiki,Nakayama, Miho,Inai, Makoto,Oyama, Dai,Koide, Hiroyuki,Shimizu, Kosuke,Wakimoto, Toshiyuki,Harada, Norihiro,Tsukada, Hideo,Oku, Naoto,Kan, Toshiyuki
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p. 2868 - 2870
(2011/04/22)
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- Quinol fatty alcohols as promoters of axonal growth
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The synthesis of three series of quinol fatty alcohols (QFAs) and their biological activities on the promotion of axonal growth are described. Interestingly, the 15-(2,5-dimethoxyphenyl)pentadecan-1-ol, the QFA bearing 15 carbon atoms on the side chain (n = 15), shows the most potent promotion of axonal growth in the presence of both permissive and non-permissive naturally occurring substrates such as Sema3A and myelin proteins.
- Hanbali, Mazen,Vela-Ruiz, Marta,Bagnard, Dominique,Luu, Bang
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p. 2637 - 2640
(2007/10/03)
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- Alternative synthesis of 1,2,3,4-tetramethoxy-5-methylbenzene: A key intermediate for preparing coenzyme Q homologs and analogs
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Preparation of 1,2,3,4-tetramethoxy-5-methylbenzene (1) through a new process from pyrogallol is described. In the preparation, a modified mild brominating agent was employed, and a simple introduction of methyl group into aromatic ring through chloromethylation of the corresponding substrate (4), followed by reductive dehalogenation, was achieved successfully with good yields. Copyright Taylor & Francis Group, LLC.
- Yang, Jian,Weng, Lingling,Zheng, Hu
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p. 2401 - 2405
(2007/10/03)
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- A new fluorogenic transformation: Development of an optical probe for coenzyme Q
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(Chemical Equation Presented) A new fluorogenic transformation based on a quinone reduction/lactonization sequence has been developed and evaluated as a tool for probing redox phenomena in a biochemical context. The probe presented herein is an irreversible redox probe and is reduced selectively by biologically relevant quinols such as ubiquinol but is inert to reduced nicotinamides (e.g., NADH). The ensuing cyclization is fast and quantitative and provides a measurable optical response.
- Tremblay, Matthew S.,Sames, Dalibor
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p. 2417 - 2420
(2007/10/03)
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- Synthesis of 1,2,3,4-tetrahydroxybenzenes from biomass-derived carbon
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A bioengineered synthesis scheme for the production of 1,2,3,4-tetrahydroxybenzene from a carbon source is provided. Methods of producing 1,2,3,4-tetrahydroxybenzene acid from a carbon source based on the synthesis scheme are also provided. Methods are also provided for converting 1,2,3,4-tetrahydroxybenzene to 1,2,3-trihydroxybenzene by catalytic hydrogenation.
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- The synthesis of ventilone A
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2-Amino-3,6-dimethoxy-4,5-methylenedioxybenzoic acid (12) was prepared from 1,4-dimethoxy-2,3-methylenedioxybenzene (8) via the isatin (11). The benzyne generated from (12) was intercepted with 3-acetyl-2-ethoxy-4-[(4-methoxyphenoxy)methyl]furan (4) to give the naphthol (27), which on treatment with ceric ammonium nitrate gave the dimethyl ether of ventilone A (29). Demethylation with boron tribromide then afforded ventilone A (1). CSIRO 2000.
- Piggott, Matthew J.,Wege, Dieter
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p. 749 - 754
(2007/10/03)
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- SYNTHESIS OF HORMOTHAMNIONE
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Hormothamnione 1 has been obtained from 2,3-dimethyl-5,6,7,8-tetramethoxy-chromone 18 in 63percent yield.Synthesis of the required chromone 18 as well as of the 2 and 3-styryl analogs 5 and 9 are described.
- Alonso, Ricardo,Brossi, Arnold
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p. 735 - 738
(2007/10/02)
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- The Structure and Synthesis of Nepenthone-A, a Naphthoquinone from Nepenthes rafflesiana
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The structure of a naphthoquinone, nepenthone-A, isolated from Nepenthes rafflesiana Jack, is shown to be 4,7-dihydroxy-9-methoxy-6-methylnaphto-1,3-dioxole-5,9-dione (6), firs by the synthesis of its di-O-methyl derivative (7), and then by synthesis of the natural product.
- Rizzacasa, Mark A.,Sargent, Melvyn V.
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p. 2017 - 2022
(2007/10/02)
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- XANTHONOLIGNOIDS FROM KIELMEYERA CORIACEA
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Key Word Index - Kielmeyera coriacea; Guttiferae; synthesis; kielcorin; cis-kielcorin; kielcorin B; xanthonolignoids. The synthesis of kielcorin and the tentative identification of kielcorin B (5-hydroxymethyl-6-guaiacyl-2,3:3',2',4'-methoxyxanthone-1,4-dioxane), isomeric xanthonolignoids of Kielmeyera coriacea are reported.
- De M. Pinto, Madalena M.,Mesquita, Antonio A. L.,Gottlieb, Otto R.
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p. 2045 - 2048
(2007/10/02)
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- Syntheses of Agehoustins-A and B
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Agehoustins-A and B formulated as 5,6,7,8,2',3',4',5'-octamethoxyflavone (I) and 5,6,7,2',3',4',5'-heptamethoxyflavone (II) respectively, have been synthesised by the cyclodehydrogenations of the corresponding 2'-hydroxy-3',4',5',6',2,3,4,5-octamethoxychalkone (III) and 2'-hydroxy-4',5',6',2,3,4,5-heptamethoxychalkone (IV).
- Bhardwaj, D. K.,Chand, Gyan,Jain, Anita,Srivastava, Nagesh,Sharma, A. K.
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p. 1163 - 1164
(2007/10/02)
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- SYNTHESIS OF WEBERINE AND NORWEBERINE AND THEIR 1-METHYL CONGENERS
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The synthesis of 2-methyl-5,6,7,8-tetramethoxy-1,2,3,4-tetrahydroisoquinoline (weberine) 5 from 2,3,4,5-tetramethoxy-β-phenylethylamine via norweberine 4 is described.The synthesis of their 1-methyl homologs was also accomplished.
- Takahashi, Kimio,Brossi, Arnold,Diseases, Kidney
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p. 691 - 695
(2007/10/02)
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- SYNTHESIS OF UBIQUINONE AND MENAQUINONE ANALOGUES BY OXIDATIVE DEMETHYLATION OF ALKENYLHYDROQUINONE ETHERS WITH ARGENTIC OXIDE OR CERIC AMMONIUM NITRATE IN THE PRESENCE OF 2,4,6-PYRIDINE-TRICARBOXYLIC ACID
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It was found that alkenylhydroquinone ethers demethylated with argentic oxide or ceric ammonium nitrate in the presence of 2,4,6-pyridinetricarboxylic acid as a catalyst and afforded ubiquinone-2, menaquinone-2 and their analogs in yields of 53 to 89 percent.The new approach to the synthesis of starting alkenylhydroquinone ethers as well as 2,4,6-pyridinetricarboxylic acid and its derivatives has been reported.
- Syper, L.,Kloc, K.,Mlochowski, J.
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p. 123 - 129
(2007/10/02)
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