- Diversity oriented approach to crownophanes by enyne metathesis and Diels-Alder reaction as key steps
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Various crownophanes are assembled starting with simple phenol derivatives such as catechol, resorcinol, and hydroquinone. Here, cross-enyne metathesis (CEM) and Diels-Alder (DA) reaction have been used as key steps. This strategy has embedded six diversi
- Kotha, Sambasivarao,Waghule, Gopalkrushna T.
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- Probing the Existence of a Metastable Binding Site at the β2-Adrenergic Receptor with Homobivalent Bitopic Ligands
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Herein, we report the development of bitopic ligands aimed at targeting the orthosteric binding site (OBS) and a metastable binding site (MBS) within the same receptor unit. Previous molecular dynamics studies on ligand binding to the β2-adrenergic receptor (β2AR) suggested that ligands pause at transient, less-conserved MBSs. We envisioned that MBSs can be regarded as allosteric binding sites and targeted by homobivalent bitopic ligands linking two identical pharmacophores. Such ligands were designed based on docking of the antagonist (S)-alprenolol into the OBS and an MBS and synthesized. Pharmacological characterization revealed ligands with similar potency and affinity, slightly increased β2/β1AR-selectivity, and/or substantially slower β2AR off-rates compared to (S)-alprenolol. Truncated bitopic ligands suggested the major contribution of the metastable pharmacophore to be a hydrophobic interaction with the β2AR, while the linkers alone decreased the potency of the orthosteric fragment. Altogether, the study underlines the potential of targeting MBSs for improving the pharmacological profiles of ligands.
- Gaiser, Birgit I.,Danielsen, Mia,Marcher-R?rsted, Emil,R?pke J?rgensen, Kira,Wróbel, Tomasz M.,Frykman, Mikael,Johansson, Henrik,Br?uner-Osborne, Hans,Gloriam, David E.,Mathiesen, Jesper Mosolff,Sejer Pedersen, Daniel
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p. 7806 - 7839
(2019/09/07)
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- A study towards the regioselective synthesis of the e,e,e trisadduct of C60 via the [4+2] Diels-Alder reaction with tethers bearing orthoquinodimethane precursors
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The regioselective synthesis of an e,e,e trisadduct of C60 via the Diels-Alder reaction with orthoquinodimethanes has been attempted employing the tether-directed remote functionalization approach. Opened-structure tether 10 and macrocyclic tethers 16 and 21 were synthesized for this purpose. The functionalization of C60 afforded inseparable mixtures of regiomeric trisadducts and the regioselective formation of the e,e,e trisadduct was not feasible even when the more preorganized tethers 16 and 21 were employed. The in situ thermal generation of orthoquinodimethanes from the 1,2-bis(bromomethyl)benzene precursors requires high temperatures and is followed by fast, irreversible cycloaddition with C60 to afford thermally stable products, which prevents the achievement of high regioselectivities.
- Ioannou, Charalambos P.,Chronakis, Nikos
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- Highly efficient synthesis of tetra benzo spiro bis-crown ether
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Novel spiro bis-crown ethers derivatives with four benzo units connected via one carbon bridges have been prepared. These compounds represent well preorganized cavities with interesting complexation abilities towards cations. These macrocyclic were prepared by a four-step via template method by utilizing simple precursors catechol, oliethylen glycol and penta erythritol tetra bromide in good yield. Additionally, cesium carbonate could be used as an excellent base for these reactions.
- Moradgholi, Fatemeh,Vahedi, Hooshang,Lari, Jalil
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- Application of Bayer-Villiger reaction to the synthesis of dibenzo-18-crown-6, dibenzo-21-crown-7 and dihydroxydibenzo-18-crown-6
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Dibenzo-18-crown-6, dibenzo-21-crown-7 and dihydroxy dibenzo-18-crown-6 were synthesized by Bayer-Villiger oxidation strategy. Dibenzo-18-crown-6 and dibenzo-21-crown-7 could be synthesized through a three-step protocol starting from salicylaldehyde. Salicylaldehyde was reacted with bis-(2-chloroethyl)ether using K2CO3 in acetonitrile to link the two phenolic groups with the oxyethylene bridge followed by conversion of the formyl group to the hydroxy group via a Baeyer-Villiger reaction and finally linking the two phenolic group with appropriate oxyethylene bridge. The two target crown ethers were obtained in overall yield, 24% and 30%, respectively. This method has a great potential for synthesis of symmetrical as well as unsymmetrical dibenzo crowns with varying oxyethylene bridges. Baeyer-Villiger oxidation could be used to prepare dihydroxy derivative of dibenzo-18-crown-6 through acetylation of dibenzo-18-crown-6 followed by Baeyer-Villiger oxidation. The Baeyer-Villiger oxidation could be substantially accelerated using trifluoroacetic acid.
- Utekar, Druman R.,Samant, Shriniwas D.
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p. 193 - 197
(2014/05/06)
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- Microwave-assisted synthesis of dibenzo-crown ethers
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Microwave-assisted organic synthesis (MAOS) for dibenzo-substituted crown ethers is presented. Two routes were developed: (1) one-pot MAOS for symmetric dibenzo-crown ethers (DBC) and (2) a two-step MAOS via diphenol intermediates for both symmetric and asymmetric DBCs. MAOS were carried out in open or closed vessels, with or without temperature control at various microwave settings using different bases and reactants. Open vessel MAOS was limited by the volatility of reactants hence was less preferred than the closed vessel MAOS. DBC formation was highly affected by the cation size of the base, which acted as a template ion during DBCs ring closure. Closed vessel MAOS without temperature control was found most appropriate for DBC synthesis. Symmetric DBCs were conveniently obtained via one-pot MAOS whereas asymmetric DBCs were obtained from two-step MAOS via diphenol intermediates. The method was found expedient as it afforded satisfactory yields at considerably shorter reaction time than those in conventional methods.
- Torrejos, Rey Eliseo C.,Nisola, Grace M.,Beltran, Arnel B.,Park, Myoung Jun,Patil, Basavaraj R.,Lee, Seong-Poong,Seo, Jeong Gil,Chung, Wook-Jin
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p. 109 - 115
(2014/03/21)
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- Polybenzocrown ethers: Synthesis by cesium-assisted cyclization and solid-state structures
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A series of large-ring polybenzocrown ethers is prepared by cesium-assisted cyclizations. Reactions of diphenols/bisphenols, dimesylates of oligoethylene glycols and cesium carbonate in MeCN produce the large-ring polybenzocrown ethers in high yields. To gain further insight into the structures of these compounds, solid-state structures of three large-ring crown ethers are obtained by X-ray diffraction.
- Hanes, Robert E.,Ellingsworth, Edward C.,Griffin, Scott T.,Rogers, Robin D.,Bartsch, Richard A.
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p. 217 - 237,21
(2020/08/24)
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- Tribenzo[27]crown-9: A new ring for dibenzylammonium rods
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(formula presented) Dibenzylammonium (DBA+) ions thread through the cavity of tribenzo[27]crown-9 (TB27C9) to generate [2]pseudorotaxanes that are stabilized principally by hydrogen-bonding interactions. The stabilities and complexation kinetic
- Cantrill, Stuart J.,Fyfe, Matthew C. T.,Heiss, Aaron M.,Stoddart, J. Fraser,White, Andrew J. P.,Williams, David J.
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- Radiochemical stability of the dicyclohexano-18-crown-6 ether (DCH18C6): Synthesis and tests in radioactive medium of the DCH18C6 radiolytic products
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The cis-syn-cis isomer of the dicyclohexano-18-crown-6 ether (DCH18C6) was subjected to hydrolysis and radiolysis with a 137Cs gamma source, at different doses of irradiation. The cis-syn-cis DCH18C6 radiolytic products previously identified [1], were synthesized in their different configurations. These radiolytic products, all of cis configuration, were tested on aqueous synthetic solutions of spent nuclear fuels. Experiments in radioactive medium showed that, under continuous extraction conditions, the cis-syn-cis DCH18C6 radiolytic products cannot perturb a reprocessing process using the DCH18C6 as selective extractant. Good prospects for the application of DCH18C6 to spent nuclear fuel reprocessing were therefore demonstrated. An X-ray crystallographic study of the DCH18C6 cis-syn-cis-isomer with uranyl nitrate was investigated. Elsevier,.
- Draye, Micheline,Favre-Reguillon, Alain,Chomel, Rodolph,Faure, Rene,Guy, Alain,Foos, Jacques,Lemaire, Marc
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p. 183 - 197
(2007/10/03)
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- DISUBSTITUTED DIBENZOCROWN ETHERS
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A dibenzocrown ether with 18-membered ring, 2,3,11,12-dibenzo-1,4,7,10,13,16-hexaoxacyclooctadeca-2, 11-diene or dibenzo-18-crown-6, was synthesized through alkylation of catechol with bis (2-chloroethyl) ether, in the presence of a mixture of NaOH and CH3-OH, in n-butanol.This dibenzocrown ether was converted into the diacetyl derivative, which in the presence of sodium hydroxide and bromine gave the dicarboxyl derivative.
- Ardeleanu, Rodinel,Voiculescu, Nicolae,Marcu, Mihai,Calimente, Daniel,Oghina, Radu
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p. 471 - 474
(2007/10/02)
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- Synthesis and Application of Long-Chain Carboxylate Crown-Ether Ionophores for Transport of Metal Cations
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Alkyl-substituted sym-dibenzo-16-crown-5-oxyacetic acid and sym-dibenzo-16-crown-5-oxydodecanic acid were synthesized and applied as ion transport carriers in liquid and film membranes.Increasing crown-ether lipophilicity decreased acid dissociation constants and solubilities of crown-ether carboxylic acids in water but enhanced the solubility and transport ability of the carboxylic anion-K+ complex through a liquid organic (CH2Cl2) membrane.Transport phenomena of the cations alkali-metal ions, alkaline-earth metal ions and transition-metal ions through liquid membranes based on these crown-ether carriers were investigated.Effects of anions, crown-ethers and pH on ion transport are discussed.A mechanism of ion transport through a crown-ether membrane is proposed to include -> and +> in both source and target layers.Ion transport through a polymer/crown-ether film membrane was more efficient than through a liquid membrane. - Key Words: Crown ethers; Ion Transport; Metal Ion; Liquid Membrane; Carrier; Polymer film membrane; Ionophore.
- Jane, Yih-Song,Shih, Jeng-Shong
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p. 719 - 728
(2007/10/03)
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- Calcium ionophores as cardiac stimulants. I. Diacids derived from dibenzo crown ethers
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A series of calcium chelating agents has been prepared based on carboxylic derivatives of open chain 18-Crown-6 analogues. Most of these are efficient calcium binding agents, many form lipophilic calcium complexes, and some of these are capable of releasing Ca2+ from liposomes by ionophore action. The best of these is 1,2-bis-[2-(1-carboxydecyloxy)phenoxy]ethane. This compound is cardiotonic in vitro but in the dog vasoconstriction it is the predominant biological effect.
- Ball,Cooper,Main
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p. 137 - 143
(2007/10/02)
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- Solid-State Inclusion Compounds of New Host Macrocycles with Uncharged Organic Molecules. Host Synthesis, Inclusion Properties, and X-ray Crystal Structure of an Inclusion Compound with 1-Propanol
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A series of organic macrocycles composed of a systematically varied combination of ethano, propano, benzeno, pyridino,and analogous groups, mainly ether-linked (see Chart I), are reported, and their abilities to function as solid-state inclusion hosts are studied.It is found that 3-5, 11-13, 18b, and 21 form crystalline inclusion compounds with a number of low-molecular-weight alcohols such as methanol, ethanol, 1- and 2-propanol, 1-butanol, ethylene glycol, and/or with dimethylformamide and acetonitrile as CH-acidic guests.The observed inclusion selectivities and thestoichiometries of the various host-guest compounds are discussed showing that by and large both chemical and steric host-guest fits apply in the formation of the aggregates.The crystal structure of the inclusion compound of the bipyridino host 11 with 1-propanol (1:1) has been determined from single-crystal X-ray diffraction.There are eight host and guest molecules in each unit cell of dimension a = 2665.2 pm, b = 813.8 pm, c = 2667.4 pm, β = 105.61 deg; space group C2/c; R = 0.088 for 2884 unique reflections.The host macrocycle shows a hollow-type conformation with the 1-propanol molecule coordinated via a moderately stable H-bond to one of the bipyridine nitrogens (O...N = 300 pm).The packing diagram characterizes the host-guest topology largely as a channel-like clathrate (actually "tubulato-coordinatoclathrate").A number of general conclusions that will facilitate the future design of selectively binding hosts for solid-state inclusion are given.
- Weber, Edwin,Josel, Hans-Peter,Puff, Heinrich,Franken, Sybille
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p. 3125 - 3132
(2007/10/02)
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- β1-Selective Adrenoceptor Antagonists. 1. Synthesis and β-Adrenergic Blocking Activity of a Series of Binary (Aryloxy)propanolamines
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A series of binary (aryloxy)propanolamines has been prepared and examined in vitro and in vivo for β-adrenoreceptor blocking activity.These symmetrical compounds consist of two (S)-(phenyloxy)propanolamine pharmacophores coupled through alkylenedioxy or poly(oxyethylenedioxy) linking units of varying lengths.Examples of such binary compounds linked through the 2,2', 3,3', and 4,4' positions in the aromatic rings of the pharmacophores have been prepared.In vitro and in vivo test data indicate that the 2,2' compounds tend to be selective β2-adrenergic blocking agents, the 4,4' binaries tend to be selective β1-blocking agents, and those compounds with 3,3' linkages exhibit intermediate selectivities.One of the 4,4'-linked binary compounds, 4s, exhibited potent, cardioselective β-blockade in vivo, which was of short duration and was accompanied by a prolonged tachycardia.
- Kierstead, R. W.,Faraone, A.,Mennona, F.,Mullin, J.,Guthrie, R. W.,et al.
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p. 1561 - 1569
(2007/10/02)
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- Linewidth Alternation in the Electron Spin Resonance Spectrum of the Fluorene Radical Anion in the Presence of Dibenzo Crown Ethers
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Two dibenzo crown ethers have been found to decompose slowly when in contact with alkali metals in tetrahydrofuran.Decomposition of these dibenzo crown ethers also occurs when they are brought into contact with a solution of the fluorene radical anion.The addition of the crown ethers to a solution of the radical anion has a dramatic effect upon the e.s.r. spectrum.This effect has been interpreted in terms of linewidth alternation.An intramolecular migration of the crown ether-alkali metal cation complex from one side of the radical anion plane to the other is proposed.It has been possible to examine the slow exchange region of the spectrum in the Li(1+)-dibenzo-18-crown-6-fluorene radical anion system.A surprising observation is that these results indicate the complexation of Li(1+) by dibenzo-18-crown-6.
- Rothwell, E. John,Tabner, Brian J.
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p. 1384 - 1391
(2007/10/02)
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- Macrocyclic polyether compounds
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Macrocyclic polyether "crown" compounds of the formula EQU1 WHEREIN T is a C2 -C3 alkylene, A is EQU2 R being H or C1 -C18 alkyl, R2 and R3 being independently C1 -C18 alkyl, C2 -C4 alkenyl, or C6 -C14 aryl; Q and Z are independently 1,2-arylene (or saturated derivatives thereof) or substituted 1,2-arylene (or saturated derivatives thereof); a is 0, 1, 2, or 3; b is an integer from 3 to 20; y is 1 or zero; x1, x2, x3, and x4 are integers independently selected to give a 15-60 atom ring. Such crown compounds are generally useful in the formation of complexes with ionic metal compounds, thus making it possible to use certain chemical reagents in media wherein they are normally insoluble.
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