- Synthesis and pharmacological characterisation of arctigenin analogues as antagonists of AMPA and kainate receptors
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(-)-Arctigenin and a series of new analogues have been synthesised and then tested for their potential as AMPA and kainate receptor antagonists of human homomeric GluA1 and GluK2 receptors expressed in HEK293 cells using a Ca2+ influx assay. In general, these compounds showed antagonist activity at both receptors with greater activity evident at AMPARs. Schild analysis indicates that a spirocyclic analogue 6c acts as a non-competitive antagonist. Molecular docking studies in which 6c was docked into the X-ray crystal structure of the GluA2 tetramer suggest that (-)-arctigenin and its analogues bind in the transmembrane domain in a similar manner to the known AMPA receptor non-competitive antagonists GYKI53655 and the antiepileptic drug perampanel. The arctigenin derivatives described herein may serve as novel leads for the development of drugs for the treatment of epilepsy. This journal is
- Butts, Craig P.,Collingridge, Graham L.,Jane, David E.,Mallah, Shahida,Molnár, Elek,Re?nik, Lisa-Maria,Thatcher, Robert J.,Willis, Christine L.
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supporting information
p. 9154 - 9162
(2021/11/16)
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- Conditional Copper-Catalyzed Azide–Alkyne Cycloaddition by Catalyst Encapsulation
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Supramolecular encapsulation is known to alter chemical properties of guest molecules. We have applied this strategy of molecular encapsulation to temporally control the catalytic activity of a stable copper(I)–carbene catalyst. Encapsulation of the copper(I)–carbene catalyst by the supramolecular host cucurbit[7]uril (CB[7]) resulted in the complete inactivation of a copper-catalyzed alkyne–azide cycloaddition (CuAAC) reaction. The addition of a chemical signal achieved the near instantaneous activation of the catalyst, by releasing the catalyst from the inhibited CB[7] catalyst complex. To broaden the scope of our on-demand CuAAC reaction, we demonstrated the protein labeling of vinculin with the copper(I)–carbene catalyst, to inhibit its activity by encapsulation with CB[7] and to initiate labeling at any moment by adding a specific signal molecule. Ultimately, this strategy allows for temporal control over copper-catalyzed click chemistry, on small molecules as well as protein targets.
- Araman, Can,Brevé, Tobias G.,Eelkema, Rienk,Filius, Mike,Hagedoorn, Peter-Leon,Joo, Chirlmin,van Kasteren, Sander I.,van der Helm, Michelle P.
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p. 9340 - 9344
(2020/04/16)
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- Rapid stereoselective syntheses of heteroarene-fused azacycles via diastereoselective conjugate addition of heteroaryl substituted lithium amidest
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Conjugate addition of heteroaryl substituted lithium amides to a range of α,β-unsaturated esters followed by in situ enolate oxidation with (-)-(camphorsulfonyl)oxaziridine gave the corresponding α-hydroxy-β-amino esters. Subsequent Friedel-Crafts type cy
- Davies, Stephen G.,Fletcher, Ai M.,Holder, Katherine E.,Roberts, Paul M.,Thomson, James E.,Zimmer, David
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p. 919 - 941
(2019/08/01)
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- ECTONUCLEOTIDASE INHIBITORS AND METHODS OF USE THEREOF
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The invention relates to novel heterocyclic compounds and pharmaceutical preparations thereof. The invention further relates to methods of treating or preventing cancer using the novel heterocyclic compounds of the invention.
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Page/Page column 100-101
(2020/01/11)
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- Asymmetric Dearomatization of 1-Aminonaphthalene Derivatives through C-C Bond Formation with Electron-Rich Heterocycles as Nucleophiles
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A cationic gold(I)/axially chiral biaryl bis(phosphine) complex has been employed to catalyze the asymmetric dearomatization reactions of 1-aminonaphthalene derivatives through a C-C bond-forming reaction with electron-rich heterocycles as the nucleophiles. These reactions afford pentacyclic heterocycles in good yields with moderate enantiomeric excess (ee) values. A cationic gold(I)/axially chiral biaryl bis(phosphine) complex has been employed to catalyze the asymmetric dearomatization of 1-aminonaphthalene derivatives through a C-C bond-forming reaction with electron-rich heterocycles as the nucleophiles. These reactions afford pentacyclic heterocycles in good yields with moderate enantiomeric excess (ee) values.
- Baba, Takafumi,Oka, Junko,Noguchi, Keiichi,Tanaka, Ken
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p. 4374 - 4382
(2015/07/27)
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- Total synthesis of the proposed structure of astakolactin
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The first total synthesis of the proposed structure of astakolactin, a sesterterpene metabolite isolated from the marine sponge Cacospongia scalaris, has been achieved, mainly featuring Johnson-Claisen rearrangement, asymmetric Mukaiyama aldol reaction an
- Tonoi, Takayuki,Mameda, Keisuke,Fujishiro, Moe,Yoshinaga, Yutaka,Shiina, Isamu
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supporting information
p. 2421 - 2427
(2014/12/12)
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- Synthetic studies towards the core structure of nakadomarin a by a thioamide-based strategy
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The tricyclic BCD substructure of the marine natural product nakadomarin A has been synthesised. The strategy utilised a key carbon-carbon bond-forming reaction between a furan and an N-acyliminium ion derived from a secondary thiolactam. In addition, a novel three-component coupling reaction between a thioamide, an allylic bromide and an isocyanate, leading to the establishment of two new stereogenic centres, is reported. Two key steps in a projected total synthesis of nakadomarin A have been realised by using the unique chemistry of thioamides. Formation of the carbocyclic B ring can be effected by nucleophilic attack of a furan on a thiolactam-derived iminium ion, and the key quaternary centre can be established by a novel three-component coupling reaction.
- Chavda, Jai K.,Procopiou, Panayiotis A.,Horton, Peter N.,Coles, Simon J.,Porter, Michael J.
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p. 129 - 139
(2014/01/06)
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- Semisynthetic neoclerodanes as kappa opioid receptor probes
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Modification of the furan ring of salvinorin A (1), the main active component of Salvia divinorum, has resulted in novel neoclerodane diterpenes with opioid receptor affinity and activity. Conversion of the furan ring to an aldehyde at the C-12 position (5) has allowed for the synthesis of analogues with new carbon-carbon bonds at that position. Previous methods for forming these bonds, such as Grignard and Stille conditions, have met with limited success. We report a palladium catalyzed Liebeskind-Srogl cross-coupling reaction of a thioester and a boronic acid that occurs at neutral pH and ambient temperature to produce ketone analogs at C-12. To the best of our knowledge, this is the first reported usage of the Liebeskind-Srogl reaction to diversify a natural product scaffold. We also describe a one-step protocol for the conversion of 1 to 12-epi-1 (3) through microwave irradiation. Previously, this synthetically challenging process has required multiple steps. Additionally, we report in this study that alkene 9 and aromatic analogues 12, 19, 23, 25, and 26 were discovered to retain affinity and selectivity at kappa opioid receptors (KOP). Finally, we report that the furan-2-yl analog of 1 (31) has similar affinity to 1. Collectively, these findings suggest that different aromatic groups appended directly to the decalin core may be well tolerated by KOP receptors, and may generate further ligands with affinity and activity at KOP receptors.
- Lovell, Kimberly M.,Vasiljevik, Tamara,Araya, Juan J.,Lozama, Anthony,Prevatt-Smith, Katherine M.,Day, Victor W.,Dersch, Christina M.,Rothman, Richard B.,Butelman, Eduardo R.,Kreek, Mary Jeanne,Prisinzano, Thomas E.
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p. 3100 - 3110
(2012/06/18)
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- 3-formylpyrroles from 3-furfurylamines by bromine oxidation reaction
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Oxidation of 3-furfurylamines 3a-e with bromine in acetone-water solution gave N-substituted 3-formylpyrroles 4a-e in good yields. A reaction mechanism via the Clauson-Kaas reaction followed by the cis-trans isomerization of the 2-ene-1,4-diones 13 and 14
- Harn, Piin-Jye,Lin, Chu-Chung,Wu, Hsien-Jen
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scheme or table
p. 1321 - 1326
(2011/10/07)
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- Intramolecular cyclisation of functionalised heteroaryllithiums. Synthesis of novel indolizinone-based compounds
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The intramolecular cyclisation of heteroaryllithiums derived from N-heteroarylmethylpyrrole-2-carboxamides takes place smoothly at low temperature when N-methoxy-N-methyl and morpholine amides are used as internal electrophiles. Halogen-lithium exchange using n-BuLi is the method of choice to achieve metalation on the quinoline and pyridine derivatives, while directed lithiation (LDA) works better for furan. In the case of thiophene both methodologies can be applied. These metalation-cyclisation sequences provide a useful entry to several types of indolizidine based compounds (pyrrolo[1,2-b]acridinones, pyrrolo[1,2-g]quinolones, thieno and furo[3,2-f]indolizinones).
- Ruiz, Javier,Lete, Esther,Sotomayor, Nuria
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p. 6182 - 6189
(2007/10/03)
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- Asymmetric Sulfur Ylide Mediated Aziridination: Application in the Synthesis of the Side Chain of Taxol
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(Formula presented). Sulfur ylide methodology has been used to construct the Taxol side chain with a high degree of enantioselectivity via a trans-aziridine followed by stereospecific rearrangement of the trans-benzoylaziridine into a trans-oxazoline.
- Aggarwal, Varinder K.,Vasse, Jean-Luc
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p. 3987 - 3990
(2007/10/03)
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- OXIME ETHER COMPOUND AND AGRICULTURAL OR HORTICULTURAL BACTERICIDE
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An oxime ether compound represented by the formula [I] or a salt thereof which have excellent bactericidal activity and are useful as an agricultural or horticultural fungicide. [I] (In the formula, R1 represents halogeno, hydroxy, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C1-6 alkyl substituted by C1-6 alkoxy, cyano, nitro, C2-6 alkenyl, C2-6 haloalkenyl, C2-6 alkynyl, amino, mono(C1-6 alkyl)amino, di(C1-6 alkyl)amino, C3-6 cycloalkyl, carboxyl, C1-6 alkoxycarbonyl, etc.; R2 represents hydrogen, C1-6 alkyl, C3-6 cycloalkyl, C1-6 haloalkyl, etc.; R3 and R4 each represents hydrogen or C1-6 alkyl; k is an integer of 1 to 4; and A represents the heterocyclic group shown in the description.)
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Page/Page column 42-43
(2010/02/07)
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- Trapping of the putative cationic intermediate in the Morin rearrangement with carbon nucleophiles
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This paper presents reactions in which the putative cationic intermediate in the Morin rearrangement is trapped by aromatic carbon nucleophiles (indoles and furans). For example, reaction of sulfoxide 27 with trifluoroacetic acid in chloroform provides, among other products, indole 29 and indoline 30. The indoline was shown to be in equilibrium with the nine-membered ring bridged indole 31. Other examples of Morin rearrangement-trapping reactions are presented, and mechanisms for these transformations are proposed.
- Freed,Hart,Magomedov
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p. 839 - 852
(2007/10/03)
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- Studies on a potentially prebiotic synthesis of RNA
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Current thinking supports an early phase of evolution in which information transfer and catalysis were mediated by evolving RNA. A novel potentially prebiotic synthesis of RNA is proposed involving polymerisation through aldol condensation followed by a retro-Amadori rearrangement and ring closure via a base-paired mesomeric heterocyclic betaine intermediate. The proposed monomer 1 is an achiral mixed phosphodiester and herein we report synthetic routes to 1 containing each of the four RNA bases, The solution phase behaviour of 1 containing adenine and uracil has been investigated and preliminary results of polymerisation experiments are also presented.
- Sutherland, John D.,Whitfield, J. Nicole
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p. 11595 - 11626
(2007/10/03)
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- Synthetic studies on prehispanolone and 14,15-dihydroprehispanolone
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Employing an intramolecular Michael addition as a pivotal step, butenolide 5, furans 6 and 7 have been converted to dioxaspiro compounds 8, 9, 10 and 11, whose heterocyclic frameworks constitute important structural units of prehispanolone (2) as well as 14,15-dihydroprehispanolones (3) and (4), respectively. Hispanolone (1) was converted to 2, 3 and 4 by utilizing a similar strategy.
- Wang, En Si,Choy, Yuen Min,Wong, Henry N. C.
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p. 12137 - 12158
(2007/10/03)
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- Intramolecular anodic olefin coupling reactions and the use of electron-rich aryl rings
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The utility of intramolecular anodic olefin coupling reactions involving electron-rich aromatic rings for constructing fused, bicyclic ring skeletons has been examined. Reactions involving alkoxy-substituted phenyl rings were found to benefit strongly from a 3-methoxy substituent on the phenyl ring. Although overoxidation of the bicyclic product was observed in these reactions, this problem could be minimized with the use of controlled potential electrolysis conditions when a monomethoxy phenyl ring was used and avoided entirely with the use of a vinyl sulfide moiety as the initiator when a more electron-rich phenyl ring was used. Reactions involving 4-alkoxy-substituted phenyl rings as substrates did not lead to good yields of fused products. Furan rings were found to be excellent coupling partners for the reactions and afforded products having fused, bicyclic furan ring skeletons. Cyclizations involving furans were shown to be compatible with the formation of both six- and seven-membered rings, the generation of a quaternary carbon, and the use of a variety of electron-rich olefins as the other coupling partner. It appears that the furan can serve as either the initiating group or the terminating group for the cyclizations. Finally, the reactions were shown to be compatible with the use of a pyrrole ring as one of the participants.
- New, Dallas G.,Tesfai, Zerom,Moeller, Kevin D.
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p. 1578 - 1598
(2007/10/03)
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- Limonoid model insect antifeedants. A stereoselective synthesis of azadiradione C, D, and E fragments through intramolecular diazo ketone cyclization
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A stereoselective synthesis of model compound 18 of the insect antifeedant azadiradione has been accomplished starting from α-cyclocitral in 12 steps in 15% overall yield. The strategy for the synthesis is based on an intramolecular cyclopropanation of a diazo ketone and subsequent selective cleavage of a cyclopropyl ketone. Reactivity differences in the cleavage of the key cyclopropyl ketone 13 and its homolog 12 lacking the furyl ring are explored.
- Fernandez Mateos,Lopez Barba
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p. 3580 - 3585
(2007/10/02)
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- Model study and partial synthesis of prehispanolone and 14,15-dihydroprehispanolone from hispanolone
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Employing an intramolecular Michael addition as a pivotal step, furan 4 has been converted to dioxaspiro compounds 5 and 6, whose heterocyclic frameworks constitute important structural units of 14,15-dihydroprehispanolone 3 and prehispanolone 1, respectively. Hispanolone 2 was converted to 3 as well as 1 by utilizing a similar strategy.
- Wang, En Si,Luo, Bao Sheng,Mak, Thomas C. W.,Choy, Yuen Min,Wong, Henry N. C.
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p. 7401 - 7404
(2007/10/02)
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- Halogenation of benzyl- and (heteroaromatic methyl)cobaloximes: Direct competition between ring halogenation and cobalt-carbon bond cleavage
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(4-Acetamidobenzyl)- and (4-(dimethylamino)benzyl)cobaloximes react rapidly with low concentrations of chlorine and bromine in acetic acid or chloroform at room temperature under nitrogen. Both ring-halogenated organometallic products and direct Co-C cleavage products are formed. However, (4-methoxybenzyl)cobaloxime forms 4-methoxy-2-halotoluene as the exclusive product. (3-Methylbenzyl)cobaloxime undergoes a substantial proportion of ring substitution by both Br2 and Cl2 in competition with the cleavage of the Co-C bond. (3-Methoxybenzyl)cobaloxime forms only the ring-substituted organometallic product. A remarkable difference in reactivity between 2- and 3-isomers of the (thienylmethyl)- and (furylmethyl)cobaloximes is observed; for example, Co-C cleavage is the primary process in furfuryl- and (2-thienylmethyl)cobaloximes whereas ring halogenation occurs much faster in the 3-isomer. The results are discussed in terms of a σ-π delocalization phenomenon by which the electronic effect of a substituent in the benzyl group is effectively transmitted to the Co-C bond reactivity. The substituent effect of the metallomethyl group -CH2Co(dmgH)2py is found to be more than that of the methoxy group. The mechanism of the Co-C cleavage is described.
- Gupta,Kumar, Manoj,Roy, Sujit
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- A CONVENIENT SYNTHESIS OF PERILLENAL
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A convenient synthesis of chemically and stereoisomerically pure trans-perillenal is described.The compound has been prepared according to a simple procedure from methyl (2E)-5-(3-furyl)-2-methylpent-2-enoate obtained by alkylation of copper dienolate of tiglic or angelic acid with 3-(bromomethyl)furan.
- Bernasconi, Silvana,Colombo, Maristella,Jommi, Giancarlo,Sisti, Massimo
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- REGIO- AND STEREO-SPECIFIC SYNTHESES OF ACHIRAL TERPENOID ALLOMONES AND PHEROMONE COMPONENTS: DENDROLASIN, (E)-β-FARNESENE, AND β-SPRINGENE
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Chemically and stereoisomerically pure dendrolasin (1c), an alarm and defence substance of Lasius fulginosus, has been prepared according to a simple reaction sequence in which the key step involves the reaction of the Grignard reagent derived from 3-(bromomethyl)furan (5) with geranyl acetate (9), in the presence of dilithium tetrachlorocuprate.An analogous reaction has been successfully used to prepare 99percent stereoisomerically pure (Z)-3-(4,8-dimethyl-3,7-nonadienyl)furan (1f) starting from neryl acetate (10).Compound 1c has been also obtained by coupling reaction of 5 with the ?-allylnickel(II) complex derived from geranyl bromide (3).However, in this case 1c was contamined by substantial amounts of 1f.Stereoisomerically pure (E)-β-farnesene (1d), the alarm pheromone of many aphids, has been analogously synthesized by coupling reaction either of the ?-allylnickel halide complex derived from (E)-1-bromo-2-methyl-6-methylene-2,7-octadiene (14) with 1-bromo-3-methyl-2-butene (16), or of ?-(1,1-dimethylallyl)nickel bromide (19) with 14.A similar coupling reaction involving the ?-allylnickel halide derived from 14 and 3 has been employed to prepare β-springene (1e), a diterpene isolated from the dorsal gland of the springbok, Antidorcas marsupialis.
- Carpita, Adriano,Bonaccorsi, Fabrizio,Rossi, Renzo
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p. 443 - 450
(2007/10/02)
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