63184-61-2Relevant academic research and scientific papers
Synthesis and pharmacological characterisation of arctigenin analogues as antagonists of AMPA and kainate receptors
Butts, Craig P.,Collingridge, Graham L.,Jane, David E.,Mallah, Shahida,Molnár, Elek,Re?nik, Lisa-Maria,Thatcher, Robert J.,Willis, Christine L.
supporting information, p. 9154 - 9162 (2021/11/16)
(-)-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
Conditional Copper-Catalyzed Azide–Alkyne Cycloaddition by Catalyst Encapsulation
Araman, Can,Brevé, Tobias G.,Eelkema, Rienk,Filius, Mike,Hagedoorn, Peter-Leon,Joo, Chirlmin,van Kasteren, Sander I.,van der Helm, Michelle P.
supporting information, p. 9340 - 9344 (2020/04/16)
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.
Rapid stereoselective syntheses of heteroarene-fused azacycles via diastereoselective conjugate addition of heteroaryl substituted lithium amidest
Davies, Stephen G.,Fletcher, Ai M.,Holder, Katherine E.,Roberts, Paul M.,Thomson, James E.,Zimmer, David
, p. 919 - 941 (2019/08/01)
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
ECTONUCLEOTIDASE INHIBITORS AND METHODS OF USE THEREOF
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Page/Page column 100-101, (2020/01/11)
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.
Asymmetric Dearomatization of 1-Aminonaphthalene Derivatives through C-C Bond Formation with Electron-Rich Heterocycles as Nucleophiles
Baba, Takafumi,Oka, Junko,Noguchi, Keiichi,Tanaka, Ken
, p. 4374 - 4382 (2015/07/27)
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.
Total synthesis of the proposed structure of astakolactin
Tonoi, Takayuki,Mameda, Keisuke,Fujishiro, Moe,Yoshinaga, Yutaka,Shiina, Isamu
supporting information, p. 2421 - 2427 (2014/12/12)
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
Synthetic studies towards the core structure of nakadomarin a by a thioamide-based strategy
Chavda, Jai K.,Procopiou, Panayiotis A.,Horton, Peter N.,Coles, Simon J.,Porter, Michael J.
, p. 129 - 139 (2014/01/06)
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.
Semisynthetic neoclerodanes as kappa opioid receptor probes
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.
scheme or table, p. 3100 - 3110 (2012/06/18)
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.
3-formylpyrroles from 3-furfurylamines by bromine oxidation reaction
Harn, Piin-Jye,Lin, Chu-Chung,Wu, Hsien-Jen
scheme or table, p. 1321 - 1326 (2011/10/07)
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
Intramolecular cyclisation of functionalised heteroaryllithiums. Synthesis of novel indolizinone-based compounds
Ruiz, Javier,Lete, Esther,Sotomayor, Nuria
, p. 6182 - 6189 (2007/10/03)
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).
