100874-07-5Relevant academic research and scientific papers
Polysubstituted Indole Synthesis via Palladium/Norbornene Cooperative Catalysis of Oxime Esters
Liu, Jiechun,Lin, Haojiang,Jiang, Huanfeng,Huang, Liangbin
supporting information, p. 484 - 489 (2022/01/20)
Polysubstituted indoles are prevalent in pharmaceuticals, agrochemicals, and organic materials. Presented herein is the fact that polyfunctionalized indoles can be efficiently constructed from easily accessible oxime esters and aryl iodides, involving a palladium/norbornene synergistic synthesis. The reaction is enabled by a unique class of electrophiles in palladium/norbornene cooperative catalysis, which are oxime esters derived from simple ketone. The broad substrate scope and high functional group tolerance could make this method attractive for the synthesis of polysubstituted indoles.
Method for synthesizing 2-substituted indole compound from iodobenzene and oxime ester under catalysis of palladium
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Paragraph 0311-0318, (2022/01/05)
The invention belongs to the technical field of organic chemistry, and discloses a method for synthesizing a 2-substituted indole compound from iodobenzene and oxime ester under the catalysis of palladium. The method comprises the following steps of reacting an oxime ester compound with iodobenzene under the action of a palladium catalyst, a phosphine ligand and norbornene by taking an organic solvent as a reaction medium in a protective atmosphere, and carrying out subsequent treatment to obtain the 2-substituted indole compound. According to the method, palladium is used as a catalyst, the phosphine ligand is adopted, the yield is high, and the substrate applicability is wide. In addition, the oxime ester compound is used as a raw material, and the method has the advantages of cheap and easily-prepared raw materials, simple operation, mild reaction conditions and the like.
Indole-3-carbonitriles as DYRK1A inhibitors by fragment-based drug design
Meine, Rosanna,Becker, Walter,Falke, Hannes,Preu, Lutz,Loa?c, Nadège,Meijer, Laurent,Kunick, Conrad
supporting information, (2018/02/07)
Dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) is a potential drug target because of its role in the development of Down syndrome and Alzheimer's disease. The selective DYRK1A inhibitor 10-iodo-11H-indolo[3, 2-c]quinoline-6-carboxy
Formal Total Synthesis of Diazonamide A by Indole Oxidative Rearrangement
David, Nadège,Pasceri, Raffaele,Kitson, Russell R. A.,Pradal, Alexandre,Moody, Christopher J.
, p. 10867 - 10876 (2016/07/27)
A short formal total synthesis of the marine natural product diazonamide A is described. The route is based on indole oxidative rearrangement, and a number of options were investigated involving migration of tyrosine or oxazole fragments upon oxidation of open chain or macrocyclic precursors. The final route proceeds from 7-bromoindole by sequential palladium-catalysed couplings of an oxazole fragment at C-2, followed by a tyrosine fragment at C-3. With the key 2,3-disubstituted indole readily in hand, formation of a macrocyclic lactam set the stage for the crucial oxidative rearrangement to a 3,3-disubstituted oxindole. Notwithstanding the concomitant formation of the unwanted indoxyl isomer, the synthesis successfully delivered, after deprotection, the key oxindole intermediate, thereby completing a formal total synthesis of diazonamide A.
New Indole Tubulin Assembly Inhibitors Cause Stable Arrest of Mitotic Progression, Enhanced Stimulation of Natural Killer Cell Cytotoxic Activity, and Repression of Hedgehog-Dependent Cancer
La Regina, Giuseppe,Bai, Ruoli,Coluccia, Antonio,Famiglini, Valeria,Pelliccia, Sveva,Passacantilli, Sara,Mazzoccoli, Carmela,Ruggieri, Vitalba,Verrico, Annalisa,Miele, Andrea,Monti, Ludovica,Nalli, Marianna,Alfonsi, Romina,Di Marcotullio, Lucia,Gulino, Alberto,Ricci, Biancamaria,Soriani, Alessandra,Santoni, Angela,Caraglia, Michele,Porto, Stefania,Da Pozzo, Eleonora,Martini, Claudia,Brancale, Andrea,Marinelli, Luciana,Novellino, Ettore,Vultaggio, Stefania,Varasi, Mario,Mercurio, Ciro,Bigogno, Chiara,Dondio, Giulio,Hamel, Ernest,Lavia, Patrizia,Silvestri, Romano
, p. 5789 - 5807 (2015/08/24)
We designed 39 new 2-phenylindole derivatives as potential anticancer agents bearing the 3,4,5-trimethoxyphenyl moiety with a sulfur, ketone, or methylene bridging group at position 3 of the indole and with halogen or methoxy substituent(s) at positions 4-7. Compounds 33 and 44 strongly inhibited the growth of the P-glycoprotein-overexpressing multi-drug-resistant cell lines NCI/ADR-RES and Messa/Dx5. At 10 nM, 33 and 44 stimulated the cytotoxic activity of NK cells. At 20-50 nM, 33 and 44 arrested >80% of HeLa cells in the G2/M phase of the cell cycle, with stable arrest of mitotic progression. Cell cycle arrest was followed by cell death. Indoles 33, 44, and 81 showed strong inhibition of the SAG-induced Hedgehog signaling activation in NIH3T3 Shh-Light II cells with IC50 values of 19, 72, and 38 nM, respectively. Compounds of this class potently inhibited tubulin polymerization and cancer cell growth, including stimulation of natural killer cell cytotoxic activity and repression of Hedgehog-dependent cancer.
On the way to biodegradable poly(hydroxy butyrate) from propylene oxide and carbon monoxide via β-butyrolactone: Multisite catalysis with newly designed chiral indole-imino chromium(III) complexes
W?lfle, Heimo,Kopacka, Holger,Wurst, Klaus,Preishuber-Pflügl, Peter,Bildstein, Benno
experimental part, p. 2493 - 2512 (2009/12/01)
Enantioenriched poly(hydroxy butyrate) (PHB) is a biodegradable polyester of significant commercial interest as an environmentally benign substitute of commodity polyolefines. We report on the design and development of new chiral indole-based ligand families and on their chromium(III) complexes as enantioselective catalysts for the conversion of propylene oxide and carbon monoxide to enantioenriched β-butyrolactone, the key monomer for the production of PHB by ring-opening polymerization. The enantioselective carbonylation catalysts are based on new chiral tri- and tetradentate [N2O] and [N4] chromium(III) complexes containing chiral indolaldimine ligand scaffolds. The conceptual design of these ligands is inspired by Jacobsen's salicylaldimine lead structure; the key difference is an exchange of the salicyl-O-donor against an indole-N-donor, allowing additional structural diversity and stereoelectronic tuning by the indole substitution pattern. Synthetically, chiral indolealdimines are easily accessible from 7-formylindoles by standard Schiff base condensation with chiral amine building blocks; the 7-formylindoles in turn are synthesized from the corresponding 7-bromoindoles by the Rapoport synthesis, and the starting 7-bromoindoles are accessible from 2-bromoaniline by the classical Fischer indole synthesis. Three generations of chiral [N2O] and [N4] chromium(III) catalysts have been developed and evaluated in the enantioselective carbonylation of racemic propylene oxide with carbon monoxide using tetracarbonylcobaltate as the nucleophilic reagent for the insertion of carbon monoxide into the activated propylene oxide/chiral Lewis acid complex. The best catalyst out of 10 candidates showed at a temperature of 80 °C an activity of 37% conversion, 100% chemoselectivity, and 19% stereoselectivity.
