6245-89-2Relevant articles and documents
Synthesis of CF3-Containing Spirocyclic Indolines via a Red-Light-Mediated Trifluoromethylation/Dearomatization Cascade
Gianetti, Thomas L.,Mei, Liangyong,Moutet, Jules,Stull, Savannah M.
, p. 10640 - 10653 (2021/07/31)
A red-light-mediated nPr-DMQA+-catalyzed cascade intramolecular trifluoromethylation and dearomatization of indole derivatives with Umemoto's reagent has been developed. This protocol provides a facile and efficient approach for the construction of functionalized and potentially biologically important CF3-containing 3,3-spirocyclic indolines with moderate to high yields and excellent diastereoselectivities under mild conditions. The success of multiple gram-scale (1 and 10 g) experiments further highlights the robustness and practicality of this protocol and the merit of the employment of red light. Mechanistic studies support the formation of a crucial CF3 radical species and a dearomatized benzyl carbocation intermediate.
Hypoiodite-Catalyzed Chemoselective Tandem Oxidation of Homotryptamines to Peroxy- And Epoxytetrahydropyridoindolenines
Uyanik, Muhammet,Tanaka, Hiroki,Ishihara, Kazuaki
, p. 8049 - 8054 (2020/11/02)
We developed the hypoiodite-catalyzed tandem dearomative peroxycyclization of homotryptamine derivatives to peroxytetrahydropyridoindolenines under mild conditions. During the course of a mechanistic study, we found that a tandem oxidative cyclization/epoxidation as an unexpected reaction proceeded in the presence of TEMPO as an additive. Intramolecular oxidative aminocyclization of homotryptamines at the C-2 position would give tetrahydropyridoindole, a common intermediate for both reactions. Control experiments suggested that while oxidative coupling with TBHP at the C-3 position might afford peroxyindolenines, a preferential electrophilic addition of TEMPO+, which might be generated in situ by the hypoiodite-catalyzed oxidation of TEMPO, at C-3 position followed by elimination and epoxidation might give epoxyindolenines. This serendipitous finding prompted us to develop a chemoselective divergent synthesis of peroxy- and epoxyindolenines by simple modification of the reaction conditions.
Synthesis and Biological Evaluation of Derivatives of Indoline as Highly Potent Antioxidant and Anti-inflammatory Agents
Zeeli, Shani,Weill, Tehilla,Finkin-Groner, Efrat,Bejar, Corina,Melamed, Michal,Furman, Svetlana,Zhenin, Michael,Nudelman, Abraham,Weinstock, Marta
, p. 4004 - 4019 (2018/05/07)
We describe the preparation and evaluation of novel indoline derivatives with potent antioxidant and anti-inflammatory activities for the treatment of pathological conditions associated with chronic inflammation. The indolines are substituted at position 1 with chains carrying amino, ester, amide, or alcohol groups, and some have additional substituents, Cl, MeO, Me, F, HO, or BnO, on the benzo ring. Concentrations of 1 pM to 1 nM of several compounds protected RAW264.7 macrophages against H2O2 induced cytotoxicity and LPS induced elevation of NO, TNF-α, and IL-6. Several derivatives had anti-inflammatory activity at 1/100th of the concentration of unsubstituted indoline. Four compounds with ester, amine, amide, or alcohol side chains injected subcutaneously in mice at a dose of 1 μmol/kg or less, like dexamethasone (5.6 μmol/kg) prevented LPS-induced cytokine elevation in the brain and peripheral tissues. Subcutaneous injection of 100 μmol/kg of these compounds caused no noticeable adverse effects in mice during 3 days of observation.
