3359-49-7Relevant articles and documents
Electrochemical Umpolung C-H Functionalization of Oxindoles
Pastor, Miryam,Vayer, Marie,Weinstabl, Harald,Maulide, Nuno
supporting information, p. 606 - 612 (2022/01/12)
Herein, we present a general electrochemical method to access unsymmetrical 3,3-disubstituted oxindoles by direct C-H functionalization where the oxindole fragment behaves as an electrophile. This Umpolung approach does not rely on stoichiometric oxidants and proceeds under mild, environmentally benign conditions. Importantly, it enables the functionalization of these scaffolds through C-O, and by extension to C-C or even C-N bond formation.
Pharmacophore based drug design and synthesis of oxindole bearing hybrid as anticancer agents
Ali, Abuzer,Devaraji, Vinod,Dewangan, Rikeshwer Prasad,Haider, Kashif,Pandey, Vivek,Pathak, Ankita,Raj Pokharel, Yuba,Saad, Suma,Shahar Yar, M.,Siddiqui, Nadeem
, (2021/09/22)
Dual TK inhibitors have shown significant clinical effects against many tumors, but with unmanageable side effects. Design approach and selectivity of these inhibitors plays substantial role in their potency and side-effects. Understanding the homology of binding sites in targeted receptors, and involvement of signaling proteins after the inhibition might help in producing less toxic but effective inhibitors. Herein, we designed benzylideneindolon-2-one derivatives based on homology modeling in binding sites of VEGFR-2 and EGFR receptors as dual- inhibitor potent anticancer compounds with high selectivity. The benzylideneindolon-2-one derivatives were found to possess conformational switch in form of oxindole, substituted at 2-benzimidazole. Within synthesized compounds, 5b was found most active in in-vitro enzyme inhibition assay against VEGFR-2 and EGFR with highest IC50 value of 6.81 ± 2.55 and 13.04 ± 4.07 nM, respectively. Interestingly, cytotoxicity studies revealed selective toxicity of compound 5b against proliferation of A-431 cell lines (over expressed VEGFR-2 and EGFR) with GI50 value of 0.9 ± 0.66 μM. However, the compounds showed mild to moderate activity in all other cancer cell line in the range of 0.2–100 μM. Further mode of action studies by flow cytometry and western blot on A-431 indicated that they work via apoptosis at S- phase following Bcl/Bax pathway, and cell migration via MMP9. 5b not only suppressed tumor growth but also improved vandetanib associated with weight loss toxicity. Moreover, 5b was found safer than sunitinib and erlotinib with LD50 of 500 mg/kg body weight. These results propose 5b as potential anti-tumor drug with safer profile of conventional inhibitors of VEGFR-2 and EGFR for solid tumors.
Oxidative electro-organic synthesis of dimeric hexahydropyrrolo-[2,3-: B] indole alkaloids involving PCET: Total synthesis of (±)-folicanthine
Bisai, Alakesh,Khatua, Arindam,Paul, Amit,Sharma, Sulekha,Shaw, Kundan
supporting information, p. 9390 - 9395 (2021/11/17)
An efficient electrochemical oxidation strategy for the total synthesis of a dimeric hexahydropyrrolo[2,3-b]indole alkaloid, (±)-folicanthine (1b), has been envisioned. Control experiments suggest that a PCET pathway involving stepwise electron transfer f
Palladium-Catalyzed Allylation of Cyclopropyl Acetylenes with Oxindoles to Construct 1,3-Dienes
Lu, Chuan-Jun,Yu, Xin,Chen, Yu-Ting,Song, Qing-Bao,Yang, Zhen-Ping,Wang, Hong
, p. 680 - 688 (2020/02/11)
A novel palladium-catalyzed allylic alkylation of oxindoles with cyclopropyl acetylenes has been developed. Various 1,3-diene oxindole framework bearing a quaternary stereocenter at the C3 position were synthesized straightforwardly in good to excellent yields with high regio-, and stereoselectivities. The reaction exhibited high atom economy and good functional group tolerance.
Copper(i)/Ganphos catalysis: enantioselective synthesis of diverse spirooxindoles using iminoesters and alkyl substituted methyleneindolinones
Cui, Hao,Duan, Zheng,Li, Er-Qing,Li, Ke,Mathey, Fran?ois,Song, Manman,Wang, Congcong,Wang, Yue,Wei, Donghui
supporting information, p. 3740 - 3746 (2020/06/03)
A copper-catalyzed asymmetric 1,3-dipolar cycloaddition of glycine iminoesters with alkyl substituted 3-methylene-2-oxindoles is described. By usingde novodesign of P-stereogenic phosphines as ligands, spiro[pyrrolidin-3,3'-oxindole]s are generated in good to excellent yields with high asymmetric induction. A further reduced catalyst loading of 0.1 mol% is sufficient to achieve a satisfactory enantioselectivity of 90% ee. The DFT calculations suggest the second Michael addition of the 1,3-dipole to be the rate- andenantio-determining step. A key feature of this 1,3-dipolar cycloaddition is the wide substrate applicability, even with alkyl aldehyde-derived azomethine ylide; thus it has streamlined a highly enantioselective access to a new class of antiproliferative agents, MDM2-p53.
A facile synthesis of novel polycyclic spiropyrrolidine oxindoles incorporating the 1,3-dipolar cycloaddition of azomethine ylides
Treuerne Balázs, Krisztina E.,Molnár, Márk,Madarász, Zoltán,Nyerges, Miklós
supporting information, p. 3245 - 3255 (2020/08/06)
This study describes the synthesis of novel polycyclic spiropyrrolidine oxindoles through the 1,3-dipolar cycloaddition of azomethine ylides generated in situ with 3-(arylmethylene)-indolin-2-ones. Effect of substituents of azomethine ylides and various d
Microfluidic Visible-Light Paternò–Büchi Reaction of Oxindole Enol Ethers
Franceschi, Pietro,Mateos, Javier,Vega-Pe?aloza, Alberto,Dell'Amico, Luca
supporting information, p. 6718 - 6722 (2020/09/11)
A novel microfluidic visible-light process for the functionalisation of oxindoles is reported. The chemistry is based on the reactivity of the corresponding enol ethers, which participate in a site-, regio- and diastereoselective [2+2] heterocycloaddition (Paternò–Büchi) process. The mild reaction conditions, the use of available ketones, together with the high generality (23 examples) and robustness (up to gram scale) make this process a useful synthetic platform for the construction of structurally strained heterocycles.
Asymmetric Synthesis of 3,3′-Piperidinoyl Spirooxindoles and Discovery of Stereospecific Cycloadducts as Novel Hedgehog Pathway Modulators
Flegel, Jana,Heitkamp, Franziska,Kumar, Kamal,Otte, Felix,Pergomet, Jorgelina L.,Rehan, Mohammad,Strohmann, Carsten
supporting information, p. 3140 - 3152 (2020/09/07)
An enantioselective hetero-Diels-Alder reaction of alkylidene oxindoles and 2-aza-3-silyloxy-1,3-butadienes, catalyzed by divalent transition metal complexes with N, N ′-dioxide ligands offered an efficient access to natural-product-based 3,3′-piperidinoyl spirooxindole class of small molecules. exo -Cycloadducts formed via stereospecific cycloaddition with Z -olefin displayed potent activity in modulation of hedgehog pathway.
Activity-directed expansion of a series of antibacterial agents
Chow, Shiao,Clarke, Justin E.,Leggott, Abbie,Nelson, Adam,O'Neill, Alex J.,Warriner, Stuart L.
, p. 8047 - 8050 (2020/08/03)
The feasibility of using activity-directed synthesis to drive antibacterial discovery was investigated. An array of 220 Pd-catalysed microscale reactions was executed, and the crude product mixtures were evaluated for activity against Staphylococcus aureus. Scale-up of the hit reactions, purification and evaluation, enabled expansion of a class of antibacterial quinazolinones. The novel antibacterials had MICs from 0.016 μg mL-1 (i.e. 38 nM) to 2-4 μg mL-1 against S. aureus ATCC29213. This journal is
Photoredox asymmetric catalytic enantioconvergent substitution of 3-chlorooxindoles
Jiang, Zhiyong,Li, Yunqiang,Qiao, Baokun,Zeng, Guangkuo,Zhao, Xiaowei
supporting information, p. 11362 - 11365 (2019/09/30)
An enantioconvergent substitution of 3-substituted 3-chlorooxindoles with N-aryl glycines under visible light irradiation is reported. A transition-metal-free cooperative catalysis platform with a dicyanopyrazine-derived chromophore (DPZ) as a photoredox catalyst and a chiral Br?nsted acid catalyst is effective for these transformations, which involve a single-electron transfer redox step and an enantioselective radical coupling. A variety of valuable chiral 3-aminomethylene-3-substituted oxindoles can be directly synthesized with high yields and enantioselectivities.
