31541-32-9Relevant academic research and scientific papers
A general and efficient method to access tetracyclic spirooxindole derivatives
El Bouakher, Abderrahman,Massip, Stphane,Jarry, Christian,Troin, Yves,Abrunhosa-Thomas, Isabelle,Guillaumet, Grald
, p. 556 - 559 (2015)
An efficient, simple, and convenient synthetic procedure for the synthesis of tetracyclic spirooxindole derivatives, starting from N-protected isatins and 2-fluoropyridine, was successfully developed. It enables the facile formation of a new class of spirooxindoles in which the oxindole core is fused with various heterocycles at the C-3 position.
Scope, Limitations and Mechanistic Analysis of the HyperBTM-Catalyzed Acylative Kinetic Resolution of Tertiary Heterocyclic Alcohols**
Smith, Samuel M.,Greenhalgh, Mark D.,Feoktistova, Taisiia,Walden, Daniel M.,Taylor, James E.,Cordes, David B.,Slawin, Alexandra M. Z.,Cheong, Paul Ha-Yeon,Smith, Andrew D.
supporting information, (2021/11/16)
The full scope and limitations of the catalytic acylative kinetic resolution of a range of tertiary heterocyclic alcohols (78 examples, s up to >200) is reported under operationally-simple conditions, using low loadings of a commercially available Lewis basic isothiourea catalyst, HyperBTM (generally 1 mol %). The protocol is highly effective for the kinetic resolution of 3-substituted 3-hydroxyoxindole and α-substituted α-hydroxylactam derivatives bearing up to three potential recognition motifs at the stereogenic tertiary carbinol center. The full power of this methodology has been showcased through the synthesis of highly enantioenriched biologically-active target compounds in both enantiomeric forms. To provide further insight into the reaction mechanism, a detailed kinetic analysis of this Lewis base-catalyzed acylation of tertiary alcohols is reported using the variable time normalization analysis (VTNA) method.
Diastereo- and Enantioselective Synthesis of Borylated 3-Hydroxyoxindoles by Addition of gem-Diborylalkanes to Isatins
Chen, Fen-Er,Li, Hong-Yan,Xiao, You-Cai,Xiong, Tong,Zhou, Li-Yan,Zhou, Yuan
supporting information, p. 791 - 796 (2022/01/28)
The catalytic asymmetric synthesis of borylated 3-hydroxyoxindoles by addition of gem-diborylalkanes to isatins is disclosed. Chiral 3-hydroxyoxindoles bearing two contiguous stereogenic centers were produced in up to >20:1 dr and 99% ee. The synthetic utility of the corresponding products is presented through several transformations of the boryl moiety. This report provides an efficient strategy to incorporate a boryl functional group toward the synthesis of 3-hydroxyoxindoles.
Synthesis and biological evaluation of isatin derivatives containing 1,3,4-thiadiazole as potent a-glucosidase inhibitors
Zhao, Xuelian,Zhan, Xuehui,Zhang, Huilin,Wan, Yichao,Yang, Huizhong,Wang, Yutian,Chen, Yanda,Xie, Wenlin
supporting information, (2021/11/16)
A series of (Z)-3-(2-(1,3,4-thiadiazol-2-yl)hydrazono)-1-substituted indolin-2-ones derivatives (3a-3m) were designed and synthesized. All newly synthesized compounds were evaluated for their a-glucosidase inhibitory activity with resveratrol as positive control in vitro. Except for 3i and 3j, all of the compounds showed a potent inhibitory activity against a-glucosidase with IC50 values in the range of 3.12 ± 1.25 to 45.95 ± 1.26 μM and the purity of these compounds was greater than 95%. The IC50 values were being compared to the standard resveratrol (IC50 = 22.00 ± 1.15 μM) and it was found that compounds 3b, 3d-3h were found to be more active than resveratrol. Specifically, (Z)-3-(2-(1,3,4-thiadiazol-2-yl)hydrazono)-1-(4-chlorobenzyl)indolin-2-one (3d) exhibited the most potent a-glucosidase inhibitory activity with IC50 value of 3.12 ± 1.25 μM. The kinetic analysis revealed that compound (3d) is noncompetitive inhibitor. Structure activity relationship has been established for all compounds. Furthermore, the binding interactions of compound 3d with the active site of a-glucosidase were confirmed through molecular docking. This study has identified a new class of potent a-glucosidase inhibitors for further investigation.
Palladium-Catalyzed Cascade Hydrosilylation and Amino-Methylation of Isatin Derivatives
Liu, Yue,Xia, Yun-Tao,Cui, Su-Hang,Ji, Yi-Gang,Wu, Lei
supporting information, p. 2632 - 2636 (2020/06/02)
We demonstrate that using palladium acetate as a catalyst for reduction of DMF and isatin derivatives by hydrosilanes, a cascade hydrosilylation and amino-methylation reaction can be realized. With DMF as a reactant and a solvent, the in-situ generated siloxymethylamine intermediate, an adduct of DMF and hydrosilanes, smoothly participates in the successive stages, providing a serials of Si, N-functionalized indolin-2-ones in moderate to good yields. This strategy exhibits high chemoselectivity toward carbonyl moieties reduction among the substrates. (Figure presented.).
Acylation of oxindoles using methyl/phenyl estersviathe mixed Claisen condensation - an access to 3-alkylideneoxindoles
Gandhi, Thirumanavelan,Nagaraja, C. M.,Panyam, Pradeep Kumar Reddy,Rajeshwaran, Purushothaman,Sreedharan, Ramdas,Yadav, Saurabh
supporting information, p. 3843 - 3847 (2020/06/03)
Predominantly, aggressive acid chlorides and stoichiometric coupling reagents are employed in the acylating process for synthesizing carbonyl tethered heterocycles. Herein, we report simple acyl sources,viz. methyl and phenyl esters, which acylate oxindolesviathe mixed Claisen condensation. This straightforward protocol is mediated by LiHMDS and KOtBu and successfully applied to a wide range of substrates. It is a noteworthy transformation that skips the stepwise generation of enolates and acylation, and the reaction is performed at a moderate temperature with no side reactions. This protocol produces the first examples ofortho-substituents in an aryl ring flanked with electron-donating and electron-withdrawing substrates. Interestingly, robust organometallic ferrocenyl methyl ester cleaved under these conditions with ease. Furthermore, biologically important Tenidap's analog was synthesized by this protocol.
Novel Multitarget Directed Triazinoindole Derivatives as Anti-Alzheimer Agents
Patel, Dushyant V.,Patel, Nirav R.,Kanhed, Ashish M.,Patel, Sagar P.,Sinha, Anshuman,Kansara, Deep D.,Mecwan, Annie R.,Patel, Sarvangee B.,Upadhyay, Pragnesh N.,Patel, Kishan B.,Shah, Dharti B.,Prajapati, Navnit K.,Murumkar, Prashant R.,Patel, Kirti V.,Yadav, Mange Ram
, p. 3635 - 3661 (2019/08/20)
The multifaceted nature of Alzheimer's disease (AD) demands treatment with multitarget-directed ligands (MTDLs) to confront the key pathological aberrations. A novel series of triazinoindole derivatives were designed and synthesized. In vitro studies revealed that all the compounds showed moderate to good anticholinesterase activity; the most active compound 23e showed an IC50 value of 0.56 ± 0.02 μM for AChE and an IC50 value of 1.17 ± 0.09 μM for BuChE. These derivatives are also endowed with potent antioxidant activity. To understand the plausible binding mode of the compound 23e, molecular docking studies and molecular dynamics simulation studies were performed, and the results indicated significant interactions of 23e within the active sites of AChE as well as BuChE. Compound 23e successfully diminished H2O2-induced oxidative stress in SH-SY5Y cells and displayed excellent neuroprotective activity against H2O2 as well as Aβ-induced toxicity in SH-SY5Y cells in a concentration dependent manner. Furthermore, it did not show any significant toxicity in neuronal SH-SY5Y cells in the cytotoxicity assay. Compound 23e did not show any acute toxicity in rats at doses up to 2000 mg/kg, and it significantly reversed scopolamine-induced memory deficit in mice model. Additionally, compound 23e showed notable in silico ADMET properties. Taken collectively, these findings project compound 23e as a potential balanced MTDL in the evolution process of novel anti-AD drugs.
Synthesis and biological evaluation of polyhydroxylated oxindole derivatives as potential antileishmanial agent
Yousuf, Md,Mukherjee, Debarati,Dey, Somaditya,Chatterjee, Saurav,Pal, Abhishek,Sarkar, Biswajyoti,Pal, Chiranjib,Adhikari, Susanta
supporting information, p. 1056 - 1062 (2018/02/27)
The devastating appearance of numerous drug-unresponsive strains of Leishmania donovani and severe toxic side effects of conventional antileishmanial therapy necessitates the search for novel leads, to treat visceral leishmaniasis efficiently. The current study deals with the synthesis and biological evaluation of a unique C-5 functionalized oxindole based polyphenol to ascertain its activities against L. donovani infection, in vitro. The polyhydroxylated oxindole derivative (1) was generated by coupling styrene derivatives with 5-bromo bis-arylidene oxindole using Heck coupling reaction. The synthesized molecule 1 was tested for its antileishmanial activity using both promastigote and amastigote stages of L. donovani. Molecule 1 showed promising anti-promastigote and anti-amastigote activities with IC50 values 15 μM and 1 μM, respectively, with no cytotoxicity towards host splenocytes. The results revealed that this compound induced parasite death by promoting oxidative stress, thereby triggering apoptosis.
Development of Novel Chloramphenicol Scaffold-Based Chiral Hydroxyl Oxazoline Ligands and Their Application to the Asymmetric Alkynylation of Isatins
Chen, Lei,Huang, Guanxin,Liu, Minjie,Huang, Zedu,Chen, Fen-Er
supporting information, p. 3497 - 3501 (2018/09/14)
The synthesis of new chloramphenicol base-derived chiral hydroxyl oxazoline ligands, and their use in the first Zn(OTf)2-catalyzed enantioselective alkynylation of isatins are described. This transformation features mild reaction conditions, a remarkably broad substrate scope, and excellent functional group tolerance, affording the corresponding tertiary propargylic alcohols in high yields and with high enantioselectivities. The application of chiral hydroxyl oxazolines as ligands in Zn(II)-catalyzed asymmetric alkynylation reactions is unprecedented. (Figure presented.).
Reactivity of spiroanthraceneoxazolidines with cyclopropanes: An approach to the oxindole alkaloid scaffold
Buev, Evgeny M.,Moshkin, Vladimir S.,Sosnovskikh, Vyacheslav Y.
supporting information, p. 3409 - 3412 (2018/08/20)
The reaction of N-methylspiro[anthracene-oxazolidine] with spiro[cyclopropane-3,3′-indolin]-2-ones in the presence of MgI2 formed the corresponding spiro[pyrrolidine-3,3′-indolin]-2-ones in 42–65% yields. The use of N-benzylspiro[anthracene-oxazolidine] in this reaction led to the formation of a mixture of the corresponding N-methyl- and N-benzylpyrrolidines.
