Diastereoselective synthesis of dispirooxindoles via [3+2] cycloaddition of azomethine ylides to 3-phenacylideneoxindoles and evaluation of their cytotoxicity

被引：30

作者：

Huang, Ying ^{[1
,2
]}

Huang, Yi-Xin ^{[2
]}

Sun, Jing ^{[1
]}

Yan, Chao-Guo ^{[1
]}

机构：

[1] Yangzhou Univ, Coll Chem & Chem Engn, Yangzhou 225002, Jiangsu, Peoples R China

[2] Yangzhou Univ, Coll Med, Yangzhou 225001, Jiangsu, Peoples R China

来源：

RSC ADVANCES | 2018年 / 8卷 / 42期

基金：

中国国家自然科学基金;

关键词：

ONE-POT SYNTHESIS; 1,3-DIPOLAR CYCLOADDITION; 2-OXOINDOLIN-3-YLIDENE DERIVATIVES; SPIROOXINDOLE DERIVATIVES; REGIOSELECTIVE SYNTHESIS; ASYMMETRIC-SYNTHESIS; 2-PI COMPONENTS; GREEN SYNTHESIS; RING-SYSTEMS; FACILE;

D O I：

10.1039/c8ra04375b

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

The three-component reaction of 1,2,3,4-tetrahydroisoquinoline, isatins and 3-phenacylideneoxindoles in refluxing ethanol afforded dispiro[indoline-3,1-pyrrolo[2,1-a]isoquinoline-3,3-indolines] (4a-4x) in good yields via 1,3-dipolar cycloaddition of in situ generated azomethine ylide with the exocyclic double bond of 3-phenacylideneoxindoles. H-1 NMR spectra and single crystal structures indicated the reaction has high regioselectivity and diastereoselectivity. Furthermore, their biological activities have been preliminarily demonstrated by in vitro evaluation against mouse breast cancer cells 4T1 and human liver cancer cells HepG2 by MTT assay. The results demonstrated that some of the compounds showed cytotoxicities to cell lines of 4T1 and HepG2, and indicated that novel spirooxindoles may become potential lead compounds for further biological screenings of their medicinal applications.

引用

页码：23990 / 23995

页数：6

共 53 条

[1] Microwave-mediated Regiospecific Synthesis of Some Novel Annulated Spiro[indoline-3,1'-indolizin]-2-ones [J].

Al-Bogami, Abdullah S. ;

El-Ahl, Abdelaziz S. .

LETTERS IN ORGANIC CHEMISTRY, 2015, 12 (01) :2-12

[2] An expedient approach for the regio- and stereoselective synthesis of novel spiroindolizidines via [3+2] cycloaddition [J].

Alimohammadi, Kamal ;

Sarrafi, Yaghoub ;

Rajabpour, Bahareh .

COMPTES RENDUS CHIMIE, 2014, 17 (02) :156-163

[3] Electrophilicities of 1,2-Disubstituted Ethylenes [J].

Allgaeuer, Dominik S. ;

Mayr, Herbert .

EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, 2014, 2014 (14) :2956-2963

[4] Nucleophilicity Parameters of Pyridinium Ylides and Their Use in Mechanistic Analyses [J].

Allgaeuer, Dominik S. ;

Mayer, Peter ;

Mayr, Herbert .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2013, 135 (40) :15216-15224

[5] A Facile Ionic Liquid Promoted Synthesis, Cholinesterase Inhibitory Activity and Molecular Modeling Study of Novel Highly Functionalized Spiropyrrolidines [J].

Almansour, Abdulrahman I. ;

Kumar, Raju Suresh ;

Arumugam, Natarajan ;

Basiri, Alireza ;

Kia, Yalda ;

Ali, Mohamed Ashraf ;

Farooq, Mehvish ;

Murugaiyah, Vikneswaran .

MOLECULES, 2015, 20 (02) :2296-2309

[6] Novel spirooxindole-pyrrolidine compounds: Synthesis, anticancer and molecular docking studies [J].

Arun, Y. ;

Saranraj, K. ;

Balachandran, C. ;

Perumal, P. T. .

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2014, 74 :50-64

[7] Facile one-pot synthesis of novel dispirooxindole-pyrrolidine derivatives and their antimicrobial and anticancer activity against A549 human lung adenocarcinoma cancer cell line [J].

Arun, Y. ;

Bhaskar, G. ;

Balachandran, C. ;

Ignacimuthu, S. ;

Perumal, P. T. .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2013, 23 (06) :1839-1845

[8] TiO2-silica mediated one pot three component 1,3-dipolar cycloaddition reaction:: a facile and rapid synthesis of dispiroacenaphthenone/oxindole [indanedione/oxindole] pyrroloisoquinoline ring systems [J].

Babu, A. R. Suresh ;

Raghunathan, R. .

TETRAHEDRON, 2007, 63 (33) :8010-8016

[9] Ultrasonic assisted-silica mediated [3+2] cycloaddition of azomethine ylides - a facile multicomponent one-pot synthesis of novel dispiroheterocycles [J].

Babu, A. R. Suresh ;

Raghunathan, R. .

TETRAHEDRON LETTERS, 2007, 48 (38) :6809-6813

[10] Strategies for the enantioselective synthesis of spirooxindoles [J].

Ball-Jones, Nicolas R. ;

Badillo, Joseph J. ;

Franz, Annaliese K. .

ORGANIC & BIOMOLECULAR CHEMISTRY, 2012, 10 (27) :5165-5181

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