Core Scaffold-Inspired Concise Synthesis of Chiral Spirooxindole-Pyranopyrimidines with Broad-Spectrum Anticancer Potency

被引:107
作者
Jiang, Xianxing [1 ]
Sun, Yulong [1 ]
Yao, Jia [1 ]
Cao, Yiming [1 ]
Kai, Ming [1 ]
He, Ning [1 ]
Zhang, Xiaoyuan [1 ]
Wang, Yiqing [1 ]
Wang, Rui [1 ]
机构
[1] Lanzhou Univ, Key Lab Preclin Study New Drugs Gansu Prov, Inst Biochem & Mol Biol, Cent Lab,Hosp 1, Lanzhou 730000, Peoples R China
基金
中国国家自然科学基金;
关键词
anticancer activity; asymmetric synthesis; pyranopyrimidines; spiroheterocycles; DOUBLY STEREOCONTROLLED APPROACH; ENANTIOSELECTIVE SYNTHESIS; ASYMMETRIC CATALYSIS; MANNICH REACTION; OXINDOLES; CONSTRUCTION; DISCOVERY; EFFICIENT; THIOUREAS; AMINE;
D O I
10.1002/adsc.201100792
中图分类号
O69 [应用化学];
学科分类号
081704 ;
摘要
Due to the lack of tumor-specific anticancer agents, the discovery and development of new types of highly selective anticancer agents is still a very urgent topic. Herein, we present our contribution to concise construction of novel chiral spirooxindole-type pyranopyrimidines exhibiting a unique profile of biological activities. We have found that this new type of spiro alkaloid could inhibit the proliferation of various cancer cells in a preliminary biological evaluation. These findings suggested that spirooxindole-type pyranopyrimidines, developed by an asymmetric Michael/cyclization strategy, can potentially serve as a new kind of anticancer candidate.
引用
收藏
页码:917 / 925
页数:9
相关论文
共 53 条
[1]  
[Anonymous], 2007, ANGEW CHEM, DOI DOI 10.1103/PHYSREVLETT.112.077206
[2]  
Badillo JJ, 2010, CURR OPIN DRUG DISC, V13, P758
[3]   Organocatalytic regio- and asymmetric C-selective SNAr reactions-stereoselective synthesis of optically active spiro-pyrrolidone-3,3′-oxoindoles [J].
Bella, M ;
Kobbelgaard, S ;
Jorgensen, KA .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2005, 127 (11) :3670-3671
[4]  
Bencivenni G., 2009, ANGEW CHEM, V121, P7336
[5]   Targeting Structural and Stereochemical Complexity by Organocascade Catalysis: Construction of Spirocyclic Oxindoles Having Multiple Stereocenters [J].
Bencivenni, Giorgio ;
Wu, Li-Yuan ;
Mazzanti, Andrea ;
Giannichi, Berardino ;
Pesciaioli, Fabio ;
Song, Mao-Ping ;
Bartoli, Giuseppe ;
Melchiorre, Paolo .
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2009, 48 (39) :7200-7203
[6]   Enantioselective Michael/Cyclization Reaction Sequence: Scaffold-Inspired Synthesis of Spirooxindoles with Multiple Stereocenters [J].
Cao, Yiming ;
Jiang, Xianxing ;
Liu, Luping ;
Shen, Fangfang ;
Zhang, Futing ;
Wang, Rui .
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2011, 50 (39) :9124-9127
[7]   Highly Enantioselective Construction of Spiro[4H-pyran-3,3′-oxindoles] Through a Domino Knoevenagel/Michael/Cyclization Sequence Catalyzed by Cupreine [J].
Chen, Wen-Bing ;
Wu, Zhi-Jun ;
Pei, Qing-Lan ;
Cun, Lin-Feng ;
Zhang, Xiao-Mei ;
Yuan, Wei-Cheng .
ORGANIC LETTERS, 2010, 12 (14) :3132-3135
[8]   Organocatalysis mediated by (thio)urea derivatives [J].
Connon, Stephen J. .
CHEMISTRY-A EUROPEAN JOURNAL, 2006, 12 (21) :5418-5427
[9]   A Series of α-Amino Acid Ester Prodrugs of Camptothecin: In Vitro Hydrolysis and A549 Human Lung Carcinoma Cell Cytotoxicity [J].
Deshmukh, Manjeet ;
Chao, Piyun ;
Kutscher, Hilliard L. ;
Gao, Dayuan ;
Sinko, Patrick J. .
JOURNAL OF MEDICINAL CHEMISTRY, 2010, 53 (03) :1038-1047
[10]   Structure-based design of spiro-oxindoles as potent, specific small-molecule inhibitors of the MDM2-p53 interaction [J].
Ding, Ke ;
Lu, Yipin ;
Nikolovska-Coleska, Zaneta ;
Wang, Guoping ;
Qiu, Su ;
Shangary, Sanjeev ;
Gao, Wei ;
Qin, Dongguang ;
Stuckey, Jeanne ;
Krajewski, Krzysztof ;
Roller, Peter P. ;
Wang, Shaomeng .
JOURNAL OF MEDICINAL CHEMISTRY, 2006, 49 (12) :3432-3435