Asymmetric Construction of a Multi-Pharmacophore-Containing Dispirotriheterocyclic Scaffold and Identification of a Human Carboxylesterase 1 Inhibitor

被引：85
作者：
Bao, Xiaoze [1 ]
Wei, Shiqiang [1 ]
Qian, Xingkai [2 ]
Qu, Jingping [1 ]
Wang, Baomin [1 ]
Zou, Liwei [2 ]
Ge, Guangbo [2 ]
机构：
[1] Dalian Univ Technol, Sch Pharmaceut Sci & Technol, State Key Lab Fine Chem, Dalian 116024, Peoples R China
[2] Shanghai Univ Tradit Chinese Med, Inst Interdisciplinary Med, Shanghai 201203, Peoples R China
来源：
ORGANIC LETTERS | 2018年 / 20卷 / 11期
基金：
中国国家自然科学基金;
关键词：
3+3 ANNULATION REACTION; ENANTIOSELECTIVE SYNTHESIS; UNSATURATED PYRAZOLONES; DRUG DISCOVERY; SPIROPYRAZOLONES; SPIROOXINDOLES; CATALYSIS; SEQUENCE; DESIGN; CYCLOADDITION;
D O I：
10.1021/acs.orglett.8b01316
中图分类号：
O62 [有机化学];
学科分类号：
070303 ; 081704 ;
摘要：
A catalytic asymmetric [3 + 2] cyclization of novel 4-isothiocyanato pyrazolones and isatin-derived ketimines was developed, delivering a wide range of intriguing dispirotriheterocyclic products in high yield with excellent diastereoselectivity and enantioselectivity. A chiral sulfoxide derivative of this dispirocyclic product was identified to be a promising hit of the human carboxylesterase 1 inhibitor, and the significant difference of the activity between two enantiomers emphasized the importance of this asymmetric process.
引用
收藏
页码：3394 / 3398
页数：5
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