Organocatalytic asymmetric synthesis of multifunctionalized α-carboline-spirooxindole hybrids that suppressed proliferation in colorectal cancer cells

被引：34

作者：

He, Xiang-Hong ^{[1
]}

Fu, Xue-Ju ^{[1
]}

Zhan, Gu ^{[1
]}

Zhang, Nan ^{[1
,2
,3
]}

Li, Xiang ^{[1
]}

Zhu, Hong-Ping ^{[1
,4
]}

Peng, Cheng ^{[1
]}

He, Gu ^{[2
,3
]}

Han, Bo ^{[1
]}

机构：

[1] Chengdu Univ Tradit Chinese Med, Hosp Chengdu Univ Tradit Chinese Med, Sch Pharm, State Key Lab Southwestern Chinese Med Resources, Chengdu 611137, Peoples R China

[2] Sichuan Univ, West China Hosp, State Key Lab Biotherapy, Chengdu 610041, Peoples R China

[3] Sichuan Univ, West China Hosp, Dept Pharm, Chengdu 610041, Peoples R China

[4] Chengdu Univ, Sichuan Ind Inst Antibiot, Antibiot Res & Reevaluat Key Lab Sichuan Prov, Chengdu 610052, Peoples R China

来源：

ORGANIC CHEMISTRY FRONTIERS | 2022年 / 9卷 / 04期

基金：

中国国家自然科学基金;

关键词：

BAYLIS-HILLMAN CARBONATES; CATALYZED 3+3 ANNULATION; ENANTIOSELECTIVE SYNTHESIS; ALLYLIC ALKYLATION; ISATINS; CONSTRUCTION; DERIVATIVES; ADDUCTS; ACCESS;

D O I：

10.1039/D1QO01785C

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

Organocatalytic asymmetric [3 + 3] annulations of isatin-derived MBH carbonates and indolin-2-imines were efficiently achieved. This appears to be the first enantioselective approach for using isatin-derived MBH carbonates as 3C synthons to react with indole-derived C,N-dinucleophiles, yielding a series of multifunctionalized alpha-carboline-spirooxindole hybrids in good to high yields with high stereoselectivities. These synthesized compounds suppressed proliferation in colorectal cancer cell lines. The most potent compound 4h activated autophagy and autophagy flux, and induced cytoprotective autophagy in HCT116 cells. The combination of compound 4h and an autophagy inhibitor could improve their anti-proliferation capacities.

引用

页码：1048 / 1055

页数：8

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