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

Organic Chemistry Frontiers Pub Date: 2022-01-05 DOI: 10.1039/D1QO01785C

Abstract

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 α-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.

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