Enantioselective total synthesis of (-)-colchicine, (+)-demecolcinone and metacolchicine: determination of the absolute configurations of the latter two alkaloids

Here, we describe a concise, enantioselective, and scalable synthesis of (-)-colchicine (9.2% overall yield, >99% ee). Moreover, we have also achieved the first syntheses of (+)-demecolcinone and metacolchicine, and determined their absolute configurations. The challenging tricyclic 6-7-7 core of...

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Bibliographic Details
Published in:Chemical science (Cambridge) 2017-07, Vol.8 (7), p.4961-4966
Main Authors: Chen, Bo, Liu, Xin, Hu, Ya-Jian, Zhang, Dong-Mei, Deng, Lijuan, Lu, Jieyu, Min, Long, Ye, Wen-Cai, Li, Chuang-Chuang
Format: Article
Language:English
Subjects:
Alkaloids
Anticancer properties
Assembly
Biotechnology
Cancer
Cycloaddition
Searching
Synthesis
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Summary:Here, we describe a concise, enantioselective, and scalable synthesis of (-)-colchicine (9.2% overall yield, >99% ee). Moreover, we have also achieved the first syntheses of (+)-demecolcinone and metacolchicine, and determined their absolute configurations. The challenging tricyclic 6-7-7 core of colchicinoids was efficiently introduced using an intramolecular oxidopyrylium-mediated [5 + 2] cycloaddition reaction. Notably, the synthesized colchicinoid exhibited potent inhibitory activity toward the cell growth of human cancer cell lines (IC = ∼3.0 nM), and greater inhibitory activity towards microtubule assembly than colchicine, making it a promising lead in the search for novel anticancer agents.
ISSN:2041-6520
2041-6539
DOI:10.1039/c7sc01341h