Enantioselective total synthesis of (-)-colchicine, (+)-demecolcinone and metacolchicine: determination of the absolute configurations of the latter two alkaloids.
Chem Sci
; 8(7): 4961-4966, 2017 Jul 01.
Article
in En
| MEDLINE
| ID: mdl-28959419
ABSTRACT
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 23 exhibited potent inhibitory activity toward the cell growth of human cancer cell lines (IC50 = â¼3.0 nM), and greater inhibitory activity towards microtubule assembly than colchicine, making it a promising lead in the search for novel anticancer agents.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Language:
En
Journal:
Chem Sci
Year:
2017
Document type:
Article