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Synthesis of Diverse 6‐Oxa‐allocolchicinoids by a Suzuki–Miyaura Coupling, Acid‐Catalyzed Intramolecular Transacetalization Strategy
Author(s) -
Yadav Dharmendra B.,
Taleli Lebusetsa,
van der Westhuyzen Alet E.,
Fernandes Manuel A.,
Dragoun Maxim,
Prokop Aram,
Schmalz HansGünther,
de Koning Charles B.,
van Otterlo Willem A. L.
Publication year - 2015
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201500573
Subject(s) - chemistry , thiophenol , intramolecular force , stereochemistry , combinatorial chemistry , alkoxy group , organic chemistry , alkyl
The synthesis of allocolchicine analogues is of importance as these compounds have been found to possess promising anticancer activity by affecting tubulin polymerization. In this paper, the synthesis of 28 novel substituted 6‐oxa‐allocolchicinoids is reported. The key steps involved in the synthesis were a Suzuki–Miyaura coupling reaction, followed by an acid‐catalyzed intramolecular transacetalization to afford the desired 5‐alkoxy‐5,7‐dihydrodibenzo[ c , e ]oxepines. In addition, when thiophenol and phenol were used in the transacetalization step, the 5‐(phenylsulfanyl)‐5,7‐dihydrodibenzo[ c , e ]oxepine and 4‐(5,7‐dihydrodibenzo[ c , e ]oxepin‐5‐yl)phenol skeletons were obtained, respectively. The cytotoxicity of the synthetic compounds was unfortunately not impressive; however, one of the compounds was shown to sensitize vincristine‐resistant leukemia and lymphoma cells to vincristine, a result vindicating further synthetic studies.