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Functionalized 10-Membered Aza- and Oxaenediynes through the Nicholas Reaction

Functionalized 10-Membered Aza- and Oxaenediynes through the Nicholas Reaction

Authors :
Natalia A. Danilkina
Ekaterina A. Khmelevskaya
Anna G. Lyapunova
Alexander S. D’yachenko
Alexander S. Bunev
Rovshan E. Gasanov
Maxim A. Gureev
Irina A. Balova
Source :
Molecules, Vol 27, Iss 18, p 6071 (2022)
Publication Year :
2022
Publisher :
MDPI AG, 2022.

Abstract

The scope and limitations of the Nicholas-type cyclization for the synthesis of 10-membered benzothiophene-fused heterocyclic enediynes with different functionalities were investigated. Although the Nicholas cyclization through oxygen could be carried out in the presence of an ester group, the final oxaenediyne was unstable under storage. Among the N-type Nicholas reactions, cyclization via an arenesulfonamide functional group followed by mild Co-deprotection was found to be the most promising, yielding 10-membered azaendiynes in high overall yields. By contrast, the Nicholas cyclization through the acylated nitrogen atom did not give the desired 10-membered cycle. It resulted in the formation of a pyrroline ring, whereas cyclization via an alkylated amino group resulted in a poor yield of the target 10-membered enediyne. The acylated 4-aminobenzenesulfonamide nucleophilic group was found to be the most convenient for the synthesis of functionalized 10-membered enediynes bearing a clickable function, such as a terminal triple bond. All the synthesized cyclic enediynes exhibited moderate activity against lung carcinoma NCI-H460 cells and had a minimal effect on lung epithelial-like WI-26 VA4 cells and are therefore promising compounds in the search for novel antitumor agents that can be converted into conjugates with tumor-targeting ligands.

Details

Language :
English
ISSN :
14203049
Volume :
27
Issue :
18
Database :
Directory of Open Access Journals
Journal :
Molecules
Publication Type :
Academic Journal
Accession number :
edsdoj.418e404c8d404aa5abefedcc37995ca3
Document Type :
article
Full Text :
https://doi.org/10.3390/molecules27186071