Gold-Catalyzed Formal [4+2] Cycloaddition as Access to Antitumor-Active Spirocyclic Oxindoles from Alkynes and Isatin-Derived Ketimines.
Angew Chem Int Ed Engl
; 62(34): e202304672, 2023 Aug 21.
Article
in En
| MEDLINE
| ID: mdl-37204285
ABSTRACT
Due to its excellent bioactivity profile, which is increasingly utilized in pharmaceutical and synthetic chemistry, spirooxindole is an important core scaffold. We herein describe an efficient method for the construction of highly functionalized new spirooxindolocarbamates via a gold-catalyzed cycloaddition reaction of terminal alkynes or ynamides with isatin-derived ketimines. This protocol has a good functional group compatibility, uses readily available starting materials, mild reaction conditions, low catalyst loadings and no additives. It enables the transformation of various functionalized alkyne groups into cyclic carbamates. Gram-scale synthesis was achieved and DFT calculations verify the feasibility of the mechanistic proposal. Some of the target products exhibit good to excellent antiproliferative activity on human tumor cell lines. In addition, one of the most active compounds displayed a remarkable selectivity towards tumor cells over normal ones.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Language:
En
Journal:
Angew Chem Int Ed Engl
Year:
2023
Document type:
Article
Affiliation country:
Germany