1. Enantioselective synthesis of 4-amino-3,4-dihydrocoumarins and their non-cyclic hydroxyester precursors: Biological evaluation for the treatment of glioblastoma multiforme.
- Author
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Borrego, Lorenzo G., Recio, Rocío, Moreno, Nazaret, Chelouan, Ahmed, Álvarez, Eleuterio, Sánchez-Coronilla, Antonio, Caro, Carlos, Pearson, John R., García-Martín, Maria Luisa, Khiar, Noureddine, and Fernández, Inmaculada
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GLIOBLASTOMA multiforme , *HYDROXY esters , *ESTER derivatives , *ETHYL acetate , *ANTINEOPLASTIC agents , *STEREOSELECTIVE reactions - Abstract
The stereoselective addition of ethyl acetate enolate to the C═N bond of N - tert -butylsulfinylimines has been investigated in depth. A significant effect of the LHMDS amount and the N -sulfinylimine nature on the stereoselectivity of the process was observed. Conditions were found where sulfinylimines of differently substituted salicylaldehydes derivatives, ethyl acetate, and LHMDS afforded the corresponding addition products as a single diastereomer in good yields. The developed protocol was successfully applied to the first stereoselective synthesis of differently substituted 4-amino-3,4-dihydrocoumarin derivatives. Computational models confirmed the prominent role of the ortho aryl substituent in the stereoselectivity of the process. A significant and selective cytotoxic activity against Glioblastoma Multiforme (GBM) cancer line has been determined for the noncyclic hydroxy ester derivative. [Display omitted] • The first enantioselective synthesis of 4-amino-3,4-dihydrocoumarins is reported. • The new compounds show selective anticancer activity against GBM cells. • Chiral hydroxy esters derivatives exhibited good performance for the treatment of GBM in vivo. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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