%0 Journal Article
%A Borrego, Lorenzo G
%A Recio, Rocío
%A Moreno, Nazaret
%A Chelouan, Ahmed
%A Álvarez, Eleuterio
%A Sánchez-Coronilla, Antonio
%A Caro, Carlos
%A Pearson, John R
%A García-Martín, Maria Luisa
%A Khiar, Noureddine
%A Fernández, Inmaculada
%T Enantioselective synthesis of 4-amino-3,4-dihydrocoumarins and their non-cyclic hydroxyester precursors: Biological evaluation for the treatment of glioblastoma multiforme.
%D 2022
%U http://hdl.handle.net/10668/22187
%X 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.
%K Enantiopure 4-amino-3,4-dihydrocoumarins
%K Glioblastoma multiforme
%K N-sulfinylarylimines
%K β-hydroxyesters
%~