The
Ugi-Smiles multicomponent reaction is a powerful tool for obtaining <i>N-</i>arylamines
from acidic phenols and has been widely used for gaining access to structurally
diverse scaffolds. In this work we demonstrate that this isocyanide-based coupling
can be used for the straightforward and efficient synthesis of <i>N,N-</i>disubstituted
3-aminoestrones, steroidal derivatives that usually show interesting biological
activities. In this sense, we analyzed the scope and limitations of the
reaction when applied to aromatic nitrosteroids and found that the outcome is highly influenced by the steric
effects imposed by the steroidal skeleton. After optimization of the reaction
conditions a set of thirteen N-substituted 3-aminoestromes were obtained, some of
them with interesting antiproliferative and antiviral activities.
Recent syntheses of steroidal derivatives containing heterocycles
