Synthesis of steroidal 1,2- and 1,3-diamines as ligands for transition metal ion complexation

Abstract

Two series of cholestane-based diamines (1,2 and 1,3) were synthesized using simple and efficient procedures. The convenient substrates for these syntheses were cholesteryl mesylate and tosylate, which were converted to appropriate amines via easily obtained azides. The final diamines were prepared using a substitution reaction with bromoacetonitrile (in the case of 1,2-diamines) or condensation with acrylonitrile (in the case of 1,3-diamines), followed by the reduction of intermediate aminonitriles. Furthermore, the other two amines were synthesized from 16-dehydropregnenolone acetate using aza-Michael addition as a key step. Some of the diamines were subjected to complexation reactions with K₂PtCl₄ to form steroidal analogs of cisplatin. The synthetic methods tested in this work will allow us to prepare other cisplatin derivatives based on steroids showing anticancer properties themselves.

Keywords: Aza-Michael addition; Cholesterol; Platinum(II) complexes; Steroidal diamines.