New chiral Mannich adducts of di-tert-butylphenols and a bicyclic imine – Synthesis and antiproliferative activity

• DOI: 10.1016/j.tet.2017.03.017
• Publication Date: 2017-03-09T20:46:38Z
• Authors: Jakub Iwanejko; Elżbieta Wojaczyńska; Justyna Trynda; Magdalena Macieje...; Joanna Wietrzyk; Andrzej Kochel; Jacek Wojaczyński
• Keywords: Imine; Stereocenter; Mannich reaction; Enantiopure drug

Abstract Tests of antiproliferative activity of Mannich adducts of aromatic nucleophiles and a chiral bicyclic imine revealed a di-tert-butylphenol derivative as a promising compound for further exploration. To study the influence of substitution pattern and a configuration of stereogenic centers on the inhibition of cancer cell growth, a series of Mannich bases were obtained with a good to high diastereoselectivity from the reaction of the imine and three isomeric di-tert-butylphenols. Six new enantiopure adducts were isolated and fully characterized. Selected derivatives were shown to exhibit an interesting antiproliferative activity comparable to cisplatin.