A novel synthesis of tocopheryl amines and amides

We report the synthesis of tocopheryl amines and amides from commercially available tocopherols. This synthesis improves the yield and diastereomeric purity of these biologically important compounds. The tocopheryl amines were prepared from the corresponding alpha- and delta-tocopherols using two distinct synthetic routes. The introduction of the C(6)-amino group can be achieved by aryl nitration/reduction or by Pd-catalyzed Substitution of an aryl triflate, depending on the structure of the starting material. We also prepared the succinamide and maleamide derivatives of each amine. Tocopheryl amides are more potent pro-apoptotic anti-cancer agents than the corresponding alpha-tocopheryl esters. These compounds act selectively within the mitochondria of cancer cells. (C) 2008 Elsevier Ltd. All rights reserved.