Iron salt-promoted oxidation of steroidal phenols by m -chloroperbenzoic acid: a route to possible antitumor agents

Abstract

Iron salt-promoted reaction of estrone and its derivatives with meta -chloroperoxybenzoic acid was developed and epoxyquinols were further transformed. Most compounds showed in vitro antiproliferative activity. , A new oxidant, containing m -chloroperoxybenzoic acid (MCPBA) and an iron salt, was developed and used for oxidation of steroidal phenols to a quinol/epoxyquinol mixture. Reaction was optimized for estrone, by varying initiators (Fe-salts), reaction temperature, time and mode of MCPBA application. A series of five more substrates (17β-estradiol and its hydrophobized derivatives) was subjected to the optimized oxidation, providing corresponding p -quinols and 4β,5β-epoxyquinols in good to moderate yields. The obtained epoxyquinols were additionally transformed by oxidation, as well as the acid-catalyzed oxirane opening. In a preliminary study of the antiproliferative activity against human cancer cell lines, all newly synthesized compounds expressed moderate to high activity.