Nitrogen-containing derivatives of naphthoquinone and podophyllotoxin

Abstract

In the initial, methodological part of this MSc project we intended to expand upon and improve various aspects of the ultrasound accelerated, iodine catalyzed, conjugate addition reaction of amines with 1,4-naphthoquinones first reported by Ji and co-workers in Synthetic Communications (2008, 38, 1201-1211). In recent times, the synthesis of 2-amino-1,4-naphthoquinones has become a heated area of research as a direct consequence of their multitude of diverse pharmaceutical activities; including anticancer, antimalarial, antifungal and trypanocidal properties. Sonochemical transformations, reactions accelerated by ultrasound irradiation, have attracted considerable attention of late due to the shorter reaction durations, higher yields and milder reaction conditions associated with these processes. Additionally, as a result of its unique catalytic properties, iodine has been extensively exploited in diverse, atom-economical and accelerated organic reactions to afford the corresponding products in excellent yields with high selectivity. With these considerations in mind a combinative library of eleven 2-amino-1,4-naphthoquinones with promising anticancer activity were successfully constructed in moderate to exceptional yields, with greatly reduced reaction times, 60 - 90 minutes, using the environmentally friendly, protic solvent ethanol.