Synthesis of N-formylnornuciferine with Cardiotonic Activity

Abstract

(-)-N-Formylnornuciferine (1), an aporphine alkaloid isolated from stems of Tinospora crispa (Borapet in Thai), showed in vitro cardiotonic activity. In an earlier study, it exhibited a significant increase in the force of contraction on the atria of an isolated rat heart with no significant change in the
heart rate. As only very limited amounts of this active compound can be isolated from T. crispa, the evaluation of cardiotonic activity is hampered. One way to obtain sufficient quantities for pharmacological investigation is by chemical synthesis. In the current study, (±)-N-formylnornuciferine (1a) was successfully synthesized in six steps from homoveratrylamine with an overall yield of 50%. A palladiumcatalyzed coupling reaction was the key step in this synthesis. In the subsequent cardiotonic activity test, it was found that the racemic mixture, (±)-N-formylnornuciferine (1a), produced a reduction in the force of contraction and the heart rate, which was different from the activity of the natural aporphine alkoloid isolated from T. crispa.