Oxidative Cyclization at <i>ortho</i>-Position of Phenol: Improved Total Synthesis of 3-(Phenethylamino)demethyl(oxy)aaptamine

Abstract

A shorter synthesis of the demethyl(oxy)aaptamine skeleton was developed via oxidative intramolecular cyclization of 1-(2-azidoethyl)-6-methoxyisoquinolin-7-ol followed by dehydrogenation with a hypervalent iodine reagent. This is the first example of oxidative cyclization at the ortho-position of phenol that does not involve spiro-cyclization, resulting in the improved total synthesis of 3-(phenethylamino)demethyl(oxy)aaptamine, a potent anti-dormant mycobacterial agent.

Keywords

• demethyl(oxy)aaptamine
• total synthesis
• oxidative cyclization
• hypervalent iodine reagent
• anti-mycobacterial agent