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

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.

Citation

Yuki Nakatani, Risa Kimura, Tomoyo Kimata, Naoyuki Kotoku, Francisco Sarabia, Ivan Cheng-Sanchez. Oxidative Cyclization at ortho-Position of Phenol: Improved Total Synthesis of 3-(Phenethylamino)demethyl(oxy)aaptamine Marine Drugs. 2023 May 19;21(5)

PMID: 37233505

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