The Synthesis of the Kynurenamines K1 and K2, Metabolites of Melatonin

An efficient synthesis of the kynurenamines K-1 and K-2, the major brain and antioxidant metabolites of melatonin 1 is described. Regioselective lithiation of tert-butyl(4-methoxyphenyl) carbamate and iodination provided the (2-iodoaryl)carbamate which when coupled with N-acetyl-propargylamine underwent a Sonogashira reaction. Simultaneous alkyne hydration and N-formylation produced K-2, whereas alkyne hydration only, produced K-2.