Pyridine-3,4-dicarboximide as starting material for the total synthesis of the natural product eupolauramine and its isomer iso-eupolauramine endowed with anti-tubercular activities

A direct and convenient synthetic pathway for preparation of the key intermediate aza-isoindolinone 4a/4b, which could be ready obtained from pyridine-3,4-dicarboximide was described. This approach was valorized in the total synthesis of the natural product eupolauramine 7b and in the first synthesis of the position analog iso-eupolauramine 7a, which was obtained after 6 steps in an overall yield of 13%. The developed strategy represents the first synthetic approach employing a starting material already embedding the pyridine and the lactam cycles (cycles D and C, respectively) of the azaphenanthrene lactam framework. These compounds, mainly the new non-natural product, showed a good inhibitory activity against Mycobacterium tuberculosis growth.