An effective and straight forward method for the synthesis of 1-aminoanthracene-9,10-dione carboxamides, by coupling weakly reactive amine, 1-aminoanthracene-9,10-dione, and sterically hindered carboxylic acids was achieved using COMU as the coupling agent. Further, making use of advantages associated with the super-critical fluid chromatography (SFC) technique, a simplified and straight forward method, for chiral separation of optically active amide derivatives, from the impurities associated with the reaction mixture, in a single step, was demonstrated. The anti-microbial activity of selected 1-aminoanthracene-9,10-dione carboxamides was studied. Advanced NMR and other spectral techniques were used for the thorough characterization of all the compounds. This study, provides a general and simplified method for coupling a weak amine with sterically hindered acid using COMU as a coupling agent, separation of optically pure compounds from reaction related impurities in a single step using SFC, and identifies amide derivatives of 1-aminoanthracene-9,10-dione as potential anti-microbial agents.