Organocatalyzed Mannich Reactions on Minocycline: Towards Novel Tetracycline Antibiotics

Herein, we report the development of a mild synthetic route towards novel minocycline derivatives using the proline-catalyzed three-component Mannich reaction. The reaction conditions were optimized and was then screened for its tolerance to the other popular organocatalysts as well as variation of the ketone and aldehyde substrates. The Mannich adducts were evaluated for their in vitro antibacterial efficacies against Gram-negative and Gram-positive bacteria.