Synthesis and Activity of a Novel Class of Tribasic Macrocyclic Antibiotics: The Triamilides

The stereoselective synthesis of two novel series of tribasic macrocyclic antibiotics with potent in vitro activity against Pasteurella multocida and Escherichia coli strains of bacteria is described. The in vitro activity can be significantly influenced by the nature of the substituents on the C-4″ aminoalcohol, with the stereochemistry of the C-4″ alcohol playing a less critical role. The effect of substitution and stereochemistry on the in vivo activity in a murine model of respiratory infection is also described. A novel series of tribasic macrocyclic antibiotics with potent in vitro activity against Pasteurella multocida and Escherichia coli strains of bacteria is described.