Synthesis of a tetrahydronaphthyridine spiropyrimidinetrione DNA gyrase inhibiting antibacterial agent--differential substitution at all five carbon atoms of pyridine.

The synthesis of (-)-1, a potent antibacterial agent, was achieved stereoselectively in nine steps from readily available starting materials. Directed metalations were developed to assemble a pentasubstituted pyridine with appropriately positioned aldehyde and dimethylmorpholine substituents for a key tertiary amino effect reaction (T-reaction) that led to the spirocylic architecture. Ultimately, (-)-1 was isolated as the thermodynamically most favored stereoisomer.