title: Synthesis of a tetrahydronaphthyridine spiropyrimidinetrione DNA gyrase inhibiting antibacterial agent--differential substitution at all five carbon atoms of pyridine.
abstract: 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.
authors.affiliation: Infection Innovative Medicines, AstraZeneca R&D Boston, 35 Gatehouse Drive, Waltham, Massachusetts 02451, United States.
authors.forename: Gregory S
authors.initials: GS
authors.lastname: Basarab
authors.forename: Vincent
authors.initials: V
authors.lastname: Galullo
authors.forename: Nancy
authors.initials: N
authors.lastname: DeGrace
authors.forename: Sheila
authors.initials: S
authors.lastname: Hauck
authors.forename: Camil
authors.initials: C
authors.lastname: Joubran
authors.forename: Steven S
authors.initials: SS
authors.lastname: Wesolowski
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D003500:Cyclization; D027081:DNA Gyrase / Q000737:chemistry*; D004926:Escherichia coli / Q000737:chemistry*; D015394:Molecular Structure; D009025:Morpholines / Q000737:chemistry*; D009287:Naphthyridines / Q000138:chemical synthesis* / Q000737:chemistry; D011725:Pyridines / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D000900:Anti-Bacterial Agents; D009025:Morpholines; D009287:Naphthyridines; D011725:Pyridines; D027081:DNA Gyrase