title: Synthesis of New Quinolone Antibiotics Utilizing Azetidine Derivatives Obtained from 1-Azabicyclo[1.1.0]butane.
abstract: A series of 3-sulfenylazetidine derivatives 5a-f were synthesized via the ring-opening reactions of 1-azabicyclo[1.1.0]butane (ABB, 3) with thiols 4a-f in 50-92% yields. Treatment of ABB (3) with aromatic amines 9a-e and dibenzylamine (9f) in the presence of Mg(ClO4)2 afforded the corresponding 3-aminoazetidine derivatives 10a-f in 24-65% yields. N-Benzyl-3-bromoazetidine (13), which was obtained by the reaction of ABB (3) with benzyl bromide, gave 3-aliphatic amino-substituted azetidine derivatives 15a, b. Novel fluoroquinolones 7a-f, 11a-f, 16a, b and 25a-c were obtained by the introduction of these azetidine derivatives into the C7 position of a quinolone nucleus 6 and N1-heterocyclic quinolones 21a-c in 21-83% yields. Some of them exhibited a greater antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) in comparison with that of clinically used fluoroquinolone, levofloxacin (LVFX).
authors.affiliation: Graduate School of Pharmaceutical Sciences, The University of Tokushima, Sho-machi, Tokushima 770-8505, Japan.
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Ikee
authors.forename: Kana
authors.initials: K
authors.lastname: Hashimoto
authors.forename: Mai
authors.initials: M
authors.lastname: Kamino
authors.forename: Masaaki
authors.initials: M
authors.lastname: Nakashima
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Hayashi
authors.forename: Shigeki
authors.initials: S
authors.lastname: Sano
authors.forename: Motoo
authors.initials: M
authors.lastname: Shiro
authors.forename: Yoshimitsu
authors.initials: Y
authors.lastname: Nagao
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D053961:Azabicyclo Compounds / Q000737:chemistry*; D001384:Azetidines / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D018360:Crystallography, X-Ray; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D016106:Methicillin Resistance; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D015363:Quinolones / Q000138:chemical synthesis* / Q000494:pharmacology*; D021241:Spectrometry, Mass, Electrospray Ionization; D013211:Staphylococcus aureus / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D053961:Azabicyclo Compounds; D001384:Azetidines; D007202:Indicators and Reagents; D015363:Quinolones; C082735:azetidine