Synthesis of New Quinolone Antibiotics Utilizing Azetidine Derivatives Obtained from 1-Azabicyclo[1.1.0]butane

Yoshifumi Ikee; Kana Hashimoto; Mai Kamino; Masaaki Nakashima; Kazuhiko Hayashi; Shigeki Sano; Motoo Shiro; Yoshimitsu Nagao

doi:10.1248/cpb.56.346

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Synthesis of New Quinolone Antibiotics Utilizing Azetidine Derivatives Obtained from 1-Azabicyclo[1.1.0]butane

Yoshifumi Ikee, Kana Hashimoto, Mai Kamino, Masaaki Nakashima, Kazuhiko Hayashi, Shigeki Sano, Motoo Shiro, Yoshimitsu Nagao

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Keywords: azabicyclobutane, azetidine, new quinolone, antibacterial agent, methicillin-resistant Staphylococcus aureus

JOURNAL FREE ACCESS

2008 Volume 56 Issue 3 Pages 346-356

DOI https://doi.org/10.1248/cpb.56.346

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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).

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