- Synthesis of new quinolone antibiotics utilizing azetidine derivatives obtained from 1-azabicyclo[1.1.0]butane
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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).
- Ikee, Yoshifumi,Hashimoto, Kana,Kamino, Mai,Nakashima, Masaaki,Hayashi, Kazuhiko,Sano, Shigeki,Shiro, Motoo,Nagao, Yoshimitsu
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p. 346 - 356
(2008/12/22)
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- 4-Hydroxy-quinoline-3-carboxylic
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A process for the preparation of a compound of the formula STR1 in which Y is a nitrile group, an ester group COOR1 or an acid amide CONR2 R3, R1, R2 and R3 each independently is hydrogen or C1 -C4 -alkyl, and R3 may also be phenyl, and X2, X3, X4 and X5 each independently is hydrogen, halogen, nitro, cyano, alkyl having 1-3 carbon atoms, alkoxy having 1-3 carbon atoms, alkylmercapto having 1-3 carbon atoms, alkylsulphonyl having 1-3 carbon atoms, or a phenylsulphonyl group which is optionally substituted in the aryl radical, comprising reacting an aminoacrylate of the formula in which X1 is halogen, a nitro group, an alkoxy, alkoxy, alkylmercapto or alkylsulphonyl group having 1-3 carbon atoms in each case, or an arylsulphonyl group, W is hydrogen or a --CH2 CH2 Z radical, Z is is a nitrile group, an ester group COOR4 or an acid amide group CONR5 R6, and R4, R5 and R6 each independently is hydrogen or C1 -C4 -alkyl, and R5 may also be phenyl, with an acid acceptor in an aprotic solvent. Some of the reactants are new, as are the products which are intermediates for antibacterially active 1-alkyl-4-quinolone-3-carboxylic acids.
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