- Synthesis and characterization of sitafloxacin
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The convenient protocol for the synthesis of sitafloxacin is described. Reaction of ethyl 3-(3-choloro-2,4,5-trifluorophenyl)-3-oxopropanoate with triethylorthoformate and (1R,2S)-(-)-cis-1,2 fluorine cyclopropane amino-p-toluene sulfonic acid salt by condensation under sodium hydrogen condition. The reaction mixture take place hydrolysis of ester in hydrochloric acid solution. Subsequence reacted with (S)-N[(oxoboryl) methylene] -5-azaspiro[2,4]heptan-7-amine by condensation. In the end taken off the protection group gives sitafloxacin and total conversion about 52-65%. The structure of sitafloxacin was characterized by 1H NMR, 13C NMR, IR, MS and elemental analysis.
- Liu, Yu,Liu, Lianxin,Shi, Guangxia
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p. 7049 - 7051
(2015/02/19)
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- (Fluorocyclopropyl)quinolones. 2. Synthesis and stereochemical structure- activity relationships of chiral 7-(7-amino-5-azaspiro[2.4]heptan-5-yl)-1- (2-fluorocyclopropyl)quinolone antibacterial agents
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A series of novel chiral 7-(7-amino-5-azaspiro[2.4]heptan-5-yl)-8-chloro- 1-(2-fluorocyclopropyl)-quinolones were synthesized as a continuation of a research project of 1-(2-fluorocyclopropyl)-quinolones by considering stereochemical and physicochemical properties of the molecule. Absolute configurations of the 1-(cis-2-fluorocyclopropyl) moiety and the 7-(7-amino- 5-azaspiro-[2.4]heptan-5-yl) moiety were determined by X-ray crystallographic analysis. Stereochemical structure-activity relationship studies indicated that 1-[(1R,2S)-2-fluorocyclopropyl] and 7-[(7S)-amino-5-azaspiro[2.4]heptan- 5-yl] derivatives are more potent against Gram-positive and Gram-negative bacteria than the other stereoisomers and 7-[(7S)-7-amino-5-azaspiro[2.4]- heptan-5-yl]-8-chloro-1-[(1R,2S)-2-fluorocyclopropyl]quinolone (33) is the most potent of all stereoisomers. Pharmacokinetic profiles and physicochemical properties of the selected compounds were also examined, and it was found that 33 (DU-6859a) possesses moderate lipophilicity and good pharmacokinetic profiles.
- Kimura,Atarashi,Kawakami,Sato,Hayakawa
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p. 3344 - 3352
(2007/10/02)
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