- New linezolid synthesis method
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The invention belongs to the field of organic synthesis, and particularly relates to a new linezolid synthesis method, which comprises: synthesizing 3-fluoro-4-morpholinophenyl isocyanate by using 3,4-difluoronitrobenzene as a starting raw material, carrying out cyclization on the 3-fluoro-4-morpholinophenyl isocyanate and (R)-epichlorohydrin under the catalysis of MgI2 or MgBr2 in the absence ofa solvent to obtain (R)-3-fluoro-4-morpholinophenyl oxazolidone, and carrying out azide group substitution, reduction and acetylation to obtain linezolid. According to the present invention, by usingthe new linezolid synthesis method, the reaction rate can be significantly accelerated, the yield can be increased, the cost can be reduced, the environment can be protected, the operation is simple,the post-treatment is convenient, and the method is suitable for industrial production.
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- Design and Synthesis of 4-Alkylidene-β-lactams: Benzyl- and Phenethyl-carbamates as Key Fragments to Switch on Antibacterial Activity
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The emergence of multidrug-resistant bacterial strains is particularly important in chronic pathologies such as cystic fibrosis (CF), in which persistent colonization and selection of resistant strains is favored by the frequent and repeated use of antibacterial agents. Staphylococcus aureus is a common pathogen in CF patients that has an associated increased multidrug resistance. In previous studies we demonstrated that the presence of a 4-alkylidene side chain directly linked to a β-lactam appeared to strengthen the potency against S. aureus, especially against methicillin-resistant S. aureus (MRSA) strains. In the present study, 21 new 4-alkylidene-β-lactams were synthesized and evaluated for antibacterial activity. We designed the new compounds to have aryl, benzyl, or phenethyl-carbamate groups on the C3 hydroxyethyl side chain. We found a correlation between biological activity and the nitrogen substituent of the carbamate group, and two phenethyl-carbamate β-lactams were shown to be valuable antibacterial agents against selected linezolid-resistant strains, with a minimum inhibitory concentrations of 2–4 mg L?1.
- Giacomini, Daria,Martelli, Giulia,Piccichè, Miriam,Calaresu, Enrico,Cocuzza, Clementina Elvezia,Musumeci, Rosario
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p. 1525 - 1533
(2017/09/25)
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- A convenient synthesis of the antibacterial agent linezolid
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Starting with 3,4-difluorobenzoic acid (8) and (S)-epichlorohydrin (13) a convergent synthesis of linezolid (1) was developed that is attractive for large scale preparation of the drug. The synthetic strategy involves a 1+3 cycloaddition reaction between the chiral epoxide 11 (prepared from 13) and isocyanate 3 (obtained from 8) that was generated in situ by a Curtius rearrangement. The resulting Schiff base precursor of linezolid (12) crystallized from the reaction mixture and was readily converted to linezolid by an acid-catalyzed hydrolysis followed by an acetylation.
- McCarthy, James R.
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p. 6846 - 6847
(2015/11/27)
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- A facile solvent-free synthesis of chiral oxazolidinone derivatives catalyzed by MgI2 etherate: An approach to enantiopure synthesis of linezolid
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A highly efficient and stereoselective cycloaddition of aryl isocyanates with chiral oxiranes catalyzed by MgI2 etherate under solvent-free conditions was developed to prepare the chiral oxazolidinone derivatives. This methodology has been applied into the practical synthesis of antibacterial drug linezolid.
- Zhang, Xingxian,Zhao, Chengfeng,Gu, Yue
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p. 1143 - 1146,4
(2020/09/16)
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- PROCESSES FOR PREPARING LINEZOLID
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Processes and intermediates for preparing linezolid, and pharmaceutically acceptable salts thereof, are described herein.
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- An efficient and practical synthesis of antibacterial linezolid
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A convergent and efficient synthesis of linezolid was developed using the cycloaddition of commercially available (R)-epichlorohydrin with morpholine substituted phenylisocyanate catalysed by MgI2 or MgBr2 etherate as the key step in the 50% overall yield.
- Zhang, Xingxian,Chen, Wei,Li, Cheng,Wu, Xiang
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experimental part
p. 739 - 740
(2010/03/24)
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- Phthalamide compounds
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The present invention includes a number of novel intermediates such as the (S)-secondary alcohol of formula (VIIIA) X2—CH2—C*H(OH)—CH2—NH—CO—RN??(VIIIA) and processes for production of pharmacologically useful oxazolidinones.
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Page column 11-12
(2010/11/29)
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