The Synthsis Of Linezolid: An Antibiotics Against Resistant Bacteria

Antibiotics are the main drug for clinical infection treatment, the resis-tant bacteria has increased follow the large area use of antibiotics. with therise of bacteria resistance in the world. especially the gram positive bateria(such as MRSA, VRE etc.) bring more difficulty to the clinical treatment.So the study on resistance bacteria and the development of antibiotic resist-ant bacteria has become more and more important.Linezolid was mainly used for the treatment of aerobic gram-positivebacteria infection and it is the first synthetic oxazolidinone antibacterialagents, the new mechanism of linezolid could avoid the cross resistance tothe other antibacterial drugs, so it has a widely applied in clinical practice.This paper compared the synthesis method of linezolid and applied theclassic Buchwald-Hartwig cross-coupling reaction. the chiral oxazolidinonecompounds directly reacted with3-fluoro-4-morpholinyl bromobenzene toobtained the precursor compound and succeed synthetise target compoundlinezolid by the cross-coupling reaction. The five step reactions has impro-ved the synthetic method of linezolid and provides a route which has a lessstep, simple material, feasible operation, at the same time, the five steproute give a way to therapid synthesis of oxazolidinone drugs. In the route of linezolid, we obtained the chiral (R)-5-chloromethyl-2-oxazolidinone from (R)-epichlorohydrin by one step reaction. It reactedwith phthalimide potassium and then coupling with3-fluoro-4-morpholin-ophenyl bromide. Finally completed the synthesis of linezolid via Hydrazi-inolysis reaction and Acetylation reaction.In the synthesis route the material of linezolid. we gave up the diazo-reaction,1,2-difluorobenzene directly reacted with morphine and then obta-ined3-fluoro-4-morpholinophenyl bromide via the bromination reaction.the route have a stabile yield, simple operation, succeed improved theoriginal method which via the diazotized reaction.The structure of compounds are identificated by1H-NMR and13C-NMR.