Synthesis And Antibacterial Activity Of Oxazolidinone Derivatives

Linezolid,developed by Upjohn Company,went on sale in April 2000, in the United States,which was approved by the FDA.It is used in the treatment of skin and soft tissue infections for the first time as a kind of oxazolidinone derivatives.It has a new antibacterial mechanism:It exerts antimicrobial effects by binding to the 50s subunit of bacterial ribosomes and inhibiting protein sythesisWe synthesized three series of compounds on research of the structure activity relationship of oxazolidinone compounds:(1) 3,4-difluoronitrobenzene as the starting material,after substitution of morpholine, reduction of nitro group, amino protection by benzyl carbonochloridate then reacted with (R)-2-(chloromethyl)oxirane chlorine substituted by sodium acetate, hydrolysis of carboxylic ester, hydroxyl protected by p-toluenesulfonyl chloride.11 compounds were obtained by alcohol, phenol, amine replacement. (2) 1,2-difluoro-4-nitrobenzene as the starting material,hydroxyl substitution,react with intermediate 12, reduction of nitro group, amino protection by benzyl carbonochloridate,then 6 compounds were synthesized by the condensation of intermediate 16. (3) Benzylamine substituting 3,4-difluoronitrobenzene, reduction of nitro group by sodium borohydride, then condensation with intermediate 16, amino dehydration, finally,19 amide compounds were synthesized. Three series of compounds were confirmed by 1HNMR?13C NMR. After evaluating the in vitro anti-microbial activity of the compounds,we found that the antibacterial activity of objective compounds against straphylococcus aureus was not strong,with whose MIC was mostly 32?g/ml,while the MIC of linezolid was 2?g/ml.