Linezolid Trazodone And Its Analogues Research

Linezolid is a new type of oxazolidinone antibacterial agent with a novel structure and a unique effect mechanism,and without the character of cross drug-resistant.It also has a good antibacterial effect to gram-positive bacterial.Two different methods used in synthesis of linezolid and its analogous.The products were characterized by IR,¹HNMR,¹³C NMR and MS techniques.Bezaldehyde was used as protective agent in first method.S-Epichloeohydrin was aminated and acidulated to give(2S)-1-Amino-3-chloro-propanol Salts.The acetylation of (2S)-1-Amino-3-chloro-propanol by acetic anhydride produced the intermediate (S)-N-[2-(acetyloxy)-3-chloropropyl]acetamide.And then at 20℃,in the presence of lithium tert-butoxide,benzyl 3-fluoro-4-morpholinophenyl carbamate react with(S)-N-[2-(acetyloxy)-3-chloropropyl]acetamide to give linezolid in total yield of 43.6%.The second method dealt with the acylation of(2S)-1-amino-3-chloro-propanol Salts in the presence of triethylamine.And(2S)-1-acetamino-3-chloro-propanol was cyclized by remove of chlorine with sodium tert-butoxide to get S-glycidylacetamid,which reacted with benzyl 3-fluoro-4-morpholinophenylcarbamate to give linezolid.According to the previous documents,this reaction happens in nitrogen gas at-78℃.However we have made some appropriate improvement to avoid the synthesis of oxazolidnone ring at very low temperature. Using dibutyltin dilaurate as catalyst,S-glycidylacetamide reacted with ethyl 3-fluoro-4-morpholonophenylcarbamate at 150-160℃to form linezolid in yield of 65-70%. The mechanism of oxazolidnone ring-forming reaction was also described.In the synthesis of S-glycidylacetamide,we used organic alkali sodium tert-butoxide as dechlorination agent,not only to keep the space frame of the reactant unchanged,but also to obtain successfully the aim product.