Synthesis Of Tilmicosin And Optimization Of The Process Conditions

As a new drug used widely in livestock and poultry breeding, tilmicosin is asemi-synthetic macrolide antibiotic of tylosin. It has several merits： broadantimicrobial spectrum, high security and low drug resistances. This paper introducesthe status of research of tilmicosin; reviews its physicochemical properties, synthesismethod, antimicrobial spectrum and clinical application; introduces and compares itsmethods of testing: UV spectrophotometer, HPLC and1H-NMR; introduces severalpharmaceutical preparations of tilmicosin such as: TMS-TMPL-NE, tilmicosinpellets.Tilmicosin was synthesized as the following method: hydrolysis of tylosinphosphate generated Desmycosin, Desmycosin reacted with3,5-dimethylpiperidine togenerate tilmicosin. The single factor test was used to study the key technologicalparameters of the synthesis experiments, and the best technological parameters werefound out: keeping90min for hydrolysis, pH of hydrolysis is1.6, extracting pH ofDesmycosin is10-11, amount of methanoic is2.0g, reaction time is90min, pHadjusted by HCl is5.0, extracting pH of tilmicosin is10-11. The technologicalconditions of hydrolysis of tylosin phosphate and synthetic reaction of tilmicosinwere studied by orthogonal experiments. The final technological parameters weredetermined: keeping120min for hydrolysis, pH of hydrolysis is1.6, reactiontemperature of hydrolysis is35℃, amount of methanoic is2.0g, reaction time is120min, reaction temperature is70℃. Tilmicosin was synthesized under the bestcondition found out by orthogonal experiments, and its yield is85.51%.Tilmicosin was purified by using its different solubility in water with various pH.After purification, the purity of tilmicosin was increased from82.30%to86.25%.Two methods for determination of the content of tilmicosin(UV and HPLC) werestudied, both the accuracy and the convenience were compared. Tilmicosin wassynthesized by using tylosin tartrate instead of tylosin phosphate, the two methodswere compared from several aspect: appearance, yield, convenience, quality and economy and so on.