Study On The Synthesis Of Selamectin

Selamectin is a new generation of antiparasitic drug,which was developed by Pfizer and synthesized from doramectin(Microbial fermentation products)by chemical modification.There were multiple routes for synthesis of selamectin using doramectin as raw material.In this thesis,a new synthetic process of selamectin was developed,which was based on the basic patent route.Compared with the patent route,the new process was more suitable for industrial production.Selamectin was prepared from doramectin which involves hydrogenztion,oxidation and oximation-desugar.The first hydrogenation step was performed by replacing acetone with toluene as solvent,which followed milder reaction condition and reduced the hydrogenation of the double bond at C-3,4 position.In the oxidation step,a novel key intermediate was obtained by swern oxidation or Dess-Martin oxidation or Tempo oxidation,The key intermediate was easier to remove the saccharide group in the oximation-desugar process.In the final step,formation of the 5-oxime and hydrolysis of the terminal C-13 saccharide group proceed concurrently and then selamectin was obtained.The effects of each step reaction conditions on the product quality and yield were studied.At the same time,each reaction of the new process was monitored by TLC and the quality of intermediate was examined by HPLC.The above process was an improvement to the basic process patent of Pfizer.Our new process has some advantages of less pollution,high yield,low cost,high efficiency and more suitable for large-scale industrial production.