Process Research For Transforming α-Artemether Toβ-Artemether Through Epimerization

Malaria is an infectious insect-borne disease. Every year, there are200～500million people infected, and near1million died. In the numerous antimalaria drugs, Coartem is recognized as an important drug that has highly curative effect all over the world. Artemether also has other effects, for example, anti-schistosomiasis, defervescence, anti-inflammation, anticancer. a-Artemether and p-Artememther are two epimers of Artemether, and most used in drugs is β-Artememther. β-Artememther can be synthesized from Artemisinin that derived from Artemisia annua.There are two steps in this process. In the second step that dihydroartemisinin transforming into Artemether, the yield of P-Artememther is60～80%, and10～30%dihydroartemisinin is transformed into a-Artemether. In Artemisia annua,the content of Artemisinin mostly less than1%, so planting should need vast land. If transforming a-Artemether to β-Artememther, the yield of p-Artememther will be increased, the utilization rate of Artemisinin will be raised, and the land for planting can be redused. So it has great social and economic value.At the present time, literature of a-Artemether utilization is few. Two patents refer to a-Artemether utilization, but the yields from a-Artemether to β-Artememther are less than40%and the obtained β-Artememther products are not pure.The aim of this subject is establishing an industrial process to improve the yield of conversion a-Artemether to P-Artememther and obtain high pure β-Artememther.The research of this subject has two parts:reaction research and aftertreatment research.Reaction research uses HPLC method to track the change of material and product.The studied parameters contains catalyzer,solvent, reaction temperature, catalyzer amount,solvent amount,ratio of solvent mixture.The optimized process can raise the conversion rate to above70%. Aftertreatment compares various treat methods to obtain purification process that has high yield and good quality,for example,extraction,distillation,crystallization,etc.Based on the research of reaction and aftertreatment, this thesis establishes an industrial process whose yield is70%and assay is above99%. This thesis solves the problems of low yield and bad quality of conversion a-Artemether to β-Artememther, and creates great social and economic value.