Study On Synthetic Process Of Antimalarial Drug Lumefantrine

Lumefantrine is an antimalarial medicine developed by the Chinese Academy of Military Medical Sciences.Studying the synthetic process and quality standard of lumefantrine is of great significance to reduce the production cost of lumefantrine and improve its quality.On the basis of reviewing the current situation of malaria,several typical antimalarial drugs and several synthetic processes of lumefantrine,this thesis will focus on the synthetic process of lumefantrine.Using industrial fluorene as the main raw material,the crude lumefantrine is prepared by chlorination,Friedel-Crafts acylation,carbonyl reduction,cyclization,epoxy ring opening,condensation.The qualified lumefantrine is obtained by recrystallization in acetone.The process parameters of the reaction were screened and optimized,and the crystallization temperature and solvent of the product were studied in detail.The optimum process conditions of lumefantrine were determined.The total yield of the reaction was 27.6 % and the product content was more than 99%(HPLC).As well,the related substances in the preparation of lumefantrine was investigated and the composition and structure of impurities were determined,respectively.The mechanisms of their formation were discussed,which was favorable to effectively control impurities in the reaction process and improve the quality of products.Finally,on the basis of the small-scale trial process,the project of lumefantrine industrial production was proposed and the corresponding conditions were explored in detail.From the view of reducing the production cost,the process of solvent recovery was explored,which will promote the comprehensive utilization of resources.