Structure and synthesis of antimalarial compound, febrifugine

Malaria is the world's most important tropical parasitic disease and there are an estimated 300-500 million cases of malaria each year. The emergence of multi-drug resistant strains of the parasite is exacerbating the situation. Febrifugine, which was isolated from Dichroa febrifuga and Hydrangea umbellata along with isofebrifugine, is a well-known candidate of antimalarial agent. The plane structure of febrifugine and isofebrifugine was first proposed in 1950. Subsequently, their relative and absolute structures were proposed, based on Baker's synthetic work. The relative configuration of febrifugine was corrected in 1973 and then the absolute structures of febrifugine and isofebrifugine were corrected in 1999. These repeated errors and corrections have caused much confusion in the study of the relationship between the structure and antimalarial activity of febrifugine derivatives. However, investigation of the antimalarial activity of febrifugine derivatives is beginning anew, since it was reported tha t febrifugine had higher activity than clinically used antimalarial drugs, and a derivative potent more than febrifugine was found.