ABSTRACT Febrifugine ((+)-1), which was isolated in 1947 from Dichroa febrifuga and Hydrangea umbellata along with isofebrifugine, is a well-known candidate antimalarial agent. Repeated errors and corrections in determining its structure have caused much confusion in the study of the relationship between the structure and antimalarial activity of febrifugine derivatives. Recently, it was reported that (+)-1 had higher activity than antimalarial drugs in clinical use and a derivative more potent than (+)-1 was found. In this review, we describe details of the history and synthesis of (+)-1.
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