Biologically active kavalactones

Both the beverage, kava or yangona, and the dried root of Piper methysticum are used as sources of a series of py-rones with biological activity. Kavalactones in this plant are diuretic, soporific, anticonvulsant, spasmolytic, local anesthetic, and antimycotic (Lebot, 1991). The dried root contains about 5-6% resin from which six related pyrones [yan-gonin (4), desmethoxyyangonin, kawain (5), dihydrokawain, methysticin (6), and dihydromethylsticin] have been isolated. All are more or less potent, centrally acting skeletal muscle relaxants that also possess antipyretic and local anesthetic properties (Tyler et al., 1981). 

Once we realized that the substrate-directed arylation strategy could promote a rapid increase in the structural complexity of the allylic acetates, we decided to apply it in the total synthesis of biologically active kavalactones, represented by compound 18 in Scheme 7. The key step would be the stereoselective arylation of the substrate 19, which would lead us directly to the core skeleton of these natural products. 

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