Sesquiterpene lactones from feverfew, Tanacetum parthenium: isolation, structural revision, activity against human blood platelet function and implications for migraine therapy

Abstract

The structures of two series of sesquiterpene lactones (the ‘α’-series 11, 12 and 16 and the ‘β’-series 15, 17 and 18) present in the herb feverfew have been revised in the light of both X-ray analysis and chemical correlations. A biosynthetic pathway is proposed, involving a Diels–Alder type addition of oxygen followed by two contrasting rearrangements, starting from a common intermediate, the cyclopentadiene 19, which has not been identified in feverfew extracts but which is related to a recently isolated structure. The activity of some of these metabolites as well as of the major sesquiterpene lactone present in feverfew, parthenolide 2, and some simple synthetic models as inhibitors of human blood platelet function has been determined. The possible relevance of this effect to migraine prophylaxis by feverfew is briefly discussed.