SESQUITERPENE LACTONES FROM FEVERFEW, TANACETUM-PARTHENIUM - ISOLATION, STRUCTURAL REVISION, ACTIVITY AGAINST HUMAN BLOOD-PLATELET FUNCTIONAND IMPLICATIONS FOR MIGRAINE THERAPY

The structures of two series of sesquiterpene lactones (the 'alpha'-se ries 11, 12 and 16 and the 'beta'-series 15, 17 and 18) present in the herb feverfew have been revised in the light of both X-ray analysis a nd chemical correlations. A biosynthetic pathway is proposed, involvin g a Diels-Alder type addition of oxygen followed by two contrasting re arrangements, starting from a common intermediate, the cyclopentadiene 19, which has not been identified in feverfew extracts but which is r elated 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 simpler synthetic models as inhibit ors of human blood platelet function has been determined, The possible relevance of this effect to migraine prophylaxis by feverfew is brief ly discussed.