Stereoselective total synthesis of (-)-parthenolide

(-)-Parthenolide is a sesquiterpene lactone of the germacranolide class originating from the plant feverfew. It is a promising treatment against endometriosis, a severe and highly diffuse feminine disease which causes chronic symptoms, often incapacitating both physically and psychologically. Moreover, it also shows strong antitumoral properties, similar to those of the chemotherapic 5-azacytidine, and high selectivity towards target tissues. Therefore, the first stereoselective total synthesis of (-)- parthenolide has been approached through a highly selective synthetic pathway, due to its highly interesting pharmacological activity and its shortage in the plant’s extracts. The synthetic route will be characterized by the least number of synthetic steps, as compared to the few already existent semisynthesis6, and stereochemical control will be made possible through the use of 4 key steps. Moreover, by using compound 4 as a common intermediate in two different reactions to obtain intermediate 5 and 3, the synthesis will reconverge by closing on itself giving a “circular synthesis” aimed to reduce resources waste and minimize reactants usage for a greener perspective.