Design and Synthesis of a Novel Alpha-Methylene Lactone Chemotherapeutic Agent

Goniothalamin, a natural product isolated from the dried stem bark of Malaysian plants of the genus Goniothalamus, has been shown to induce apoptosis in cancer cells. The bioactivity of this molecule is though to be due to its ability to react with thiols. One mechanism involves its reaction with glutathione, a natural antioxidant found in all cells. Using a four step synthetic sequence, a novel gamma-lactone analogue of goniothalamin has been prepared that replaces the endocylic double bond in goniothalamin\u27s lactone core with an exocyclic double bond. It is anticipated that this alteration will allow the compound to react more rapidly with thiols and therefore increase its cytotoxicity towards cancer cells