We intend to investigate and develop new, efficient and general synthetic methods for the stereospecific synthesis of vernolepin, vernomenin, encelin and virginin, four sesquiterpenes, three of which possess the alpha-methylene-delta-butyrolactone group. Vernolepin has shown significant anticancer activity in rats, and in general, the alpha-methyl-ene-delta-butyrolactone group appears to be essential for cytotoxic activity among the sesquiterpene lactones. Our approach towards the synthesis of these structurally related natural products follows a convergent synthesis plan, the key step of which involves a new ring annelation reaction. This step will effectively assemble all the structurally important carbon atoms, and a single annelating reagent will be used for the synthesis of all four sesquiterpenes. A heteroatom- initiated fragmentation reaction will be used in order to solve the stereochemical problems inherent in the cis-fused AB ring system present in vernolepin and vernomenin as well as provide the angular vinyl group and functionality necessary for generation of the ring A alpha-methylene- delta-lactone system. The synthesis of encelin and virginin would allow a test of our basic approach to be made on relatively simple models, and furthermore would provide a source of these materials for pharmacological testing. The synthesis of the alpha-methylene lactone group by our proposed methods involving singlet oxygen reaction with endocyclic enol ethers, and reductive elimination of alpha-alkoxy allylic alcohols would be useful in controlling lactone stereochemistry and preparing this functionality from non- carbonyl-containing precursors.