Studies on the Stereoselective Synthesis of the Marine Antitumor Agent Eleutherobin

(+)-Carvone has been converted into the sulfone 14 which comprises the left-hand side of the cytotoxic sesquiterpene, eleutherobin 1. Julia coupling of 14 to the aldehyde 21, followed by oxidation, dissolving metal reduction and stereoselective reduction of the C8 carbonyl group resulted in 29, which has the correct stereochemistry at C8 and C9. Further conversion of 29 into 37, and attempted intramolecular cyclization resulted in fragmentation to the furan 39 and 38. Asymmetric epoxidation of the allylic alcohols 42 and 48 resulted in neighboring group participation from the adjacent dimethoxy acetal and formation of the rearranged oxepane derivatives 44, 45 and 49, respectively.