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 o f 14 to the aldehyde 21, followed by oxidation, dissolving metal reduction and stereoselective reduction of the C8 carbonyl group resulted in 29, whic h has the correct stereochemistry at C8 and C9. Further conversion of 29 in to 37, and attempted intramolecular cyclization resulted in fragmentation t o the furan 39 and 38. Asymmetric epoxidation of the allylic alcohols 42 an d 48 resulted in neighboring group participation from the adjacent dimethox y acetal surd formation of the rearranged oxepane derivatives 44, 45 and 49 , respectively. (C) 2000 Elsevier Science Ltd. All rights reserved.