Synthesis of the novel anti-leukaemic tetrahydrocyclopenta[b]benzofuran, rocaglamide and related synthetic studies

Two approaches to the rocaglamide tricyclic skeleton are described. The first, which employs an unusual intramolecular dithianyl anion to carbonyl addition reaction, provides access to α-phenyl rocaglamide analogues. The second route involves an intramolecular keto aldehyde pinacolic coupling in the key step and can be used for the preparation of a whole range of rocaglamide analogues possessing both α- and β-phenyl substituents. A total synthesis of rocaglamide, in racemic form, is described using this second approach. The synthetic route commences with phloroglucinol, an inexpensive and readily-available starting material, and takes only 8/9 steps giving an overall yield of >6%. The synthesis of 1-epi-rocaglamide 29b is also described.