Total synthesis of the marine sesquiterpenoid raikovenal through a novel utilization of the bicyclo[3.2.0]heptenone approach

In 1994, Pietra and co-workers 1 isolated from the marine ciliate Euplotes raikovi Amagaliev, stock Morl, collected along Atlantic coasts near Casablanca, the architecturally unusual sesquiterpenoid 1 termed raikovenal and its putative biogenetic precursor (preraikovenal). The structure and relative stereochemistry of 1 were deduced on the basis of extensive NMR studies. The main part of the molecular array is the bicyclo[3.2.0]heptane core with the five-carbon side chain, the hydroxylated α,β-unsaturated aldehyde, in a strictly defined geometric setting. Whereas the effectiveness of raikovenal in favoring adaptive radiation of marine ciliate E. raikovi was clearly demonstrated,1 no synthesis of this interesting marine natural product has been reported until now. Recently, an efficient approach to the stereoselective synthesis of natural products based on the practical preparation and selective utilization of bicyclo[3.2.0]hept-3-en-6-ones 2,3 has been devised and developed in our laboratories. In this paper we present (Scheme 1) the stereoselective synthesis of racemic raikovenal through the application of this bicyclization methodology.