Studies towards the synthesis of aplykurodins - Synthesis of 17,18-dihydro-3,9-di-epi-aplykurodinone B

An approach to the synthesis of aplykurodins, ichthyotoxic marine lactones, is presented. The carbon framework was derived from vitamin D3 by conversi on of the readily accessible allyl alcohol 13 to the protected Grundmann's hydroxy ketone 22 and subsequent introduction of the C2 side chain through a Pd-0-promoted coupling. Highly stereoselective hetero Diels-Alder reactio n with O2(1) produced the key intermediate peroxide 25. Functional group tr ansformations, coupled with a series of chemo- and stereoselective reaction s, finally resulted in the synthesis of the unnatural analogue 17,18-dihydr o-3,9-di-epi-aplykurodinone B (6).