Total Synthesis of Mangicol A

A stereoselective total synthesis of the pharmacologically active and structurally interesting tetracyclic C25 terpene Mangicol A will be developed. Mangicol A was isolated from the marine fungi Fusarium heterosprum. This secondary metabolite displays interesting biological properties ranging from modest cytotoxicity towards a variety of cancer cell lines in in vitro testing to significant anti-inflammatory activity in the PMA (phorbol myristate acetate)-induced mouse ear edema model. Despite this interesting biological profile, the synthesis of this complex carbon skeleton has not yet been reported. Mangicol A contains 11 chiral centers and a novel spirotricyclic skeleton. The first key step in our convergent synthetic approach to a tricyclic carbon skeleton intermediate is an intramolecular Diels-Alder (IMDA) reaction of an ester, with a predicted kinetically controlled exo transition state. The second key step, a [2+2] photocyclisation reaction using the IMDA adduct, should afford an intermediate with a four membered ring, which upon a radical ring fragmentation results in the tetracyclic ring system of Mangicol A.