Progress towards the total synthesis of palau'amine

ORGN 198

Shaohui Wang,, Department of Chemistry, Texas A&M University, TAMU, College Station, TX 77842-3012 and Daniel Romo,, Department of Chemistry, Texas A & M University, P.O. Box 30012, College Station, TX 77842-3012.
Palau'amine was isolated from the Belau sponge Stylotella aurantium by Kinnel and Scheuer in 1993 and was found to possess potent immunosuppressive activity (MLR IC50<42.8 nM) and tumor cytotoxicity. This complex, hexacyclic marine natural product belongs to the oroidin-derived family of secondary metabolites and contains a fully substituted chloro-cyclopentane ring. Our synthetic strategy to the complex cyclopentane core is premised on a biosynthetic proposal suggested by Kinnel and Scheuer and involves a Diels-Alder/chlorination/ring contraction sequence. We envisioned that phakellin annulation would provide palau'amine from the tricyclic core structure. The phakellin annulation process is based on our synthetic strategy for phakellstatin. Our current studies focus on the installation of the chlorine atom to the cyclopentane core. Strategies entailing various intramolecular chlorinations are being investigated and alternative routes will also be presented.