The Plakotenins: Biomimetic Diels-Alder Reactions, Total Synthesis, Structural Investigations, and Chemical Biology

The total synthesis of plakotenin, a cytotoxic marine natural product, using a biomimetic DielsAlder reaction is described in detail. Two approaches were used, whereby the DielsAlder reaction occurs at different stages of the synthesis. Homo- and nor-plakotenin, related natural products, were also prepared, as well as iso-plakotenin, a diastereoisomer of plakotenin. The syntheses prove the relative and absolute stereochemistry of the latter. The chemical biology of the plakotenins was investigated on selected compounds.