Synthesis of a tricyclic aphidicolin analogue that inhibits DNA synthesis in vitro.

We have hypothesized that the biological activity of the antiviral antitumor diterpene aphidicolin requires a specific stereochemical relationship between two rigidly held hydroxyl groups on the alpha face of the molecule. The complex tetracyclic carbon skeleton is not necessary but appears to serve only as a framework on which to hold the hydroxyls. In support of this theory, we have prepared a simple tricyclic triol analogue (7) whose activity approaches that of the natural product in inhibiting in vitro DNA synthesis.