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.
D000998:Antiviral Agents / Q000138:chemical synthesis*; D016590:Aphidicolin; D002460:Cell Line; D002472:Cell Transformation, Viral; D055598:Chemical Phenomena; D002621:Chemistry; D004261:DNA Replication / Q000187:drug effects*; D004224:Diterpenes / Q000138:chemical synthesis / Q000494:pharmacology; D006801:Humans; D007202:Indicators and Reagents; D008168:Lung; D009682:Magnetic Resonance Spectroscopy; D013539:Simian virus 40 / Q000235:genetics; D013055:Spectrophotometry, Infrared; D013329:Structure-Activity Relationship
D000998:Antiviral Agents; D004224:Diterpenes; D007202:Indicators and Reagents; D016590:Aphidicolin