Approaches to the synthesis of ingenol

Ingenol is a highly oxygenated tetracyclic diterpene which mimics the function of diacylglycerol, the endogenous activator of protein kinase C. One of the most imposing challenges in the synthesis of ingenol is the establishment of the highly strained 'inside-outside' or trans-intrabridgehead stereochemical relationship of the carbocyclic ring system of the ingenanes, The approaches that have been examined in several laboratories towards the synthesis of the ingenanes are summarized, Our own work, using the intramolecular dioxenone photocycloaddition to establish this unique stereochemical feature, is described.