Ingenol mebutate is a substance found in the sap of the plant Euphorbia peplus and an inducer of cell death. A gel formulation of the drug has been approved by the U.S. Food and Drug Administration (FDA) and by the European Medicines Agency (EMA) for the topical treatment of actinic keratosis. Two different strengths of the gel are approved for use on either the face and scalp (0.015%) or the trunk and extremities (0.05%), respectively. Results from four multicenter, randomized, double-blind studies have shown that ingenol mebutate gel applied topically for 2 to 3 days is effective for field treatment of actinic keratoses. The substance is an ester of the diterpene ingenol and angelic acid. A 3-step semisynthesis of ingenol mebutate starting from ingenol was described. A 14-step synthesis of (+)-ingenol from (+)-3-carene, which is a relatively inexpensive constituent of turpentine, was published in July 2013.
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