Riddelliine is a chemical compound classified as a pyrrolizidine alkaloid. It was first isolated from Senecio riddellii and is also found in a variety of plants including Jacobaea vulgaris, Senecio vulgaris, and others plants in the genus Senecio. Riddelliine can be found as a contaminant in foods such as meat, grains, seeds, milk, herbal tea, and honey. Riddelliine is suspected to be a carcinogen. It is listed as an IARC Group 2B carcinogen and listed by the National Toxicology Program in its Report on Carcinogens which lists chemicals "known or reasonably anticipated to cause cancer in humans". Structure and Reactivity Riddelliine is a naturally occurring pyrrolizidine alkaloid, a class of compounds occurring in rangeland plants of the genera Crotalaria, Amsinckia, and Senecio. It consists of a macrocyclic diester of retronecine (an unsaturated alcohol) and riddelliic acid (an oxygenated, branched, dicarboxylic acid). Riddelliine is a colorless to off-white crystalline solid at room temperature and has a melting point of 197° to 198 °C. It is soluble in chloroform, acetone, and ethanol, and is sparingly soluble in water. As a solid, it is stable at room temperature in diffuse light for 12 months or longer. Alcoholic and aqueous solutions of riddelliine are stable at room temperature when protected from light. It emits toxic fumes of nitrogenoxide when heated to decomposition. Synthesis Riddelliine is produced naturally by a variety of plants in the genus Senecio. In particular, the Senecio riddelliispecies (commonly referred to as Riddell's ragwort) can attribute up to 18% of its total weight to riddelliine and its N-oxide counterpart, riddelliine N-oxide. Like other pyrrolizidine alkaloids, the synthesis of riddelliine involves the conversion of ornithine and arginine into retronecine. A traced synthesis shows that arginine (or its precursor ornithine) is converted into putrescine, which then gets converted into homospermidine. Homospermidine is then oxidized into dialdehydeamine, which undergoes an intramolecular Mannich reaction to produce trachelanthamidine. Trachelanthamidine is converted into supinidine, the final intermediate to producing retronecine. Retronecine is then reacted with riddelliic acid to produce riddelliine. A chemical synthesis of riddelliine has not yet been established. Mechanism Riddelliine itself is not toxic; rather its metabolism in the liver contributes to its toxicity. Riddelliine can be hydrolyzed in the liver into riddelliine N-oxide, which like riddelliine is not a toxic substance. This pathway is considered a detoxicating reaction. On the other hand, riddelliine can be dehydrated by Cytochrome P450 to produce dehydroriddelliine. Two possible