Biosynthesis of Ergot Alkaloids

맥각 알칼로이드의 생합성

Recent findings that agroclavine strongly inhibits: lactation and that ergocornine and ergonovine induce regression or inhibition of pituitary tumor growth in rats revealed new pharmacological activities in addition to the well-known activities of ergot alkaloids. Clavicipitic acid, isochanoclavine (I) and chanoclavine (II) are newly isolated alkaloids. It was already established that tryptophan, mevalonic acid and methionine are biosynthetic precursors of ergoline, a basic structure of the alkaloids, which is formed via $4-({\gamma},{\gamma}-dimethylallyl)-tryptophan$, mediated by dimethylallylpyrophosphate: tryptophan dimethylallyl transferase. Chanoclavine-I appears to be an intermediate to agroclavine which is converted to elymoclavine. Agroclavine and elymoclavine were also found to be hydroxylated by peroxidase to setoclavine and penniclavine, respectively. Elymoclavine is converted to ergotamine and lysergic acid ${\alpha}-hydroxyethylamide$, respectively. Pyruvate and alanine were found to be incorporated into the two-carbon unit of the ${\alpha}-hydroxyethyl$ moiety of the latter. Lysergylalanine is converted to ergometrine, but not to lysergic acid ${\alpha}-hydroxyethylamide$.