Biosynthesis of Ergot Toxins

Microbial Secondary Metabolites Play Important Roles in Medicine; Prospects for Discovery of New Drugs

“…In 1919, Stoll described the first pure material from ergot [39]. It was ergotamine, an alkaloid with the basic four-ring structure of ergoline and a cyclol-type peptide component [37,38]. On hydrolysis, it yields the now well-known lysergic acid; the even more infamous diethylamide of lysergic acid, LSD, was prepared in 1938.…”

“…On hydrolysis, it yields the now well-known lysergic acid; the even more infamous diethylamide of lysergic acid, LSD, was prepared in 1938. It is a powerful hallucinogen, with 0.02-0.03 mg of LSD being sufficient to cause hallucinations [38] .…”

“…There was, however, another side to ergot, since preparations from it were used as a drug. The first written description of this usage was in 1582, and eventually it came to be used by midwives to promote uterine contractions and prevent bleeding during childbirth [36][37][38].…”

Liquid chromatography–tandem mass spectrometry characterization of ergocristam degradation products

“…Structures of these compounds were assigned by 1 H and/or 13 C NMR and mass spectrometry with electron impact [8,9] and fast atom bombardment ionization [10]. A role of ergopeptams in biogenesis of the peptide part of ergot alkaloids has been studied by Floss and co-workers [11][12][13] who described an effect of competitive reaction bringing about a reversal of configuration of optically active carbon of l-proline to the d-configuration. The resulting compound cannot enter the biochemical reaction which leads to the formation of a non cyclol structure.…”

Direct Olefination at the C-4 Position of Tryptophan via C–H Activation: Application to Biomimetic Synthesis of Clavicipitic Acid

“…One of these compounds, the lysergic acid diethylamide (LSD), is strongly and notoriously psychoactive. The commonly accepted biosynthesis pathway for the ergot alkaloids is initiated by prenylation of tryptophan with dimethylallyl pyrophosphate ( 1 ) (DMAPP) to yield 4-dimethylallyltryptophane ( 2 ) (DMAT) . Subsequent transformations led to different classes of ergot alkaloids (Scheme ).…”