Biosynthesis, total synthesis, and biological profiles of Ergot alkaloids

Synthesis of indole derivatives as prevalent moieties present in selected alkaloids

“…This research group tried to synthesize indolopyridocoline (319), norketoyobyrine (323), demethoxycarbonyl dihydrogambirtannine (324), rutaecarpine (329), isonaucledine triate (335), norepiisogeissoschizoate (336) and mitragynine (250). The total synthesis of indolopyridocoline (319) began with the Sonogashira coupling reaction of butyne-1-ol ( 313) and 2-bromopyridine (314), that afforded the corresponding alkyne 315. Then, the Larock indole annulation reaction of alkyne 315 and 2-bromoaniline (316) using palladium(II) acetate, 1,1 0 bis(diphenylphosphino) ferrocene (dppf), and potassium bicarbonate (KHCO 3 ) in DMF at 110 C gave the desired indole 317 with a 95% yield and a high regioselectivity.…”

“…The ergot alkaloids manufactured by the fungus Claviceps purpurea are a different group of naturally occurring indole compounds that show a wide range of powerful pharmacological properties. 313,314 Among the ergot alkaloids (EAs) family of naturally occurring compounds, lysergic acid 315 is the most broadly identied member and various semisynthetic derivatives have been clinically utilized for treating various neurological diseases. In 2015, Boger et al demonstrated 316 that the total synthesis of dihydrolysergic acid (363) and dihydrolysergol (364) relied on a palladium (0)-mediated intramolecular Larock indole cyclization for the formation of the tricyclic indole and also a consequently inverse electron demand Diels-Alder reaction.…”

Synthesis and Reactivity of Uhle’s Ketone and Its Derivatives

“…In addition, the total synthesis of ergoline compounds currently has experienced a remarkable renaissance, motivated by a spectrum of highly interesting bioactivities for this large family of natural products. 8 So, while this short review mainly focuses on synthetic achievements in the preparation and selective functionalization of 1 through the lens of illustrative literature examples, from Uhle's first use in 1949 until 2020, the authors have tried to place 1 into a wider context by including target ergot alkaloids and biologically active compounds. For clarity of presentation, the two sections, Giovanni Piersanti received his MS (Hons) in chemistry in 1997 from the University of Bologna where he remained to undertake two different fellowships by Farchemia (1998) and Glaxo-Wellcome (1999) under the supervision of Mauro Panunzio.…”

Biomimetic Total Syntheses of Ergot Alkaloids via Decarboxylative Giese Coupling

“…Ergot alkaloids are a group of classic indole alkaloids that feature the unique structure of a tetracyclic ring system (Figure ). Because of their structural similarities with dopamine, noradrenaline, and 5-hydroxytryptamine, these alkaloids play vital roles as agonists or antagonists of these three neurotransmitters. Therefore, they can be utilized for the treatment of neurodegenerative disease.…”

“…For example, the semisynthetic drug Pergolide is marketed as a therapeutic reagent for anti-Parkinson’s disease . Because of their unique structures and striking physiological properties, biosynthesis and total synthesis of ergot alkaloids have received longstanding attention . Since the first total synthesis of lysergic acid by Woodward in 1956, more than 20 routes have been reported.…”