Synfacts 2021; 17(01): 0019
DOI: 10.1055/s-0040-1719268
Synthesis of Natural Products and Potential Drugs

Total Synthesis of (±)-Lysergic Acid

Contributor(s):
Erick M. Carreira
,
Moritz J. Classen
Oppolzer W, *, Francotte E, Bättig K. University of Geneva, Switzerland
Total Synthesis of (±)-Lysergic Acid by an Intramolecular Imino-Diels–Alder Reaction.

Helv. Chim. Acta 1981;
64: 478-481
DOI: 10.1002/hlca.19810640212.
 

Significance

In 1981, Oppolzer and co-workers reported a concise synthesis of (±)-lysergic acid, a precursor for many ergoline alkaloids. Their synthesis improved upon earlier approaches in terms of efficiency and length by utilizing a Diels–Alder cycloaddition as the key step.


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Comment

Intermediate F was accessed from 4-hydroxymethyl-1-tosylindole (A) in four steps and was converted to J either directly by treatment with G, or more efficiently over two steps. Nef reaction gave rise to K, which underwent retro-Diels–Alder followed by Diels–Alder cycloaddition in one pot at 200 °C. Three more steps gave (±)-lysergic acid.


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Publication History

Publication Date:
16 December 2020 (online)

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