Total Synthesis of (±)-Lysergic Acid

Key words

lysergic acid - Diels–Alder reaction - Appel reaction - Nef reaction - Wittig olefination - Mannich reaction - ergoline alkaloids

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.

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.

Publication History

Article published online:
16 December 2020