Solving a Mystery with Classical and Dual Photoredox Catalysis: Application of Nickel in the Synthesis of Ergot Alkaloids.
Organic letters – May 24, 2024
Source: PubMed
Summary
Scientists have achieved a breakthrough in producing ergot alkaloids - naturally occurring compounds with important medicinal properties - using an innovative dual-catalyst approach. By employing nickel instead of traditional palladium catalysts, researchers developed a more efficient way to synthesize these valuable molecules, including precursors to therapeutic compounds. This method resolves previous synthesis challenges and offers a more sustainable path forward.
Abstract
A short synthesis of the ergot alkaloid lysergene and a formal total synthesis of lysergic acid diethylamide (LSD) under the avoidance of palladium and including two nickel-catalyzed steps instead have been developed. A key intermediate of this approach has already been reported by Hendrickson et al. in 2004 (Hendrickson, J.B. et al. Org. Lett. 2004, 6, 3-5), yet the spectral data do not match, adding to doubts about the course of their route. While the final steps of the Hendrickson synthesis could not be reproduced, we were able to leverage the elusive intermediate.