Cycloclavine is an ergot alkaloid. It was first isolated in 1969 from seeds of Ipomoea hildebrandtii vatke. The first total synthesis of (±)-cycloclavine was published in 2008 by Szántay. Further reports came from Wipf and Petronijevic, Cao and Brewer. In 2016, Wipf and McCabe completed an 8-step asymmetric synthesis of (–)-cycloclavine, and in 2018, they expanded this approach toward ( )-cycloclavine and a biological characterization of the binding profile of both enantiomers on 16 brain receptors. Natural ( )- and unnatural (–)-cycloclavine demonstrated significant stereospecificity and unique binding profiles in comparison to LSD (lysergic acid diethylamide), psilocin, and DMT. Differential 5-HT receptor affinities, as well as novel sigma-1 receptor properties, suggest potential future therapeutic opportunities of clavine alkaloid scaffolds.
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