Isolation and Synthesis of Veranamine, an Antidepressant Lead from the Marine Sponge Verongula rigida

The natural product veranamine was isolated from the marine sponge Verongula rigida. It contains a unique heterocyclic scaffold and demonstrates in vivo antidepressant activity and selective affinity for 5HT2B and sigma-1 receptors. The first total synthesis of veranamine is reported. Our scalable synthesis offers veranamine in six steps and 25% yield via an unprecedented vinylogous Pictet–Gams pyridine formation strategy. Veranamine is a promising new lead compound for antidepressant drug development.