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 SHT2B 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. Veranmine is a promising new lead compound for antidepressant drug development.