Modular Approach to pseudo-Neoclerodanes as Designer κ-Opioid Ligands

Informed by previous semisynthetic work on salvinorin A, a modular total synthesis has been developed capable of producing novel compounds targeting the K-opioid receptor. The strategy has permitted the deliberate simplification and introduction of functionality about the target molecule to provide access to molecular features on salvinorin A otherwise unattainable by semisynthesis. Using this approach, a potent pseudo-neoclerodane kappa-opioid receptor ligand (2) has been realized.