Synthetic studies of neoclerodane diterpenes from Salvia divinorum: Semisynthesis of salvinicins A and B and other chemical transformations of salvinorin A
Salvinorin A (1) is a hallucinogenic neoclerodane diterpene isolated from the widely available psychoactive plant Salvia divinorum and is the first example of a non-nitrogenous opioid receptor ligand. At present, there is little information available as to why this compound is selective for ? opioid receptors. One approach to better understanding the mode of binding of 1 at ? receptors is to systematically alter the structure of 1 and examine the effects on opioid receptor affinity and activity. Currently, there is a paucity of methods described for the preparation of analogues derived from 1. Here, we report the investigation of several chemical transformations of 1 isolated from S. divinorum. In particular, this work provides a semisynthesis of salvinicins A (2) and B (3) and has identified 10a as the first neoclerodane diterpene with ? opioid antagonist activity.
Harding, WW., Schmidt, M., Tidgewell, K., Kannan, P., Holden, KG., Gilmour, B., ... Prisinzano, TE. (2006). Synthetic studies of neoclerodane diterpenes from Salvia divinorum: Semisynthesis of salvinicins A and B and other chemical transformations of salvinorin A. Journal of Natural Products, 69(1), 107-112. DOI: 10.1021/np050398i