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 – January 01, 2006
Source: PubMed
Summary
Salvinorin A, a unique hallucinogen, is the first non-nitrogenous opioid receptor ligand. Its unique receptor binding is a mystery; altering its structure could unlock secrets. Scientists explored chemical transformations of Salvinorin A, successfully semisynthesizing salvinicins A and B. Remarkably, they identified compound 10a as the first neoclerodane diterpene with delta opioid antagonist activity, significantly advancing our understanding of these complex molecules.
Abstract
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 kappa opioid receptors. One approach to better understanding the mode of binding of 1 at kappa 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 delta opioid antagonist activity.