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 kappa op...

Full description

Saved in:
Bibliographic Details
Published in:Journal of natural products (Washington, D.C.) D.C.), 2006-01, Vol.69 (1), p.107-112
Main Authors: Harding, W.W, Schmidt, M, Tidgewell, K, Kannan, P, Holden, K.G, Gilmour, B, Navarro, H, Rothman, R.B, Prisinzano, T.E
Format: Article
Language:English
Subjects:
Biological and medical sciences
Diterpenes - chemical synthesis
Diterpenes - chemistry
Diterpenes - pharmacology
Diterpenes, Clerodane - chemical synthesis
Diterpenes, Clerodane - chemistry
Diterpenes, Clerodane - pharmacology
diterpenoids
General pharmacology
Humans
Medical sciences
Molecular Structure
neoclerodane
Neuropharmacology
Neurotransmitters. Neurotransmission. Receptors
Peptidergic system (neuropeptide, opioid peptide, opiates...). Adenosinergic and purinergic systems
Pharmacognosy. Homeopathy. Health food
Pharmacology. Drug treatments
Plants, Medicinal - chemistry
Receptors, Opioid, delta - antagonists & inhibitors
Receptors, Opioid, mu - antagonists & inhibitors
Salvia
Salvia - chemistry
Salvia divinorum
salvinicin
salvinorin
Stereoisomerism
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0163-3864
1520-6025
DOI:10.1021/np050398i