TY - JOUR
T1 - Synthetic studies of neoclerodane diterpenes from Salvia divinorum
T2 - Semisynthesis of salvinicins A and B and other chemical transformations of salvinorin A
AU - Harding, Wayne W.
AU - Schmidt, Matthew
AU - Tidgewell, Kevin
AU - Kannan, Pavitra
AU - Holden, Kenneth G.
AU - Gilmour, Brian
AU - Navarro, Hernan
AU - Rothman, Richard B.
AU - Prisinzano, Thomas E.
PY - 2006/1
Y1 - 2006/1
N2 - 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 κ opioid receptors. One approach to better understanding the mode of binding of 1 at κ 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 δ opioid antagonist activity.
AB - 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 κ opioid receptors. One approach to better understanding the mode of binding of 1 at κ 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 δ opioid antagonist activity.
UR - http://www.scopus.com/inward/record.url?scp=32644449608&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=32644449608&partnerID=8YFLogxK
U2 - 10.1021/np050398i
DO - 10.1021/np050398i
M3 - Article
C2 - 16441078
AN - SCOPUS:32644449608
SN - 0163-3864
VL - 69
SP - 107
EP - 112
JO - Journal of Natural Products
JF - Journal of Natural Products
IS - 1
ER -