Synthesis of salvinorin A analogues as opioid receptor probes.
Several neoclerodanes, such as salvinorin A (1) and herkinorin (3), have recently been shown to possess opioid receptor activity in vitro and in vivo. To explore the structure-affinity relationships of this interesting class of compounds, we have synthesized a series of analogues from 1 isolated from Salvia divinorum. Here, we report the semisynthesis of neoclerodane diterpenes and their structure-affinity relationships at opioid receptors. This work will allow the further development of novel opioid receptor ligands.
Tidgewell
Kevin
K
Division of Medicinal & Natural Products Chemistry, College of Pharmacy, The University of Iowa, Iowa City, Iowa 52242, USA.
Harding
Wayne W
WW
Lozama
Anthony
A
Cobb
Howard
H
Shah
Kushal
K
Kannan
Pavitra
P
Dersch
Christina M
CM
Parrish
Damon
D
Deschamps
Jeffrey R
JR
Rothman
Richard B
RB
Prisinzano
Thomas E
TE
D018360:Crystallography, X-Ray; D004224:Diterpenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D045785:Diterpenes, Clerodane; D008968:Molecular Conformation; D015394:Molecular Structure; D010946:Plants, Medicinal / Q000737:chemistry*; D011957:Receptors, Opioid / Q000819:agonists*; D027544:Salvia / Q000737:chemistry*; D013329:Structure-Activity Relationship
D004224:Diterpenes; D045785:Diterpenes, Clerodane; D011957:Receptors, Opioid; C090499:salvinorin A