Synthetic studies of neoclerodane diterpenes from Salvia divinorum: preparation and opioid receptor activity of salvinicin analogues.
Further modification of salvinorin A (1a), the major active component of Salvia divinorum, has resulted in the synthesis of novel neoclerodane diterpenes with opioid receptor affinity and activity. We report in this study that oxadiazole 11a and salvidivin A (12a), a photooxygenation product of 1a, have been identified as the first neoclerodane diterpenes with kappa antagonist activity. This indicates that additional structural modifications of 1a may lead to analogues with higher potency and utility as drug abuse medications.
Simpson
Denise S
DS
Division of Medicinal & Natural Products Chemistry, College of Pharmacy, The University of Iowa, Iowa City, Iowa 52242, USA.
Katavic
Peter L
PL
Lozama
Anthony
A
Harding
Wayne W
WW
Parrish
Damon
D
Deschamps
Jeffrey R
JR
Dersch
Christina M
CM
Partilla
John S
JS
Rothman
Richard B
RB
Navarro
Hernan
H
Prisinzano
Thomas E
TE
D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D018360:Crystallography, X-Ray; D045785:Diterpenes, Clerodane / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D005663:Furans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D015394:Molecular Structure; D011869:Radioligand Assay; D017465:Receptors, Opioid, delta / Q000819:agonists / Q000037:antagonists & inhibitors; D017473:Receptors, Opioid, kappa / Q000819:agonists / Q000037:antagonists & inhibitors*; D017450:Receptors, Opioid, mu / Q000819:agonists / Q000037:antagonists & inhibitors; D027544:Salvia / Q000737:chemistry*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D045785:Diterpenes, Clerodane; D005663:Furans; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; C509586:salvinicin A; C509587:salvinicin B