Bioorganic & Medicinal Chemistry
May 1, 2012
Kimberly M Lovell, Tamara Vasiljevik, Juan J Araya et al.
35 citations
Modification of the furan ring of salvinorin A (1), the main active component of Salvia divinorum, has resulted in novel neoclerodane diterpenes with opioid receptor affinity and activity. Conversion of the furan ring to an aldehyde at the C-12 position (5) has allowed for the synthesis of analogues with new carbon-carbon bonds at that position. Previous methods for forming these bonds, such as...
Journal of Natural Products
April 25, 2011
Anthony Lozama, Christopher W Cunningham, Michael J Caspers et al.
40 citations
As part of our continuing efforts toward more fully understanding the structure-activity relationships of the neoclerodane diterpene salvinorin A, we report the synthesis and biological characterization of unique cycloadducts through [4+2] Diels-Alder cycloaddition. Microwave-assisted methods were developed and successfully employed, aiding in functionalizing the chemically sensitive salvinorin...
Topics in current chemistry
2011
Kimberly M Lovell, Katherine M Prevatt-Smith, Anthony Lozama et al.
17 citations
Salvinorin A is a neoclerodane diterpene that has been shown to be an agonist at kappa opioid receptors. Its unique structure makes it an attractive target for synthetic organic chemists due to its seven chiral centers and diterpene scaffold. This molecule is also interesting to pharmacologists because it is a non-serotonergic hallucinogen, and the first opioid ligand discovered that lacks a...
July 1, 2010
Anthony Lozama, Thomas E Prisinzano, David F. Wiemer et al.
1 citation
While there are a variety of therapeutics that interact with the opioid receptor system, they are not without side effects; including constipation, dysphoria and respiratory depression. A better understanding of the opioid receptor system may yield therapeutic agents with a limited side effect profile. The neoclerodane diterpene, salvinorin A, appears to interact at opioid receptors through a...
Organic & Biomolecular Chemistry
September 21, 2009
Denise S Simpson, Kimberly M Lovell, Anthony Lozama et al.
Further synthetic modification of the furan ring of salvinorin A (1), the major active component of Salvia divinorum, has resulted in novel neoclerodane diterpenes with opioid receptor affinity and activity. A computational study has predicted 1 to be a reproductive toxicant in mammals and is suggestive that use of 1 may be associated with adverse effects. We report in this study that...
Bioorganic & Medicinal Chemistry Letters
September 15, 2009
Anthony Lozama, Thomas E Prisinzano
Diterpenes are a structural class of molecules that are derived from four isoprene subunits and are widespread throughout nature. A number of neoclerodane diterpenes have been found to have biological activity but a limited number of chemical investigations have been conducted. Recently, the neoclerodane diterpene, salvinorin A (12) has been investigated due to its unique pharmacological...
Journal of Medicinal Chemistry
April 24, 2008
Kevin Tidgewell, Chad E Groer, Wayne W Harding et al.
Salvinorin A is a psychoactive natural product that has been found to be a potent and selective kappa opioid receptor agonist in vitro and in vivo. The activity of salvinorin A is unusual compared to other opioids such as morphine in that it mediates potent kappa opioid receptor signaling yet leads to less receptor downregulation than observed with other kappa agonists. Our initial chemical...
Journal of Medicinal Chemistry
July 26, 2007
Denise S Simpson, Peter L Katavic, Anthony Lozama et al.
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...
Journal of Natural Products
June 2006
Kevin Tidgewell, Wayne W Harding, Anthony Lozama et al.
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...