Synthetic studies of neoclerodane diterpenes from Salvia divinorum: preparation and opioid receptor activity of salvinicin analogues.
نویسندگان
چکیده
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.
منابع مشابه
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 opioid receptors. One approach to better understanding the mode of binding of 1 at kappa receptors ...
متن کاملSynthetic studies of neoclerodane diterpenes from Salvia divinorum: role of the furan in affinity for opioid receptors.
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 piperidin...
متن کاملSalvinicins A and B, new neoclerodane diterpenes from Salvia divinorum.
[reaction: see text] Two new neoclerodane diterpenes, salvinicins A (4) and B (5), were isolated from the dried leaves of Salvia divinorum. The structures of these compounds were elucidated by spectroscopic techniques, including (1)H and (13)C NMR, NOESY, HMQC, and HMBC. The absolute stereochemistry of these compounds was assigned on the basis of single-crystal X-ray crystallographic analysis o...
متن کاملSynthesis 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 struct...
متن کاملSynthesis and κ-Opioid Receptor Activity of Furan-Substituted Salvinorin A Analogues
The neoclerodane diterpene salvinorin A, found in the leaves of Salvia divinorum, is a potent κ-opioid receptor agonist, making it an attractive scaffold for development into a treatment for substance abuse. Although several successful semisynthetic studies have been performed to elucidate structure-activity relationships, the lack of analogues with substitutions to the furan ring of salvinorin...
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ورودعنوان ژورنال:
- Journal of medicinal chemistry
دوره 50 15 شماره
صفحات -
تاریخ انتشار 2007