Synthesis and cannabinoid receptor activity of ketoalkenes from Echinacea pallida and nonnatural analogues.
Despite its popularity and widespread use, the efficacy of Echinacea products remains unclear and controversial. Among the various compounds isolated from Echinacea, ketoalkenes and ketoalkenynes exclusively found in the pale purple coneflower (E. pallida) are major components of the extracts. In contrast to E. purpurea alkamides, these compounds have not been synthesized and studied for immunostimulatory effects. We present a practical and useful synthetic approach to the ketoalkenes using palladium-catalyzed cross-coupling reactions and the pharmaceutical results at the human cannabinoid receptors. The synthetic route developed provides overall good yields for the ketoalkenes and is applicable to other natural products with similar 1,4-diene motifs. No significant activity was observed at either receptor, indicating that the ketoalkenes from E. pallida are not responsible for immunomodulatory effects mediated via the cannabinergic system. However, newly synthesized non-natural analogues showed micro-molar potency at both cannabinoid receptors.
Egger
Michael
M
Institut für Organische Chemie, Universität Regensburg, 93040 Regensburg, Germany.
Pellett
Patrina
P
Nickl
Kathrin
K
Geiger
Sarah
S
Graetz
Stephanie
S
Seifert
Roland
R
Heilmann
Jörg
J
König
Burkhard
B
D000473:Alkanes / Q000138:chemical synthesis / Q000494:pharmacology; D001688:Biological Products / Q000737:chemistry* / Q000494:pharmacology; D020900:Echinacea / Q000737:chemistry*; D006801:Humans; D007659:Ketones / Q000138:chemical synthesis / Q000494:pharmacology*; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D010946:Plants, Medicinal / Q000737:chemistry; D043884:Receptor, Cannabinoid, CB1 / Q000187:drug effects; D043885:Receptor, Cannabinoid, CB2 / Q000187:drug effects; D043882:Receptors, Cannabinoid / Q000187:drug effects*
D000473:Alkanes; D001688:Biological Products; D007659:Ketones; D010936:Plant Extracts; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; D043882:Receptors, Cannabinoid