Synthesis of Photoswitchable Δ 9 -Tetrahydrocannabinol Derivatives Enables Optical Control of Cannabinoid Receptor 1 Signaling.

Autor: Westphal MV; Laboratorium für Organische Chemie, Eidgenössische Technische Hochschule Zürich , Vladimir-Prelog-Weg 3, 8093 Zürich, Switzerland., Schafroth MA; Laboratorium für Organische Chemie, Eidgenössische Technische Hochschule Zürich , Vladimir-Prelog-Weg 3, 8093 Zürich, Switzerland., Sarott RC; Laboratorium für Organische Chemie, Eidgenössische Technische Hochschule Zürich , Vladimir-Prelog-Weg 3, 8093 Zürich, Switzerland., Imhof MA; Laboratorium für Organische Chemie, Eidgenössische Technische Hochschule Zürich , Vladimir-Prelog-Weg 3, 8093 Zürich, Switzerland., Bold CP; Laboratorium für Organische Chemie, Eidgenössische Technische Hochschule Zürich , Vladimir-Prelog-Weg 3, 8093 Zürich, Switzerland., Leippe P; Department of Chemistry and Center for Integrated Protein Science, Ludwig Maximilians University Munich , Butenandtstraße 5-13, 81377 Munich, Germany., Dhopeshwarkar A; Department of Psychological and Brain Sciences and the Gill Center, Indiana University , Bloomington, Indiana 47405, United States., Grandner JM; Department of Biological Sciences and Department of Chemistry, Bridge Institute, University of Southern California , Los Angeles, California 90089, United States., Katritch V; Department of Biological Sciences and Department of Chemistry, Bridge Institute, University of Southern California , Los Angeles, California 90089, United States., Mackie K; Department of Psychological and Brain Sciences and the Gill Center, Indiana University , Bloomington, Indiana 47405, United States., Trauner D; Department of Chemistry and Center for Integrated Protein Science, Ludwig Maximilians University Munich , Butenandtstraße 5-13, 81377 Munich, Germany.; Department of Chemistry, New York University , 100 Washington Square East, New York, New York 10003-6699, United States., Carreira EM; Laboratorium für Organische Chemie, Eidgenössische Technische Hochschule Zürich , Vladimir-Prelog-Weg 3, 8093 Zürich, Switzerland., Frank JA; Department of Chemistry and Center for Integrated Protein Science, Ludwig Maximilians University Munich , Butenandtstraße 5-13, 81377 Munich, Germany.
Jazyk: angličtina
Zdroj: Journal of the American Chemical Society [J Am Chem Soc] 2017 Dec 20; Vol. 139 (50), pp. 18206-18212. Date of Electronic Publication: 2017 Dec 12.
DOI: 10.1021/jacs.7b06456
Abstrakt: The cannabinoid receptor 1 (CB1) is an inhibitory G protein-coupled receptor abundantly expressed in the central nervous system. It has rich pharmacology and largely accounts for the recreational use of cannabis. We describe efficient asymmetric syntheses of four photoswitchable Δ 9 -tetrahydrocannabinol derivatives (azo-THCs) from a central building block 3-Br-THC. Using electrophysiology and a FRET-based cAMP assay, two compounds are identified as potent CB1 agonists that change their effect upon illumination. As such, azo-THCs enable CB1-mediated optical control of inwardly rectifying potassium channels, as well as adenylyl cyclase.
Databáze: MEDLINE
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