Synthesis of Photoswitchable Delta(9)-Tetrahydrocannabinol Derivatives Enables Optical Control of Cannabinoid Receptor 1 Signaling

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 Delta(9)-tetrahydroc...

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Bibliographic Details
Published inJournal of the American Chemical Society Vol. 139; no. 50; pp. 18206 - 18212
Main Authors Westphal, Matthias V., Schafroth, Michael A., Sarott, Roman C., Imhof, Michael A., Bold, Christian P., Leippe, Philipp, Dhopeshwarkar, Amey, Grandner, Jessica M., Katritch, Vsevolod, Mackie, Ken, Trauner, Dirk, Carreira, Erick M., Frank, James A.
Format Journal Article
LanguageEnglish
Published WASHINGTON Amer Chemical Soc 20.12.2017
Subjects
Chemistry
Chemistry, Multidisciplinary
Physical Sciences
Science & Technology
CONSTITUENT
CELLS
INHIBITION
DESENSITIZATION
PHARMACOLOGY
RAT-BRAIN
EXPRESSION
AGONIST
TOOLS
PHOTOPHARMACOLOGY
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Summary: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 Delta(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.
ISSN:0002-7863
1520-5126
DOI:10.1021/jacs.7b06456