Synthesis of Photoswitchable9-Tetrahydrocannabinol Derivatives Enables Optical Control of Cannabinoid Receptor 1 Signaling

Matthias V. Westphal, Michael A. Schafroth, Roman C. Sarott, Michael A. Imhof, Christian P. Bold, Philipp Leippe, Amey Dhopeshwarkar, Jessica M. Grandner, Vsevolod Katritch, Ken Mackie, Dirk Trauner, Erick M. Carreira, James Frank

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

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 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.

Original languageEnglish (US)
Pages (from-to)18206-18212
Number of pages7
JournalJournal of the American Chemical Society
Volume139
Issue number50
DOIs
StatePublished - Dec 20 2017
Externally publishedYes

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

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    Westphal, M. V., Schafroth, M. A., Sarott, R. C., Imhof, M. A., Bold, C. P., Leippe, P., Dhopeshwarkar, A., Grandner, J. M., Katritch, V., Mackie, K., Trauner, D., Carreira, E. M., & Frank, J. (2017). Synthesis of Photoswitchable9-Tetrahydrocannabinol Derivatives Enables Optical Control of Cannabinoid Receptor 1 Signaling. Journal of the American Chemical Society, 139(50), 18206-18212. https://doi.org/10.1021/jacs.7b06456