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 A. Frank

Research output: Contribution to journalArticle

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

Fingerprint

Cannabinoid Receptors
Dronabinol
Derivatives
Electrophysiology
Neurology
Cannabinoid Receptor Agonists
Inwardly Rectifying Potassium Channel
Potassium
Assays
Cannabis
G-Protein-Coupled Receptors
Lighting
Adenylyl Cyclases
Proteins
Central Nervous System
Pharmacology
Cannabinoids

ASJC Scopus subject areas

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

Cite this

Westphal, M. V., Schafroth, M. A., Sarott, R. C., Imhof, M. A., Bold, C. P., Leippe, P., ... Frank, J. A. (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

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

In: Journal of the American Chemical Society, Vol. 139, No. 50, 20.12.2017, p. 18206-18212.

Research output: Contribution to journalArticle

Westphal, MV, Schafroth, MA, Sarott, RC, Imhof, MA, Bold, CP, Leippe, P, Dhopeshwarkar, A, Grandner, JM, Katritch, V, Mackie, K, Trauner, D, Carreira, EM & Frank, JA 2017, 'Synthesis of Photoswitchable9-Tetrahydrocannabinol Derivatives Enables Optical Control of Cannabinoid Receptor 1 Signaling', Journal of the American Chemical Society, vol. 139, no. 50, pp. 18206-18212. https://doi.org/10.1021/jacs.7b06456
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. / Synthesis of Photoswitchable9-Tetrahydrocannabinol Derivatives Enables Optical Control of Cannabinoid Receptor 1 Signaling. In: Journal of the American Chemical Society. 2017 ; Vol. 139, No. 50. pp. 18206-18212.
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