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

doi:10.1021/jacs.7b06456

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 journal › Article › peer-review

73 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 language	English (US)
Pages (from-to)	18206-18212
Number of pages	7
Journal	Journal of the American Chemical Society
Volume	139
Issue number	50
DOIs	https://doi.org/10.1021/jacs.7b06456
State	Published - Dec 20 2017
Externally published	Yes

ASJC Scopus subject areas

Catalysis
General Chemistry
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. 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

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

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title = "Synthesis of Photoswitchable9-Tetrahydrocannabinol Derivatives Enables Optical Control of Cannabinoid Receptor 1 Signaling",

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.",

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

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AU - Imhof, Michael A.

AU - Bold, Christian P.

AU - Leippe, Philipp

AU - Dhopeshwarkar, Amey

AU - Grandner, Jessica M.

AU - Katritch, Vsevolod

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

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