Carreira EM,
*,
Frank A.
*
et al.
Eidgenössische Technische Hochschule Zürich, Switzerland and Oregon Health & Science
University, Portland, USA
Optical Control of Cannabinoid Receptor 2-Mediated Ca
2+ Release Enabled by Synthesis of Photoswitchable Probes.
J. Am. Chem. Soc. 2021;
143: 736-743
DOI:
10.1021/jacs.0c08926
Key words
G protein-coupled receptors - photoswitches - azobenzenes
Significance
Cannabinoid receptor 2 (CB2) is a G protein-coupled receptor with important roles
in immunobiology. Pharmacological regulation holds promise for the treatment of neurological
disorders. Photoswitchable probes would offer high spatiotemporal control, leading
to new insights into CB2 signaling. The Carreira and Frank groups describe the development
of azo-HU308-3, a probe that is inactive in the dark and can be activated upon irradiation with
375 nm light.
Comment
A series of three HU308-derived photoswitches (azo-HU308-1–3) were synthesized from the terpene (+)-verbenone. 3-OTf-HU308 could be accessed in seven robust and high-yielding steps. Azobenzene photoswitches
were attached to this intermediate using Buchwald–Hartwig or Suzuki–Miyaura couplings
with potassium trifluoroborate reagents C and D as pioneered by Molander (Synlett
2005, 1763).
