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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 Δ-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.

Griseofulvin is an anti-fungal agent which has recently been determined to have potential anti-viral and anti-cancer applications. The role of specific enzymes involved in the biosynthesis of this natural product has previously been determined, but the mechanism by which a p450, GsfF, catalyzes the key oxidative cyclization of griseophenone B remains unknown. Using density functional theory (DFT), we have determined the mechanism of this oxidation that forms the oxa-spiro core of griseofulvin. Computations show GsfF preferentially performs two sequential phenolic O-H abstractions rather than epoxidation to form an arene oxide intermediate. This conclusion is supported by experimental kinetic isotope effects.