Synthesis and Biological Evaluation of 3′,5′-d2-Cannabidiol

Cannabidiol (CBD) is the primary active pharmacologic component in Cannabis sativa l., which is non-psychoactive. CBD shows anti-tumor, anti-inflammatory, sedative and many other activities, thus demonstrating potential therapeutic utilities in neurodegenerative diseases, epilepsy, cancer and other diseases. There have been numerous pharmacokinetic studies of CBD, which indicate the main metabolic sites are 6- and 7-position of monoterpene and alkyl chain of the olivetol. While only few studies are available for the metabolic sites of the benzene ring. In this paper, the aromatic hydrogen on the benzene ring was deuterated, and the antitumor activity, hERG potassium channel activity and liver microsome stability of 3′,5′-d2-cannabidiol (D2CBD) and CBD were compared. The results show that the antitumor activity and hERG potassium channel activity are slightly improved, whereas liver microsomes stability of D2CBD is not significantly improved.