Cannabidiol synthesis

The lUPAC name of cannabidiol is 2-[(lS, 6iI)-3-methyl-6-prop-l-en-2-yl-l-cyclohex-2-enyl]-5-pentyl-benzene-1,3-diol. Cannabidiol (CBD, 2.9) in its acidic form cannabidiolic acid (CBDA, 2.10) is the second major cannabinoid in C. sativa besides A9-THC. As already mentioned for A9-THC, variations in the length of the side chain are also possible for CBD. Important in this context are the propyl side chain-substituted CBD, named cannabidivarin (CBDV, 2.11), and CBD-C4 (2.12), the homologous compound with a butyl side chain. Related to the synthesis starting from CBD to A9-THC as described in Sect. 3.1, it was accepted that CBDA serves as a precursor for THCA in the biosynthesis. Recent publications indicate that CBDA and THCA are formed from the same precursor, cannabigerolic acid (CBGA), and that it is unlikely that the biosynthesis of THCA from CBDA takes place in C. sativa. 

Synthesis of A9-Tetrahydrocannabinol from Natural Cannabidiol (Semisynthetic A9-THC)... 

Adams R, Baker BR, Structure of Cannabidiol. VII. A Method of Synthesis of a Tetrahydrocannabinol which Possesses Marihuana Activity, J Amer Chem Soc 62 2405-2408, 1940. 

Adams R, Pease DC, Cain CK, Baker BR, Clark JH, Wolff H, Wearn RB, Conversion of cannabidiol to a product with marihuana activity. A type reaction for synthesis of analogous substances. Conversion of cannabidiol to cannabinol, J Amer Chem Soc 62 2245—2246, 1940. 

Lander N. et al., Total synthesis of cannabidiol and deltal-tetrahydrocannabinol metabolites, J. Chem. Soc. (Perkin 1), 1, 8-16, 1976. 

For the synthesis of 6,12-dihydro-6-hydroxy-cannabidiol as the intermediate in accordance with the invention the starting materials are the readily available olivetol (formula II) and cis-p-menth-2-ene-l,8-diol (formula III). The reaction is performed in a suitable solvent, aromatic hydrocarbons such as benzene and toluene, halogenated hydrocarbons such as methylene chloride, chloroform, dichloroethane and trichloroethane, ethers such as diethylether, diisopropylether and tetrahydrofuran having proved to be suitable. Furthermore it is possible to use mixtures of the said solvents. Toluene, benzene, methylene chloride and chloroform are the preferred solvents for use in the method of the invention. 

Preparation of a s-cannabidiol by Minuti [72] was effected by the synthesis of 6a-cyano-tetrahydro-6H-benzo[c] chromen-6-ones 198 based on the Diels-Alder cycloaddition under high pressure of 3-cyano-coumarins 196 and 1,3-butadienes 197 (Scheme 48). Cycloadditions carried out at the atmospheric pressure gave the same adducts in significantly lower yields, but at the high temperature (150 °C). The cycloadduct 198a was subsequently converted to cis-cannabidiol in two reaction steps. 

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