P-Menth-2-ene

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. 

Photoreaction on (-i-) limonene (orange oil) produces mixed isomers, first couple of fractions canbe used to create active CBl agonists see Schenck 1964. cfs-p-Menth-2-ene-l,8,-diol and mixed isomers from a culture of Penicillium italicum andP digitatum (moldy oranges) see Bowen (1975). 

Cannabinoids.—New compounds (259 OH at C-8 or at C-10)847 and (259 OH at both C-9 and C-10)848 have been isolated from Cannabis sativa. p-Menth-2-ene-1,8-diol is an excellent synthon for the A9-tetrahydrocannabinol (THC) skeleton, coupling (ZnCl2-catalysed) with olivetol (3-n-pentylresorcinol) to form the (—)-parent compound, and forming the biologically potent 3-OH metabolite by appropriate modification of the reaction.849 The structurally equivalent substrate p-menth-1,8-dien-1 -ol reacted with other substituted resorcinols and led to A8- and A9-THC analogues differing in the side-chain attached at C-3.850-851 Use of the synthon (260) in a similar manner gave 2, 1 l-dihydroxy-A9-THC this was claimed... 

AscaiMole (l,4-epidioxy-p-menth-2-ene). CioHigOj, Mr 168.24, pale greenish-yellow, clear liquid, mp. 

Probably one of the best syntheses, developed at Johnson Matthey, starts with (+)-2-carene. In two steps (+)-p-menth-2-ene-l,8-diol is obtainable. The latter reacts with olivetol in presence of p-toluenesulfonic acid to form a crystalline solid, which is easily purified by recrystallisation. Ring closure is achieved with zinc bromide in surprisingly good yields. [139-141]... 

The yield may be further increased, if (+)-p-menth-2-ene-l,8-diol is esterified with diphenylacetic acid, although this requires a chromatographic step at the final stage. [142]... 

Spodptera litura converted (l/ )-irani-isolimonene (338) to (l/ ,4i )-p-menth-2-ene-8,9-diol (339) (Miyazawa et al., 1996b) (Figure 14.46). 

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