Cannabinoids and other Phenolic Monoterpenoids

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 

Bucourt s method for estimation of torsional strain can be successfully applied to the THC ring system to give a surprisingly good quantitative estimate of the relative stability of the various double-bond isomers, in particular of the position of equilibrium for A8 A9 for the parent and model compounds demethylated at C-6.867 

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