58434-44-9Relevant academic research and scientific papers
3'-Hydroxy- and (±)-3',11-dihydroxy-Δ9-tetrahydrocannabinol: Biologically active metabolites of Δ9-tetrahydrocannabinol
Handrick,Duffley,Lambert,et al.
, p. 1447 - 1450 (2007/10/02)
Synthesis of 3'-Hydroxy- (7) and (±)-3',11-dihydroxy-Δ9-tetrahydrocannabinol (11), metabolites of Δ9-THC, is described. Condensation of the monoterpene (±)-cis-p-menth-2-ene-1,8-diol (1) and (±)-3'-acetoxyolivetol (2) in the presence of fused ZnCl2 in CH2Cl2 gave a mixture from which the Δ9-THC derivative 3, containing small amounts of the Δ8 isomer 4, was isolated after column chromatography. This mixture was separated as their diacetates 5 and 6 by high-pressure liquid chromatography. Alkaline hydrolysis (5% KOH in MeOH) of 5 furnished the metabolite 7. Condensation of (±)-8 with 2 in the presence of p-toluenesulfonic acid gave 9a, which was acetylated to 9b. Treatment with HgO/BF3.Et2O in wet THF gave the aldehyde 10. Reduction with LiAlH4 furnished the metabolite 11. These metabolites were compared with Δ9-THC for their ability to depress spontaneous activity and rectal temperature in mice and for their effects on overt behavior in dogs. 3'-Hydroxy-Δ9-THC was also compared to Δ9-THC in the mouse sympatomatology test and cardiovascular system in dogs. The metabolites produced pharmacological effects similar to those of Δ9-THC in all tests. 3'-Hydroxy-Δ9-THC was 2-3 times more effective than Δ9-THC in the behavioral tests, whereas (±)-3',11-dihydroxy-Δ9-THC was approximately 3 times less active than Δ9-THC.
