Metabolism of Cannabis. XI. Synthesis of Delta7-Tetrahydrocannabinol and 7-Hydroxytetrahydrocannabinol.

Importance of the C-1 Substituent in Classical Cannabinoids to CB2 Receptor Selectivity: Synthesis and Characterization of a Series of O,2-Propano-Δ8-tetrahydrocannabinol Analogs

“…The second route provided the cannabinoids 8−10a,b , in addition to 4 , as outlined in Scheme . The desired 8 was obtained in 33% chromatographed yield by photochemical isomerization of 1 similar to that reported for Δ , -THC . Oxidative cleavage of the impure olefin 8 with potassium permanganate/sodium periodate gave O ,2-propano-9-oxo-11-nor-HHC ( 9 ) in 9−13% chromatographed yield in contrast with the 91% yield obtained with Δ 9,11 -THC methyl ether…”

“…Results reported here for a series of C-9 analogs of the cyclic ether O,2propano-∆ 8 -tetrahydrocannabinol (O,2-propano-∆ 8 -THC) point to the C-1 position in classical cannabinoids as a position for which CB 2 subtype selectivity occurs within the cannabinoid receptors. O,2-Propano-11-nor-∆ 8 -THC, O,2-propano-∆ 9,11 -THC, O,2-propano-9-oxo-11-norhexahydrocannabinol (O,2-propano-9-oxo-11-nor-HHC), and O,2-propano-9R-and O,2-propano-9β-OH-11-nor-HHC were synthesized and evaluated in radioligand displacement assays for affinity at the CB 1 and CB 2 receptors and in the mouse vas deferens in vitro assay and the mouse tetrad in vivo assay for cannabinoid activity. Evaluation of binding affinity at the CB 1 and CB 2 receptors revealed that each compound possesses a modest increased affinity for the CB 2 receptor.…”

“…This inhibition could readily be prevented by the selective CB 1 cannabinoid receptor antagonist SR-141716A. The analogs exhibited unique in vivo profiles with O,2-propano-∆ 9,11 -THC exhibiting antinociception with reduced activity in three other in vivo measures and O,2-propano-9β-OH-HHC exhibiting lack of dose responsiveness in all measures. The CB 2 selectivities of the O,2-propano analogs may be due to differences in solvation/desolvation that occur when the ligands enter the CB 1 vs CB 2 binding site.…”

Metabolic Transformation of (3R, 4R)‐Δ1(7)‐Tetrahydrocannabinol by a Rat Liver Microsomal Preparation

“…Based on these structures, a new rule for mass spectroscopic fragmentation of cannabinoids is presented. [9] by photoisomerisation of (3R,4R)-LI'(~)-THC (2), was incubated with an enriched rat liver microsomal preparation [lo] from 34 male Whistar rats (250-300 8). After 2 h at 37" the incubation mixtures were extracted with ether.…”

4,9-Methano[11]annulenylidene. Example of a ten-.pi.-electron carbocyclic aromatic carbene

“…In the absence of substrate, a hydrocarbon was formed (67%), which showed all of the properties expected for the fulvalene 4. The infrared showed a (OCH3) at 6.12 and 6.28, doublets (cyclopropyl H) at 6.98 and 7.28 (J = 6.0 Hz), and one methylene proton at 9.84 (J = 12.0 Hz). Double irradiation experi-ments15 showed the other methylene proton to be located at 6.28.…”