Synthesis of Cannabinoid Model Compounds. Part 3 . (6a R , 10a R )‐ N ‐ethyl‐Δ 8 ‐tetrahydrocannabinol‐18‐amide, (6a R , 10a R , 17 RS )‐ N ‐ethyl‐17‐methyl‐Δ 8 ‐ tetrahydrocannabinol‐18‐amide and (6a R , 10a R )‐17,18‐didehydro‐Δ 8 ‐tetrahydrocannabinol

The novel cannabinoids (6a R , 10a R )‐ N ‐ethyl‐Δ 8 ‐tetrahydrocannabinol‐18‐amide (15) and (6a R , 10a R , 17 RS )‐ N ‐ethyl‐17‐methyl‐Δ 8 ‐ tetrahydrocannabinol‐18‐amide (16) , designed as cannabinoid affinity ligands, were synthesized from the corresponding acids 11 and 12 via the N ‐hydroxysuccinimide esters. Amide 16 was tested in the rat and was generalized to Δ 9 ‐tetrahydrocannabinol, being 5 times less potent than the training drug. An improved synthesis of (6a R , 10a R )‐17,18‐didehydro‐Δ 8 ‐tetrahydrocannabinol (23) is reported. As model reaction for the preparation of a tritiated Δ 8 ‐tetrahydrocannabinol, compound 23 was selectively deuterated at C(17) and C(18) in benzene/Et 3 N using [(C 6 H 5 ) 3 P] 3 RuCl 2 as catalyst.