Synthesis of Cannabinoid Model Compounds. Part 3. (6aR, 10aR)‐N‐ethyl‐Δ8‐tetrahydrocannabinol‐18‐amide, (6aR, 10aR, 17 RS)‐N‐ethyl‐17‐methyl‐Δ8‐ tetrahydrocannabinol‐18‐amide and (6aR, 10aR)‐17,18‐didehydro‐Δ8‐tetrahydrocannabinol

The novel cannabinoids (6aR, 10aR)-N-ethyl-Δ8-tetrahydrocannabinol-18-amide (15) and (6aR, 10aR, 17 RS)-N-ethyl-17-methyl-Δ8- tetrahydrocannabinol-18-amide (16), designed as cannabinoid affinity ligands, were synthesized from the corresponding acids 11 and 12via the N-hydroxysuccinimide esters. Amide 16 was tested in the rat and was generalized to Δ9-tetrahydrocannabinol, being 5 times less potent than the training drug. An improved synthesis of (6aR, 10aR)-17,18-didehydro-Δ8-tetrahydrocannabinol (23) is reported. As model reaction for the preparation of a tritiated Δ8-tetrahydrocannabinol, compound 23 was selectively deuterated at C(17) and C(18) in benzene/Et3N using [(C6H5)3P]3RuCl2 as catalyst.