Within this manuscript we describe a modular pathwayto synthesize biologically relevant (鈥?-trans-螖8-THCderivatives, which can be utilized to modulate the pharmacologically important CB1and CB2 receptors. This pathway includes a one-pot Friedel-Craftsalkylation/cyclization protocol, followed by Suzuki-Miyaura cross-couplingreactions and offers rise to a series of new 螖8-THC derivatives. Additionally, wedemonstrate making use of in depth NMR evidence that equivalent halide-substitutedFriedel-Crafts alkylation/cyclization items in earlier articles werewrongly assigned as the para-isomers, which also has consequence for theassignment of the subsequent cross-coupled items and interpretation of theirbiological activity. Considering the importance on the availabilityof THC derivatives in medicinal chemistry research as well as the fact that previouslysynthesized compounds were wrongly assigned, we feel this study is describing astraightforward pathway into new cannabinoids. (R)-1-(4-Methoxyphenyl)ethanol Formula 3-(3-Butyn-1-yl)-3H-diazirine-3-ethanol web PMID:24140575