1451-20-3Relevant academic research and scientific papers
High-pressure diels-alder cycloadditions between benzylideneacetones and 1,3-Butadienes: Application to the synthesis of (R,R)-(-)- and (S,S)-(+)-Δ8-tetrahydrocannabinol
Ballerini, Eleonora,Minuti, Lucio,Piermatti, Oriana
supporting information; experimental part, p. 4251 - 4260 (2010/09/05)
High-pressure Diels-Alder reactions of various alkoxy/alkyl-substituted benzylideneacetones with methyl-1,3-butadienes are reported. Activation by high pressure (8-11 kbar) in combination with the mild Lewis acid HfCl 42THF allows these reactions to efficiently and regioselectively produce a series of ortho-substituted cyclohexenyl-benzene cycloadducts, that are useful precursors for the expeditious construction of the privileged 6,6-dimethyltetrahydro-6H-benzo[c]chromene skeleton. Application to the synthesis of Δ8-trans-THC in both enantiomeric pure forms is based on the successful resolution of selected cycloadduct by the SAMP-hydrazone method.
Synthesis and pharmacological evaluation of ether and related analogues of Δ8-, Δ9-, and Δ9,11-tetrahydrocannabinol
Compton,Prescott Jr.,Martin,Siegel,Gordon,Razdan
, p. 3310 - 3316 (2007/10/02)
The primary goal of this research was to synthesize a series of ether analogues of the cannabinoid drug class and to evaluate their agonist and antagonist pharmacological properties in either the mouse or the rat. Agonist and antagonist activity was evaluated in mice using a multiple-evaluation procedure (locomotor activity, tail-flick latency, hypothermia, ring immobility) and activity in rats determined in a discriminative stimulus paradigm. Additionally, novel analogues were evaluated for their ability to bind to the THC receptor site labeled by 3H-CP-55,940. None of the cannabinoid analogues were capable of attenuating the effects of Δ9-THC (3 mg/kg) in either the rat (doses up to 10 mg/kg) or in the mouse (doses up to 30 mg/kg). It also appears that the compounds with minimal in vivo activity are not mixed agonist/antagonists. These data would suggest that the phenolic hydroxyl is important for receptor recognition (binding) and in vivo potency. Additionally, cannabinoid methyl ethers previously considered inactive have been found to produce limited activity. Lastly, data suggest that Δ9,11- THC is more potent than previous reports indicated, and does possess pharmacological activity.
