Robertson L R, Duffley R P, Razdan R K, Martin B R, Harris L S, Dewey W L
J Med Chem. 1984 Apr;27(4):550-2. doi: 10.1021/jm00370a023.
Several 9-substituted delta 8-tetrahydrocannabinol (delta 8-THC) analogues were synthesized and evaluated for biological activity in mice. Compounds with phenyl (2b) and butyl (2c) substituents were prepared by the addition of phenyllithium and n-butyllithium, respectively, to (-)-9-nor-9-oxohexahydrocannabinol (1), followed by dehydration, whereas, isopropyl (2d), PhCH2 (2e), and Ph(CH2)2 (2f) derivatives were synthesized via the Grignard reaction with subsequent dehydration. Compounds with C2H5CH(OH) (2g) and CH3CH(OH) (2h) substituents at C-9 were prepared from (-)-9-nor-9-formyl-delta 8-tetrahydrocannabinol acetate (3) by the reaction of ethyl and methyl Grignard reagents, respectively. Biological activity indicated that a methyl group at the C-9 position is, thus far, optimum for producing hypoactivity and hypothermia in mice. In addition, hydroxyethyl substitution at position 9 reduced and antinociceptive activity of delta 8-THC, in contrast to the increased activity reported for hydroxymethyl substitution.
合成了几种9-取代的δ8-四氢大麻酚（δ8-THC）类似物，并在小鼠中评估了其生物活性。分别通过将苯基锂和正丁基锂加成到（-）-9-去甲-9-氧代六氢大麻酚（1）上，然后脱水，制备了具有苯基（2b）和丁基（2c）取代基的化合物，而异丙基（2d）、苄基（2e）和苯乙基（2f）衍生物则通过格氏反应并随后脱水合成。在C-9位具有C2H5CH(OH)（2g）和CH3CH(OH)（2h）取代基的化合物分别由（-）-9-去甲-9-甲酰基-δ8-四氢大麻酚乙酸酯（3）与乙基和甲基格氏试剂反应制备。生物活性表明，到目前为止，C-9位的甲基对于在小鼠中产生活动减退和体温过低是最佳的。此外，与报道的羟甲基取代活性增加相反，9位的羟乙基取代降低了δ8-THC的抗伤害感受活性。
