Howard L. Hunter Laboratory, Clemson University, Clemson, SC 29634-0973, United States.
Bioorg Med Chem. 2010 Nov 15;18(22):7809-15. doi: 10.1016/j.bmc.2010.09.061. Epub 2010 Sep 29.
Δ(8)-Tetrahydrocannabinol (26), 3-(1',1'-dimethylbutyl)- (12), 3-(1',1'-dimethylpentyl)- (13), 3-(1',1'-dimethylhexyl)- (14) and 3-(1',1'-dimethylheptyl)-Δ(8)-tetrahydrocannabinol (15) have been converted into the corresponding 1-bromo-1-deoxy-Δ(8)-tetrahydrocannabinols (25, 8-11). This was accomplished using a protocol developed in our laboratory in which the trifluoromethanesulfonate of a phenol undergoes palladium mediated coupling with pinacolborane. Reaction of this dioxaborolane with aqueous-methanolic copper(II) bromide provides the aryl bromide. The affinities of these bromo cannabinoids for the cannabinoid CB(1) and CB(2) receptors were determined. All of these compounds showed selectivity for the CB(2) receptor and one of them, 1-bromo-1-deoxy-3-(1',1'-dimethylhexyl)-Δ(8)-tetrahydrocannabinol (10), exhibits 52-fold selectivity for this receptor with good (28nM) affinity.
Δ(8)-四氢大麻醇（26）、3-(1',1'-二甲基丁基)- (12）、3-(1',1'-二甲基戊基)- (13）、3-(1',1'-二甲基己基)- (14）和 3-(1',1'-二甲基庚基)-Δ(8)-四氢大麻醇（15）已转化为相应的 1-溴-1-脱氧-Δ(8)-四氢大麻醇（25、8-11）。这是使用我们实验室开发的方案完成的，其中酚的三氟甲磺酸酯通过钯介导与频哪醇硼烷偶联。该二氧硼烷与水-甲醇铜(II)溴化物反应得到芳基溴化物。这些溴代大麻素对大麻素 CB(1)和 CB(2)受体的亲和力进行了测定。所有这些化合物都显示出对 CB(2)受体的选择性，其中一种化合物 1-溴-1-脱氧-3-(1',1'-二甲基己基)-Δ(8)-四氢大麻醇（10）对该受体具有 52 倍的选择性，亲和力良好（28nM）。
