Hybromet: A Ligand for Purifying Opioid Receptors

Condensation of the Grignard reagent derive from 2[4-(allyloxy)phenyl]ethyl bromide (4b) with 7α-acetyl-6,14-endo-ethenotetrahydrothebaine (5) furnished the (R) tertiary carbinol, 7, which upon methoxymercuration followed by treatment with the KBr gave the bromomercurio compound 10 (Hybromet). The corresponding N-cyclo-propylmethyl analogue, 11, was prepared also. The bromomercurio compound, 1, and the mercaptobenzothiazole derivative, 3, gave allyl phenyl ether when treated with BAL at room temperature. Similar treatment of 10 with BAL gave 7 in high yield. Binding studies using rat brain homogenates indicated that 7, 13, and 14 have moderately high affinities for μ rather than δ binding sites. Although much weaker, 10 showed preferential μ binding also. These results along with the fact that 10 reacted smoothly with sulfhydryl groups suggest that Hybromet would be a suitable ligand for use in affinity chromatography.