Hybromet: a ligand for purifying opioid receptors

• Published in: Journal of medicinal chemistry Vol. 28; no. 12; pp. 1950 - 1953
• Main Authors: Archer, Sydney, Michael, Josephine, Osei-Gyimah, Peter, Seyed-Mozaffari, Ahmad, Zukin, R. Suzanne, Maneckjee, Rhoda, Simon, Eric J, Gioannini, Theresa L
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 01.12.1985
• Subjects: Animals; Binding Sites; Brain - metabolism; Chemical Phenomena; Chemistry; Chromatography, Affinity; Exact sciences and technology; Heterocyclic compounds; Heterocyclic compounds with n hetero atom and also o and/or s, se, te hetero atoms; Indicators and Reagents; Ligands; Naltrexone - metabolism; Organic chemistry; Organomercury Compounds - chemical synthesis; Organomercury Compounds - metabolism; Preparations and properties; Rats; Receptors, Opioid - isolation & purification; Receptors, Opioid - metabolism; Thebaine - analogs & derivatives; Thebaine - chemical synthesis; Thebaine - metabolism; Polycyclic compound; Model reaction; Magnesium Organic compounds; Ether; Allylic compound; Oxygen nitrogen heterocycle
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm00150a032

Condensation of the Grignard reagent derive from 2-[4-(allyloxy)phenyl]ethyl bromide (4b) with 7 alpha-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-cyclopropylmethyl 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 mu rather than delta binding sites. Although much weaker, 10 showed preferential mu 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.