Chlorinated phenyl azides as photolabeling reagents. Synthesis of an ortho,ortho'-dichlorinated arylazido PCP receptor ligand

• Published in: Bioconjugate chemistry 1993-11, Vol.4 (6), p.545-548
• Main Authors: Cai, Sui Xiong, Glenn, Denis J, Gee, Kyle R, Yan, Mingdi, Cotter, Ronald E, Reddy, N. Laxma, Weber, Eckard, Keana, John F. W
• Format: Article
• Language: English
• Subjects: Affinity Labels - chemical synthesis; Affinity Labels - metabolism; Animals; Azides - chemical synthesis; Biological and medical sciences; Central Nervous System - ultrastructure; Fundamental and applied biological sciences. Psychology; Hydrocarbons, Chlorinated - chemical synthesis; Ligands; Miscellaneous; Molecular biophysics; Radiation-biomolecule interaction; Receptors, Phencyclidine - metabolism
• ISSN: 1043-1802; 1520-4812
• DOI: 10.1021/bc00024a018

The enhanced photolabeling properties of chlorinated phenyl azides are demonstrated by the synthesis and photolysis of methyl 4-azido-2,3,5,6-tetrachlorobenzoate (3) and methyl 4-azido-3,5-dichlorobenzoate (4). Photolysis of azide 3 in 1 M diethylamine/cyclohexane as the trapping medium gave 34% NH-insertion product. Similar photolysis of azide 4 gave 35% NH insertion product. These results demonstrate that chlorinated phenyl azides are significantly better at undergoing NH insertion than nonhalogenated analogs and suggest that improvement of existing aryl azide-based photolabels might be achieved by introduction of chlorine atoms on either side of the azide group. As an application, 3-azido-2,4-dichloro-10,5-(iminomethano)-10,11-dihydro-5H- dibenzo[a,d]cycloheptene (19), an analog of the potent PCP receptor ligand IDDC (14), was synthesized and its affinity for the PCP receptor was determined to be 6.3 +/- 0.7 microM (IC50 against [3H]MK801).