Chlorinated phenyl azides as photolabeling reagents. Synthesis of an ortho,ortho'-dichlorinated arylazido PCP receptor ligand.
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).
Cai
S X
SX
Department of Chemistry, University of Oregon, Eugene 97403.
Glenn
D J
DJ
Gee
K R
KR
Yan
M
M
Cotter
R E
RE
Reddy
N L
NL
Weber
E
E
Keana
J F
JF
D000345:Affinity Labels / Q000138:chemical synthesis* / Q000378:metabolism; D000818:Animals; D001386:Azides / Q000138:chemical synthesis*; D002490:Central Nervous System / Q000648:ultrastructure; D006843:Hydrocarbons, Chlorinated / Q000138:chemical synthesis*; D008024:Ligands; D017478:Receptors, Phencyclidine / Q000378:metabolism*
D000345:Affinity Labels; D001386:Azides; D006843:Hydrocarbons, Chlorinated; D008024:Ligands; D017478:Receptors, Phencyclidine