Synthesis and characterization of optically pure [3H](+)-azidophenazocine ([3H](+)-AZPH), a novel photoaffinity label for sigma receptors

[3H](+)-cis-N-(2-(4-Azidophenyl)ethyl)-2'-hydroxy-2,6-dimethyl-6,7-benzomorphan [3H]1) ([3H](+)-AZPH), a novel high affinity and high selectivity benzomorphan based photoaffinity label for sigma receptors was synthesized in 4 steps starting with optically pure (+)-normetazocine and 2-(p-azidophenyl)ethyl methanesulfonate ester. Condensation of these compounds in DMF in the presence of NaHCO3 afforded 1 in 77% yield. The tritiation precursor (+)-cis-N-(2-(4-azidophenyl)ethyl-2'-hydroxy-1',3'-dibromo-2,6-dimethyl-6,7-benzomorphan (4) for medium specific activity [3H]1 was obtained in 96% yield by bromination of 1 with 2 equivalents of bromine. The sequence of catalytic tritiation of 4, treatment of the resulting aniline ([3H]5) (13.5% radiochemical yield, specific activity 22.9 Ci/mmol) with nitrous acid followed by sodium azide afforded the target compound in 78% chemical yield. (author)