Application of spin labeling to drug assays. III. [15N, 2H13]2,2,5,5‐tetramethylpyrroline‐1‐oxyl‐3‐carboxylic acid coupled to phenytoin

Yul Yost, Carl F. Polnaszek, Jordan L. Holtzman

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Phorone and [2H14]phorone were cyclized with 15NH3 or 15N2H3 to [15N]‐ or [15N, 2H17]‐4‐oxo‐2,2,6,6‐tetramethylpiperidine which were then brominated at C‐3 and C‐5. Ring contraction then gave 2,2,5,5‐tetramethylpyrroline‐3‐carboxamide, which with H2O2 gave the corresponding nitroxide. Hydrolysis in base of the doubly labeled nitroxide then gave [15N, 2H]2,2,5,5‐tetramethylpyrroline‐1‐oxyl‐3‐carboxylic acid. The latter, when coupled to phenytoin, afforded a spin‐labeled drug of high sensitivity for detection by ESR technique. If the synthesis was started with [2H14]phorone, negligible loss of deuterium was noted in the final product even when protiated reagents were used.

Original languageEnglish (US)
Pages (from-to)707-717
Number of pages11
JournalJournal of Labelled Compounds and Radiopharmaceuticals
Issue number6
StatePublished - Jun 1983


  • Pyrroline Nitroxides
  • Spin‐labeled Phenytoin
  • [N,H]Triacetonamine


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