Synthesis of carbon-14 labeled ketamine and norketamine.
Lu Chen, Yong Gong, Rhys Salter
Journal of Labelled Compounds and Radiopharmaceuticals September 2018 DOI: 10.1002/jlcr.3669 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Peer reviewed |
|---|---|
| Topics | Esketamine Ketamine |
| Keywords | C-14 labeled Nmda receptors Noresketamine Norketamine Synthesis |
| Key points | C-14 labeled ketamine and norketamine were synthesized in five steps from [14C]CuCN, with the label at the quaternary carbon of the cyclohexyl ring, and their (S)- and (R)-enantiomers were separated by chiral resolution and chiral column separation. The labeled compounds are intended for assessing pharmacokinetic properties. |
Abstract
Ketamine is a well-known general anesthetic that inhibits cerebral NMDA receptors. Norketamine is a major circulating metabolite of this drug. A nasal spray formulation of esketamine, the S enantiomer of ketamine, is under development for the management of treatment-resistant depression. To assess the pharmacokinetic properties, C-14 labeled ketamine and norketamine were prepared separately from commercially available [14 C]CuCN through a five-step sequence with the C-14 label at the quaternary carbon of the cyclohexyl ring. Chiral resolution of [14 C]ketamine and chiral column separation of [14 C]norketamine resolved/separated the (S)-enantiomers from (R)-enantiomers.