Stevens CL,
*,
Klundt IL,
Munk ME,
Pillai MD.
Wayne State University, Detroit, USA
Amino Ketone Rearrangements. IV. Thermal Rearrangements of α-Amino Methyl Ketones.
J. Org. Chem. 1965;
30: 2967-2972
DOI:
10.1021/jo01020a019
Key words
ketamines - anesthetic drug - rearrangement
Significance
Ketamine is an anesthetic drug used both in human and veterinary medicine. It acts primarily as a noncompetitive antagonist of the NMDA receptor, but also shows an activating effect on AMPA receptors. Besides its use as a sedative or pain management drug, ketamine has been shown to be a potent short-acting antidepressant. It induces effects similar to phencyclidine (PCP) with reduced behavioral toxicity.
Comment
The key methodology for the synthesis of ketamine is a thermal rearrangement of α-hydroxy imines to α-amino ketones. This was developed by Stevens and co-workers, who also reported on a series of analogs in a patent (US patent 3254124), which included ketamine. Although synthesized as a racemic mixture, the two enantiomers have remarkably different pharmacologies, with (S)-ketamine being a more potent anesthetic and (R)-ketamine being a more potent antidepressant.
