Chemoenzymatic Synthesis of 5-Methylpsilocybin: A Tryptamine with Potential Psychedelic Activity
Janis Fricke, Alexander M. Sherwood, Adam L. Halberstadt, Robert B. Kargbo, Dirk Hoffmeister
Journal of Natural Products March 5, 2021 DOI: 10.1021/acs.jnatprod.1c00087 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical study Peer reviewed |
|---|---|
| Population | Mice |
| Intervention | 5-methylpsilocybin |
| Topics | Psilocybin |
| Keywords | Tryptamine Biological activity Biochemistry Hallucinogen Stereochemistry In vitro |
| Citations | 18 |
| Key points | 5-methylpsilocybin induced psychedelic-like activity in mice that was more potent than dimethyltryptamine but less potent than psilocybin. |
Abstract
A novel analogue of psilocybin was produced by hybrid chemoenzymatic synthesis in sufficient quantity to enable bioassay. Utilizing purified 4-hydroxytryptamine kinase from Psilocybe cubensis, chemically synthesized 5-methylpsilocin (2) was enzymatically phosphorylated to provide 5-methylpsilocybin (1). The zwitterionic product was isolated from the enzymatic step with high purity utilizing a solvent-antisolvent precipitation approach. Subsequently, 1 was tested for psychedelic-like activity using the mouse head-twitch response assay, which indicated activity that was more potent than the psychedelic dimethyltryptamine, but less potent than that of psilocybin.