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 via OpenAlex
Summary
AI-generated from the abstractA novel analogue of psilocybin, 5-methylpsilocybin, was produced through a hybrid chemoenzymatic synthesis, combining chemical synthesis of 5-methylpsilocin with enzymatic phosphorylation using a purified kinase from Psilocybe cubensis. The product was isolated with high purity via solvent-antisolvent precipitation. In a mouse head-twitch response assay, 5-methylpsilocybin showed psychedelic-like activity more potent than dimethyltryptamine but less potent than psilocybin.
Study at a glance
| Characteristics | Preclinical study Peer reviewed |
|---|---|
| Population | Mice |
| Intervention | 5-methylpsilocybin |
| Topics | Psilocybin |
| Keywords | Tryptamine Biological activity Biochemistry Hallucinogen |
| Citations | 18 |
| Key finding | 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.