Chemoenzymatic Synthesis of 5-Methylpsilocybin: A Tryptamine with Potential Psychedelic Activity
Journal of Natural Products – March 05, 2021
Source: OpenAlex
Summary
A novel psilocybin analogue, 5-methylpsilocybin, exhibits potent biological activity. Its chemical synthesis involved a unique *in vitro* enzymatic phosphorylation of a tryptamine derivative, 5-methylpsilocin, utilizing a *Psilocybe cubensis* kinase. Biochemical analysis ensured high purity of this new hallucinogen. In drug studies, it showed psychedelic-like effects in mice, proving more potent than dimethyltryptamine but less potent than psilocybin. This innovative chemistry expands the realm of synthetic alkaloids.
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.