Identification of ω-N-Methyl-4-hydroxytryptamine (Norpsilocin) as a Psilocybe Natural Product

Abstract

We report the identification of ω-N-methyl-4-hydroxytryptamine (norpsilocin, 1) from the carpophores of the hallucinogenic mushroom Psilocybe cubensis. The structure was elucidated by 1D and 2D NMR spectroscopy and high-resolution mass spectrometry. Norpsilocin has not previously been reported as a natural product. It likely represents the actual psychotropic agent liberated from its 4-phosphate ester derivative, the known natural product baeocystin. We further present a simple and artifact-free extraction method that prevents dephosphorylation and therefore helps reflect the naturally occurring metabolic profile of Psilocybe mushrooms in subsequent analyses.

S‐Adenosyl‐l‐Methionine Salvage Impacts Psilocybin Formation in “Magic” Mushrooms

“…For submerse cultures, the fungus was incubated in MEP liquid medium for 4 days at 25 °C and 140 rpm. Carpophore formation was induced as described . Mycelia were collected, shock‐frozen in liquid nitrogen and lyophilized prior to RNA isolation or metabolite quantification.…”

Bis(4-hydroxy-N-isopropyl-N-methyltryptammonium) fumarate: a new crystalline form of miprocin

“…Psilocybin is one of at least ten psychoactive tryptamines present in 'magic' mushrooms, with natural psilocybin analogs being identified as recently as 2019 (Lenz et al, 2017;Blei et al, 2020). Variations in the three-dimensional structure of these natural analogs (as well as synthetic analogs) correlate with differences in their cellular and clinical pharmacology through their structure-activity relationship (SAR) (Nichols, 2018).…”

Production Options for Psilocybin: Making of the Magic

“…Subsequently, close to 200 species, in the above genera and in Gymnopilus , Pluteus , and Inocybe species, have been confirmed as producers of 1 . The content of 1 depends on the extraction and workup method, as it may decompose to 2 . Reported values are typically about 0.85 % of the dry mass for Psilocybe serbica , approximately 1.0 % for P. semilanceata , and around 1.5–1.8 % in P. azurescens…”

“…The specificity of PsiM is remarkable. Aside from mere trace amounts of product 5 , detected with 13 as a methyl acceptor, PsiM seems to require a 4‐ O ‐phosphoryloxy group for proper substrate recognition.…”

“…Hence, the pathway is designed to prevent, rather than support, the formation of 2 . Still, 2 has been reported from Psilocybe species, yet the reported quantities represent an artifact generated during workup …”