Journal of Natural Products
September 20, 2017
Claudius Lenz, Jonas Wick, Dirk Hoffmeister
62 citations
A previously unreported natural compound, ω-N-methyl-4-hydroxytryptamine (norpsilocin), was identified in the fruiting bodies of the hallucinogenic mushroom Psilocybe cubensis. Its structure was determined using NMR spectroscopy and high-resolution mass spectrometry. Norpsilocin is likely the actual psychoactive agent released from its phosphate ester derivative, the known natural product baeocystin. The authors also developed a simple extraction method that avoids dephosphorylation, thereby preserving the natural metabolic profile of Psilocybe mushrooms for analysis.
Angewandte Chemie International Edition
November 14, 2019
Claudius Lenz, Jonas Wick, Daniel Braga et al.
56 citations
When psilocybin-producing mushrooms are injured, they turn blue due to a two-step enzymatic cascade. The phosphatase PsiP removes a phosphate group from psilocybin to yield psilocin, and the enzyme PsiL oxidizes psilocin's 4-hydroxy group. This oxidation triggers the formation of blue oligomers, primarily linked at carbon-5, as shown by carbon-13 NMR. Mass and infrared spectroscopy reveal a mixture of psilocyl chains ranging from 3 to 13 units long, with multiple pathways depending on oxidant strength and substrate concentration. The findings suggest that psilocybin's phosphate group acts as a reversible protective modification, preventing premature bluing until injury occurs.
Chemistry - A European Journal
July 16, 2018
Janis Fricke, Claudius Lenz, Jonas Wick et al.
52 citations
Psilocybin, the prodrug to the psychotropic compound psilocin, is biosynthesized by numerous mushroom species in the fungal genus Psilocybe and other genera, colloquially known as 'magic mushrooms' for their hallucinogenic effects and recreational use. Clinical trials have recognized psilocybin as a valuable candidate for development into a medication against depression and anxiety. This review highlights the recently elucidated biosynthesis of psilocybin, the concurrently developed concept of enzymatic in vitro and heterologous in vivo production, along with previous synthetic routes. The prospect of psilocybin as a promising therapeutic may entail increased demand, which can be met by biotechnological production. The review also briefly touches on psilocybin's therapeutic relevance and pharmacology.
Chemistry - A European Journal
February 26, 2020
Janis Fricke, Robert B. Kargbo, Lars Regestein et al.
48 citations
Psilocybin, the main psychoactive alkaloid in Psilocybe mushrooms, is being tested as a treatment for depression. Pharmaceutical psilocybin is currently made by synthetic chemistry. Replacing a difficult chemical phosphorylation step with the mushroom enzyme PsiK allowed production of one gram of psilocybin from psilocin in 20 minutes. A pilot-scale protocol also yielded 150 mg of active, soluble PsiK enzyme. This combination of tryptamine chemistry and enzymatic catalysis may provide access to psilocybin at potentially lower cost.
ChemPlusChem
October 1, 2020
Claudius Lenz, Alexander M. Sherwood, Robert B. Kargbo et al.
40 citations
Psilocybe fungi, known as magic mushrooms, produce psilocybin from the amino acid L-tryptophan. Recent research shows these fungi have a more varied secondary metabolism derived from this amino acid. This review describes psilocybin and related compounds, including blue-colored psilocyl oligomers, beta-carbolines, and N,N-dimethyl-L-tryptophan, along with current knowledge of their biosynthesis. The work covers pharmacological, medicinal, ecological, biochemical, and evolutionary aspects of these natural products.
ChemBioChem
April 28, 2022
Claudius Lenz, Sebastian Dörner, Felix Trottmann et al.
26 citations
Psilocybin, the main alkaloid in psychedelic mushrooms, acts as a prodrug to psilocin, a potent psychedelic that alters human consciousness. Its positional isomer bufotenin differs in reported pharmacology. Experiments tested whether psilocin's C-4 hydroxy group influences properties through pseudo-ring formation via an intramolecular hydrogen bond (IMHB). NMR spectroscopy and quantum chemical calculations compared hydrogen bond behavior in 4- and 5-hydroxylated tryptamines. Evidence shows a pseudo-ring in psilocin and that sidechain/hydroxyl interactions affect oxidation kinetics. The propensity to form IMHBs leads to more uncharged species that cross the blood-brain barrier, unlike bufotenin. This helps explain psilocin's pharmacology and supports developing psilocybin as a therapy for major depressive disorder.
Chemistry - A European Journal
June 1, 2021
Claudius Lenz, Sebastian Dörner, Alexander Sherwood et al.
19 citations
Psilocin, the psychoactive compound derived from psilocybin, turns blue when mushrooms containing it are bruised. This blue color was previously thought to come from a specific chemical dimer (5,5'-coupled quinone). By synthesizing stable, ring-methylated derivatives of psilocin and analyzing their oxidized forms with spectroscopy and computational modeling, researchers showed that the blue color actually arises from a different dimer (7,7'-coupled quinoid). The original hypothesis was not supported.