ACS Publications. Most Trusted. Most Cited. Most Read
Identification of ω-N-Methyl-4-hydroxytryptamine (Norpsilocin) as a Psilocybe Natural Product
My Activity
    Note

    Identification of ω-N-Methyl-4-hydroxytryptamine (Norpsilocin) as a Psilocybe Natural Product
    Click to copy article linkArticle link copied!

    View Author Information
    Department of Pharmaceutical Microbiology at the Hans-Knöll-Institute, Friedrich-Schiller-Universität Jena, Winzerlaer Strasse 2, 07745 Jena, Germany
    *Phone: +49 3641 949850. Fax: +49 3641 949852. E-mail: [email protected]
    Other Access OptionsSupporting Information (1)

    Journal of Natural Products

    Cite this: J. Nat. Prod. 2017, 80, 10, 2835–2838
    Click to copy citationCitation copied!
    https://doi.org/10.1021/acs.jnatprod.7b00407
    Published September 20, 2017
    Copyright © 2017 The American Chemical Society and American Society of Pharmacognosy

    Abstract

    Click to copy section linkSection link copied!
    Abstract Image

    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.

    Copyright © 2017 The American Chemical Society and American Society of Pharmacognosy

    Read this article

    To access this article, please review the available access options below.

    Get instant access

    Purchase Access

    Read this article for 48 hours. Check out below using your ACS ID or as a guest.

    Recommended

    Access through Your Institution

    You may have access to this article through your institution.

    Your institution does not have access to this content. Add or change your institution or let them know you’d like them to include access.

    Supporting Information

    Click to copy section linkSection link copied!

    The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.jnatprod.7b00407.

    • 1D and 2D NMR spectra of norpsilocin (1) (PDF)

    Terms & Conditions

    Most electronic Supporting Information files are available without a subscription to ACS Web Editions. Such files may be downloaded by article for research use (if there is a public use license linked to the relevant article, that license may permit other uses). Permission may be obtained from ACS for other uses through requests via the RightsLink permission system: http://pubs.acs.org/page/copyright/permissions.html.

    Cited By

    Click to copy section linkSection link copied!
    Citation Statements
    Explore this article's citation statements on scite.ai

    This article is cited by 40 publications.

    1. Grant C. Glatfelter, Eline Pottie, John S. Partilla, Alexander M. Sherwood, Kristi Kaylo, Duyen N. K. Pham, Marilyn Naeem, Vamshikrishna Reddy Sammeta, Stacie DeBoer, James A. Golen, Elliott B. Hulley, Christophe P. Stove, Andrew R. Chadeayne, David R. Manke, Michael H. Baumann. Structure–Activity Relationships for Psilocybin, Baeocystin, Aeruginascin, and Related Analogues to Produce Pharmacological Effects in Mice. ACS Pharmacology & Translational Science 2022, 5 (11) , 1181-1196. https://doi.org/10.1021/acsptsci.2c00177
    2. Grant C. Glatfelter, Duyen N. K. Pham, Donna Walther, James A. Golen, Andrew R. Chadeayne, Michael H. Baumann, David R. Manke. Synthesis, Structural Characterization, and Pharmacological Activity of Novel Quaternary Salts of 4-Substituted Tryptamines. ACS Omega 2022, 7 (28) , 24888-24894. https://doi.org/10.1021/acsomega.2c03476
    3. Andrew R. Chadeayne, Duyen N. K. Pham, Brian G. Reid, James A. Golen, David R. Manke. Active Metabolite of Aeruginascin (4-Hydroxy-N,N,N-trimethyltryptamine): Synthesis, Structure, and Serotonergic Binding Affinity. ACS Omega 2020, 5 (27) , 16940-16943. https://doi.org/10.1021/acsomega.0c02208
    4. Alexander M. Sherwood, Adam L. Halberstadt, Adam K. Klein, John D. McCorvy, Kristi W. Kaylo, Robert B. Kargbo, Poncho Meisenheimer. Synthesis and Biological Evaluation of Tryptamines Found in Hallucinogenic Mushrooms: Norbaeocystin, Baeocystin, Norpsilocin, and Aeruginascin. Journal of Natural Products 2020, 83 (2) , 461-467. https://doi.org/10.1021/acs.jnatprod.9b01061
    5. Shuo Yuan, Dan-Qing Zhang, Jing-Ya Zhang, Bin Yu, Hong-Min Liu. Palladium-Catalyzed Ligand-Free Double Cyclization Reactions for the Synthesis of 3-(1′-Indolyl)-phthalides. Organic Letters 2020, 22 (3) , 814-817. https://doi.org/10.1021/acs.orglett.9b04241
    6. Jonathan Cohen, Liron Sulimani, Shiri Procaccia, Yaniv Lerenthal, Looz Milay, Ido Taran, Anna Shapira, David Meiri. Comprehensive analysis of 42 psilocybin-producing fungal strains reveals metabolite diversity and species-specific clusters. Scientific Reports 2025, 15 (1) https://doi.org/10.1038/s41598-025-97710-z
    7. Sebastian Dörner, Felix Trottmann, Paul M. Jordan, Kai Rogge, Benjamin Bartels, Oliver Werz, Christian Hertweck, Dirk Hoffmeister. Das tödliche Pilzgift Muscarin wird bei Zellverletzung aus einem harmlosen phosphorylierten Vorläufer freigesetzt. Angewandte Chemie 2024, 136 (52) https://doi.org/10.1002/ange.202417220
    8. Sebastian Dörner, Felix Trottmann, Paul M. Jordan, Kai Rogge, Benjamin Bartels, Oliver Werz, Christian Hertweck, Dirk Hoffmeister. The Fatal Mushroom Neurotoxin Muscarine is Released from a Harmless Phosphorylated Precursor upon Cellular Injury. Angewandte Chemie International Edition 2024, 63 (52) https://doi.org/10.1002/anie.202417220
    9. Paula Sophie Seibold, Sebastian Dörner, Janis Fricke, Tim Schäfer, Christine Beemelmanns, Dirk Hoffmeister. Genetic regulation of l-tryptophan metabolism in Psilocybe mexicana supports psilocybin biosynthesis. Fungal Biology and Biotechnology 2024, 11 (1) https://doi.org/10.1186/s40694-024-00173-6
    10. Orr Shahar, Alexander Botvinnik, Amit Shwartz, Elad Lerer, Peretz Golding, Alex Buko, Ethan Hamid, Dani Kahn, Miles Guralnick, Karin Blakolmer, Gilly Wolf, Amit Lotan, Leonard Lerer, Bernard Lerer, Tzuri Lifschytz. Effect of chemically synthesized psilocybin and psychedelic mushroom extract on molecular and metabolic profiles in mouse brain. Molecular Psychiatry 2024, 29 (7) , 2059-2073. https://doi.org/10.1038/s41380-024-02477-w
    11. Jan Thomann, Karolina E. Kolaczynska, Oliver V. Stoeckmann, Deborah Rudin, Patrick Vizeli, Marius C. Hoener, Christopher R. Pryce, Franz X. Vollenweider, Matthias E. Liechti, Urs Duthaler. In vitro and in vivo metabolism of psilocybin’s active metabolite psilocin. Frontiers in Pharmacology 2024, 15 https://doi.org/10.3389/fphar.2024.1391689
    12. Marco Pepe, Mohsen Hesami, Karla A. de la Cerda, Melissa L. Perreault, Tom Hsiang, Andrew Maxwell Phineas Jones. A journey with psychedelic mushrooms: From historical relevance to biology, cultivation, medicinal uses, biotechnology, and beyond. Biotechnology Advances 2023, 69 , 108247. https://doi.org/10.1016/j.biotechadv.2023.108247
    13. Paula Sophie Seibold, Stefanie Lawrinowitz, Ihar Raztsou, Markus Gressler, Hans-Dieter Arndt, Pierre Stallforth, Dirk Hoffmeister. Bifurcate evolution of quinone synthetases in basidiomycetes. Fungal Biology and Biotechnology 2023, 10 (1) https://doi.org/10.1186/s40694-023-00162-1
    14. Eike Schäfer, Paula S. Seibold, Stefan Bartram, Felix Trottmann, Veit G. Haensch, Markus Gressler, Andrew R. Chadeayne, Christian Hertweck, Sarah E. O'Connor, Dirk Hoffmeister. A „Magic Mushroom“ Multi‐Product Sesquiterpene Synthase. ChemBioChem 2023, 24 (21) https://doi.org/10.1002/cbic.202300511
    15. Raul Escamilla, María Eva González-Trujano, Jesús M. González Mariscal, Jesús Martín Torres-Valencia, Héctor Guzmán-González, José Luis Vega, Anja Loizaga-Velder. A Proposal to Study the Safety and Efficacy of Psilocybe cubensis in Preclinical and Clinical Studies as a Therapeutic Alternative for Major Depressive Disorder. Journal of Psychoactive Drugs 2023, 55 (5) , 570-580. https://doi.org/10.1080/02791072.2023.2246459
    16. Uroš Laban, Marilyn Naeem, Andrew R. Chadeayne, James A. Golen, David R. Manke. Synthesis and structure of 4-hydroxy- N -isopropyltryptamine (4-HO-NiPT) and its precursors. Acta Crystallographica Section E Crystallographic Communications 2023, 79 (4) , 280-286. https://doi.org/10.1107/S2056989023002098
    17. Hang Wang, Ying Wang. Matrix-assisted laser-desorption/ionization–mass spectrometric imaging of psilocybin and its analogues in psychedelic mushrooms using a cesium chloride-coated target plate. Analytical and Bioanalytical Chemistry 2023, 415 (4) , 735-745. https://doi.org/10.1007/s00216-022-04467-9
    18. Raphaël Serreau, Ammar Amirouche, Amine Benyamina, Sabine Berteina-Raboin. A Review of Synthetic Access to Therapeutic Compounds Extracted from Psilocybe. Pharmaceuticals 2023, 16 (1) , 40. https://doi.org/10.3390/ph16010040
    19. Alexander J. Bradshaw, Talia A. Backman, Virginia Ramírez-Cruz, Dale L. Forrister, Jaclyn M. Winter, Laura Guzmán-Dávalos, Giuliana Furci, Paul Stamets, Bryn T. M. Dentinger, . DNA Authentication and Chemical Analysis of Psilocybe Mushrooms Reveal Widespread Misdeterminations in Fungaria and Inconsistencies in Metabolites. Applied and Environmental Microbiology 2022, 88 (24) https://doi.org/10.1128/aem.01498-22
    20. Dominique Strauss, Soumya Ghosh, Zurika Murray, Marieka Gryzenhout. Psilocybin containing mushrooms: a rapidly developing biotechnology industry in the psychiatry, biomedical and nutraceutical fields. 3 Biotech 2022, 12 (12) https://doi.org/10.1007/s13205-022-03355-4
    21. Klára Gotvaldová, Jan Borovička, Kateřina Hájková, Petra Cihlářová, Alan Rockefeller, Martin Kuchař. Extensive Collection of Psychotropic Mushrooms with Determination of Their Tryptamine Alkaloids. International Journal of Molecular Sciences 2022, 23 (22) , 14068. https://doi.org/10.3390/ijms232214068
    22. Yi-Zhe Zhang, Ya-Ya Yan, Hai-Jiao Li, Yu-Guang Fan, Fei Xu. Toxin screening of Pseudosperma umbrinellum (Agaricals, Basidiomycota): First report of phalloidin in Inocybaceae mushroom. Toxicon 2022, 217 , 155-161. https://doi.org/10.1016/j.toxicon.2022.08.005
    23. Jesús G. Zorrilla, Antonio Evidente. Structures and Biological Activities of Alkaloids Produced by Mushrooms, a Fungal Subgroup. Biomolecules 2022, 12 (8) , 1025. https://doi.org/10.3390/biom12081025
    24. Sebastian Dörner, Kai Rogge, Janis Fricke, Tim Schäfer, Jacob M. Wurlitzer, Markus Gressler, Duyen N. K. Pham, David R. Manke, Andrew R. Chadeayne, Dirk Hoffmeister. Genetic Survey of Psilocybe Natural Products. ChemBioChem 2022, 23 (14) https://doi.org/10.1002/cbic.202200249
    25. Franco Della-Felice, Aloisio de Andrade Bartolomeu, Ronaldo Aloise Pilli. The phosphate ester group in secondary metabolites. Natural Product Reports 2022, 39 (5) , 1066-1107. https://doi.org/10.1039/D1NP00078K
    26. Soumia Teniou, Abderrahmane Bensegueni, Brooks M. Hybertson, Bifeng Gao, Swapan K. Bose, Joe M. McCord, Benoît Chovelon, Chawki Bensouici, Ahcène Boumendjel, Isabelle Hininger-Favier. Biodriven investigation of the wild edible mushroom Pleurotus eryngii revealing unique properties as functional food. Journal of Functional Foods 2022, 89 , 104965. https://doi.org/10.1016/j.jff.2022.104965
    27. Tolulope Bolaniran, Abdullahi Temitope Jamiu, Taofeeq Garuba, Alhassan Muhammad Wudil, Henry Ademola Adeola, Saheed Sabiu. An appraisal of the metabolites, pharmacological and biotechnological significance of edible mushrooms. Transactions of the Royal Society of South Africa 2021, 76 (3) , 257-272. https://doi.org/10.1080/0035919X.2021.1947921
    28. Klára Gotvaldová, Kateřina Hájková, Jan Borovička, Radek Jurok, Petra Cihlářová, Martin Kuchař. Stability of psilocybin and its four analogs in the biomass of the psychotropic mushroom Psilocybe cubensis. Drug Testing and Analysis 2021, 13 (2) , 439-446. https://doi.org/10.1002/dta.2950
    29. Claudius Lenz, Alexander Sherwood, Robert Kargbo, Dirk Hoffmeister. Taking Different Roads: l ‐Tryptophan as the Origin of Psilocybe Natural Products. ChemPlusChem 2021, 86 (1) , 28-35. https://doi.org/10.1002/cplu.202000581
    30. Janis Fricke, Robert Kargbo, Lars Regestein, Claudius Lenz, Gundela Peschel, Miriam A. Rosenbaum, Alexander Sherwood, Dirk Hoffmeister. Scalable Hybrid Synthetic/Biocatalytic Route to Psilocybin. Chemistry – A European Journal 2020, 26 (37) , 8281-8285. https://doi.org/10.1002/chem.202000134
    31. Richard Demmler, Janis Fricke, Sebastian Dörner, Markus Gressler, Dirk Hoffmeister. S ‐Adenosyl‐ l ‐Methionine Salvage Impacts Psilocybin Formation in “Magic” Mushrooms. ChemBioChem 2020, 21 (9) , 1364-1371. https://doi.org/10.1002/cbic.201900649
    32. Andrew R. Chadeayne, Duyen N. K. Pham, James A. Golen, David R. Manke. Bis(4-hydroxy- N -isopropyl- N -methyltryptammonium) fumarate: a new crystalline form of miprocin. Acta Crystallographica Section E Crystallographic Communications 2020, 76 (4) , 514-517. https://doi.org/10.1107/S2056989020002923
    33. Andrew R. Chadeayne, Duyen N. K. Pham, James A. Golen, David R. Manke. Norpsilocin: freebase and fumarate salt. Acta Crystallographica Section E Crystallographic Communications 2020, 76 (4) , 589-593. https://doi.org/10.1107/S2056989020004077
    34. Alexander M. Sherwood, Poncho Meisenheimer, Gary Tarpley, Robert B. Kargbo. An Improved, Practical, and Scalable Five-Step Synthesis of Psilocybin. Synthesis 2020, 52 (05) , 688-694. https://doi.org/10.1055/s-0039-1691565
    35. Felix Blei, Sebastian Dörner, Janis Fricke, Florian Baldeweg, Felix Trottmann, Anna Komor, Florian Meyer, Christian Hertweck, Dirk Hoffmeister. Simultaneous Production of Psilocybin and a Cocktail of β‐Carboline Monoamine Oxidase Inhibitors in “Magic” Mushrooms. Chemistry – A European Journal 2020, 26 (3) , 729-734. https://doi.org/10.1002/chem.201904363
    36. Nicole S. Jones, Jeffrey H. Comparin. Interpol review of controlled substances 2016–2019. Forensic Science International: Synergy 2020, 2 , 608-669. https://doi.org/10.1016/j.fsisyn.2020.01.019
    37. Janis Fricke, Claudius Lenz, Jonas Wick, Felix Blei, Dirk Hoffmeister. Production Options for Psilocybin: Making of the Magic. Chemistry – A European Journal 2019, 25 (4) , 897-903. https://doi.org/10.1002/chem.201802758
    38. Chia-Wei Phan, Elson Yi-Yong Tan, Vikineswary Sabaratnam. Bioactive Molecules in Edible and Medicinal Mushrooms for Human Wellness. 2019, 1597-1620. https://doi.org/10.1007/978-3-319-78030-6_83
    39. Richard P. Nugent, Crist N. Filer. Generation and use of tritiated borane in situ for formamide tritiation to an N‐methyl‐ 3 H group. Journal of Labelled Compounds and Radiopharmaceuticals 2018, 61 (10) , 805-808. https://doi.org/10.1002/jlcr.3624
    40. Chia-Wei Phan, Elson Yi-Yong Tan, Vikineswary Sabaratnam. Bioactive Molecules in Edible and Medicinal Mushrooms for Human Wellness. 2018, 1-24. https://doi.org/10.1007/978-3-319-54528-8_83-1

    Journal of Natural Products

    Cite this: J. Nat. Prod. 2017, 80, 10, 2835–2838
    Click to copy citationCitation copied!
    https://doi.org/10.1021/acs.jnatprod.7b00407
    Published September 20, 2017
    Copyright © 2017 The American Chemical Society and American Society of Pharmacognosy

    Article Views

    2684

    Altmetric

    -

    Citations

    Learn about these metrics

    Article Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.

    Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.

    The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated.