{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T11:12:03Z","timestamp":1788261123902,"version":"build-2803163510"},"reference-count":51,"publisher":"Wiley","issue":"13","license":[{"start":{"date-parts":[[2022,5,18]],"date-time":"2022-05-18T00:00:00Z","timestamp":1652832000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["239748522-SFB 1127"],"award-info":[{"award-number":["239748522-SFB 1127"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemBioChem"],"published-print":{"date-parts":[[2022,7,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Psilocybin (<jats:bold>1<\/jats:bold>) is the major alkaloid found in psychedelic mushrooms and acts as a prodrug to psilocin (<jats:bold>2<\/jats:bold>, 4\u2010hydroxy\u2010<jats:italic>N<\/jats:italic>,<jats:italic>N<\/jats:italic>\u2010dimethyltryptamine), a potent psychedelic that exerts remarkable alteration of human consciousness. In contrast, the positional isomer bufotenin (<jats:bold>7<\/jats:bold>, 5\u2010hydroxy\u2010<jats:italic>N<\/jats:italic>,<jats:italic>N<\/jats:italic>\u2010dimethyltryptamine) differs significantly in its reported pharmacology. A series of experiments was designed to explore chemical differences between <jats:bold>2<\/jats:bold> and <jats:bold>7<\/jats:bold> and specifically to test the hypothesis that the C\u20104 hydroxy group of <jats:bold>2<\/jats:bold> significantly influences the observed physical and chemical properties through pseudo\u2010ring formation via an intramolecular hydrogen bond (IMHB). NMR spectroscopy, accompanied by quantum chemical calculations, was employed to compare hydrogen bond behavior in 4\u2010 and 5\u2010hydroxylated tryptamines. The results provide evidence for a pseudo\u2010ring in <jats:bold>2<\/jats:bold> and that sidechain\/hydroxyl interactions in 4\u2010hydroxytryptamines influence their oxidation kinetics. We conclude that the propensity to form IMHBs leads to a higher number of uncharged species that easily cross the blood\u2010brain barrier, compared to <jats:bold>7<\/jats:bold> and other 5\u2010hydroxytryptamines, which cannot form IMHBs. Our work helps understand a fundamental aspect of the pharmacology of <jats:bold>2<\/jats:bold> and should support efforts to introduce it (via the prodrug <jats:bold>1<\/jats:bold>) as an urgently needed therapeutic against major depressive disorder.<\/jats:p>","DOI":"10.1002\/cbic.202200183","type":"journal-article","created":{"date-parts":[[2022,4,28]],"date-time":"2022-04-28T15:58:48Z","timestamp":1651161528000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Assessment of Bioactivity\u2010Modulating Pseudo\u2010Ring Formation in Psilocin and Related Tryptamines"],"prefix":"10.1002","volume":"23","author":[{"given":"Claudius","family":"Lenz","sequence":"first","affiliation":[{"name":"Department Pharmaceutical Microbiology at the Hans Kn\u00f6ll Institute Friedrich-Schiller-Universit\u00e4t Jena  Beutenbergstrasse 11a 07745 Jena Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"D\u00f6rner","sequence":"additional","affiliation":[{"name":"Department Pharmaceutical Microbiology at the Hans Kn\u00f6ll Institute Friedrich-Schiller-Universit\u00e4t Jena  Beutenbergstrasse 11a 07745 Jena Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2587-7293","authenticated-orcid":false,"given":"Felix","family":"Trottmann","sequence":"additional","affiliation":[{"name":"Department Biomolecular Chemistry Leibniz Institute for Natural Product Research and Infection Biology Hans Kn\u00f6ll Institute  Beutenbergstrasse 11a 07745 Jena Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0367-337X","authenticated-orcid":false,"given":"Christian","family":"Hertweck","sequence":"additional","affiliation":[{"name":"Department Biomolecular Chemistry Leibniz Institute for Natural Product Research and Infection Biology Hans Kn\u00f6ll Institute  Beutenbergstrasse 11a 07745 Jena Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Sherwood","sequence":"additional","affiliation":[{"name":"The Usona Institute  2800 Woods Hollow Road Madison WI 53711 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5302-6461","authenticated-orcid":false,"given":"Dirk","family":"Hoffmeister","sequence":"additional","affiliation":[{"name":"Department Pharmaceutical Microbiology at the Hans Kn\u00f6ll Institute Friedrich-Schiller-Universit\u00e4t Jena  Beutenbergstrasse 11a 07745 Jena Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,5,18]]},"reference":[{"key":"e_1_2_7_1_1","doi-asserted-by":"publisher","DOI":"10.1002\/hlca.19590420518"},{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/chem.201802758"},{"key":"e_1_2_7_3_1","unstructured":"\u00a0"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.euroneuro.2013.12.006"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1021\/acsmedchemlett.0c00048"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41429-020-0311-8"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/cplu.202000581"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneurpsyc.1959.02340130141020"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/0028-3908(90)90001-8"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1080\/02791072.2001.10399925"},{"key":"e_1_2_7_11_1","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1016\/S0022-3565(24)36476-6","volume":"280","author":"Roth B. 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