{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T08:10:06Z","timestamp":1763021406129,"version":"3.45.0"},"reference-count":56,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2025,7,23]],"date-time":"2025-07-23T00:00:00Z","timestamp":1753228800000},"content-version":"vor","delay-in-days":22,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Archiv der Pharmazie"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Acyloxymethyl (ACOM) derivatives of tryptamines such as the psychedelic drug psilocin and the anti\u2010migraine drug sumatriptan bear potential as prodrugs. Previous synthetic approaches suffer from insufficient chemoselectivity between the desired functionalization of the phenolic (psilocin) or sulfonamide (sumatriptan) groups versus other reactive groups in the parent drugs. We report a novel synthetic route toward ACOM prodrugs of tryptamines via the chemoselective installation of a carbamate protecting group at the indole nitrogen by means of a Heller\u2013Sarpong reagent and final deprotection under extremely mild conditions. This enables delicate transformations such as the\n                    <jats:italic>O<\/jats:italic>\n                    \u2010acyloxymethylation of psilocin or the\n                    <jats:italic>N<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>2<\/jats:italic>\n                    <\/jats:sup>\n                    \u2010acyloxymethylation of sumatriptan. Several novel\n                    <jats:italic>O<\/jats:italic>\n                    \u2010ACOM ethers of hydroxytryptamines were obtained and evaluated in vitro for their potential as novel prodrugs for psychedelic therapy. The rate of bioactivation in human plasma may be adjusted to rapid (\n                    <jats:italic>t<\/jats:italic>\n                    <jats:sub>1\/2<\/jats:sub>\n                    \u2009&lt;\u20091\u2009min) or slow (\n                    <jats:italic>t<\/jats:italic>\n                    <jats:sub>1\/2<\/jats:sub>\n                    \u2009&gt;\u2009240\u2009min) kinetics by varying the acyl residue in the ACOM promoiety. Irrespective of the acyl residue, short half\u2010lives in human saliva will likely preclude the sublingual or buccal application of ACOM ether prodrugs of hydroxytryptamines, while other routes such as peroral, transdermal, nasal, or intravenous administration may be pursued.\n                  <\/jats:p>","DOI":"10.1002\/ardp.70022","type":"journal-article","created":{"date-parts":[[2025,7,24]],"date-time":"2025-07-24T06:25:56Z","timestamp":1753338356000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Efficient Acyloxymethylation of Psilocin and Other Tryptamines Yielding ACOM Prodrugs for Psychedelic\u2010Assisted Therapy"],"prefix":"10.1002","volume":"358","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-9105-3894","authenticated-orcid":false,"given":"Judith","family":"Stirn","sequence":"first","affiliation":[{"name":"Medicinal Chemistry, Institute of Pharmacy and Molecular Biotechnology IPMB Heidelberg University Heidelberg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3522-9182","authenticated-orcid":false,"given":"Christian D.","family":"Klein","sequence":"additional","affiliation":[{"name":"Medicinal Chemistry, Institute of Pharmacy and Molecular Biotechnology IPMB Heidelberg University Heidelberg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,7,23]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.9758\/cpn.23.1134"},{"key":"e_1_2_8_3_1","unstructured":"\u201cWorld Health Organization Model List of Essential Medicines: 22nd List (2021) \u201d Geneva World Health Organization https:\/\/iris.who.int\/handle\/10665\/345533."},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1517\/14656566.7.11.1503"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.317"},{"key":"e_1_2_8_5_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1468-2982.2002.00404.x"},{"key":"e_1_2_8_5_3","doi-asserted-by":"publisher","DOI":"10.1038\/s41386-023-01725-x"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0031-6865(97)00014-9"},{"key":"e_1_2_8_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.2821"},{"key":"e_1_2_8_6_3","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(94)90397-2"},{"key":"e_1_2_8_6_4","doi-asserted-by":"publisher","DOI":"10.1007\/BF00193709"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41386-019-0324-9"},{"key":"e_1_2_8_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0731-7085(96)01955-3"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/head.12181"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd.2018.46"},{"key":"e_1_2_8_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-024-00914-7"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/ardp.200700250"},{"key":"e_1_2_8_11_1","unstructured":"a)J.O'Meara H.Kaur andA. 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