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Synthesis and In Vitro Profiling of Psilocin Derivatives : Improved Stability and Synthetic Properties

Eklund, Julia ; Bremberg, Ulf ; Larsson, Jessica ; Torkelsson, Edvard ; Wennerberg, Johan LU ; Zandelin, Symantha and Odell, Luke R. (2025) In Journal of Medicinal Chemistry 68(7). p.7153-7165
Abstract

As interest in using psilocybin therapy for treating mental health disorders intensifies, the need for efficient production methods becomes increasingly important. Current medical-grade psilocybin production is inefficient and relies on a complicated multistep synthesis. This study has explored and evaluated psilocin ester prodrugs and psilocin salts as potential alternatives to psilocybin, focusing on their ease of synthesis, chemical stability, and metabolic profiles. A diverse library of 15 psilocin ester prodrugs and six psilocin salts was synthesized and evaluated. The study successfully identified several psilocin ester prodrugs and psilocin salts that exhibited desirable characteristics, including storage and handling stability,... (More)

As interest in using psilocybin therapy for treating mental health disorders intensifies, the need for efficient production methods becomes increasingly important. Current medical-grade psilocybin production is inefficient and relies on a complicated multistep synthesis. This study has explored and evaluated psilocin ester prodrugs and psilocin salts as potential alternatives to psilocybin, focusing on their ease of synthesis, chemical stability, and metabolic profiles. A diverse library of 15 psilocin ester prodrugs and six psilocin salts was synthesized and evaluated. The study successfully identified several psilocin ester prodrugs and psilocin salts that exhibited desirable characteristics, including storage and handling stability, rapid metabolic conversion to psilocin, and easy synthesis, with potential advantages over psilocybin. This research introduces viable options through psilocin ester compounds and psilocin salts, offering promising avenues for future development.

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author
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Medicinal Chemistry
volume
68
issue
7
pages
13 pages
publisher
The American Chemical Society (ACS)
external identifiers
  • pmid:40108981
  • scopus:105000222846
ISSN
0022-2623
DOI
10.1021/acs.jmedchem.4c02612
language
English
LU publication?
yes
id
eda553f0-a4f1-4857-a99f-201ae6b5f2cd
date added to LUP
2026-01-12 13:05:19
date last changed
2026-01-13 03:00:18
@article{eda553f0-a4f1-4857-a99f-201ae6b5f2cd,
  abstract     = {{<p>As interest in using psilocybin therapy for treating mental health disorders intensifies, the need for efficient production methods becomes increasingly important. Current medical-grade psilocybin production is inefficient and relies on a complicated multistep synthesis. This study has explored and evaluated psilocin ester prodrugs and psilocin salts as potential alternatives to psilocybin, focusing on their ease of synthesis, chemical stability, and metabolic profiles. A diverse library of 15 psilocin ester prodrugs and six psilocin salts was synthesized and evaluated. The study successfully identified several psilocin ester prodrugs and psilocin salts that exhibited desirable characteristics, including storage and handling stability, rapid metabolic conversion to psilocin, and easy synthesis, with potential advantages over psilocybin. This research introduces viable options through psilocin ester compounds and psilocin salts, offering promising avenues for future development.</p>}},
  author       = {{Eklund, Julia and Bremberg, Ulf and Larsson, Jessica and Torkelsson, Edvard and Wennerberg, Johan and Zandelin, Symantha and Odell, Luke R.}},
  issn         = {{0022-2623}},
  language     = {{eng}},
  number       = {{7}},
  pages        = {{7153--7165}},
  publisher    = {{The American Chemical Society (ACS)}},
  series       = {{Journal of Medicinal Chemistry}},
  title        = {{Synthesis and In Vitro Profiling of Psilocin Derivatives : Improved Stability and Synthetic Properties}},
  url          = {{http://dx.doi.org/10.1021/acs.jmedchem.4c02612}},
  doi          = {{10.1021/acs.jmedchem.4c02612}},
  volume       = {{68}},
  year         = {{2025}},
}