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.2020 Jul 1;5(27):16959-16966.
doi: 10.1021/acsomega.0c02387. eCollection 2020 Jul 14.

Direct Phosphorylation of Psilocin Enables Optimized cGMP Kilogram-Scale Manufacture of Psilocybin

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Direct Phosphorylation of Psilocin Enables Optimized cGMP Kilogram-Scale Manufacture of Psilocybin

Robert B Kargbo et al. ACS Omega..

Abstract

A second-generation kilogram-scale synthesis of the psychedelic tryptamine psilocybin has been developed. The synthesis was designed to address several challenges first encountered with the scale-up of previously described literature procedures, which were not optimized for providing consistent yield and purity of products, atom economy, or being run in pilot plant-scale reactors. These challenges were addressed and circumvented with the design of the second-generation route, which featured an optimized cGMP large-scale Speeter-Anthony tryptamine synthesis to the intermediate psilocin with improved in-process control and impurity removal over the three steps. Psilocin was subsequently phosphorylated directly with phosphorous oxychloride for the first time, avoiding a tedious and poor atom economy benzyl-protecting group strategy common to all previously described methods for producing psilocybin. In this report, the challenges encountered in a 100 g scale first-generation literature-based synthesis are highlighted, followed by a detailed description of the newly developed second-generation synthesis to provide over one kilogram of high-purity psilocybin under cGMP.

Copyright © 2020 American Chemical Society.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Scheme 1
Scheme 1. First-Generation Multigram-Scale Synthesis of Psilocybin
Scheme 2
Scheme 2. Improved Second-Generation Synthesis of Psilocybin Utilizing Direct Phosphorylation
Scheme 3
Scheme 3. Direct Phosphorylation Showing intermediate7 and Plausible Mechanism of Formation of Characterized Pyrophosphate Minor Impurity10
See this image and copyright information in PMC

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References

    1. Sherwood A. M.; Prisinzano T. E. Novel Psychotherapeutics - A Cautiously Optimistic Focus on Hallucinogens. Expert Rev. Clin. Pharmacol. 2018, 11, 1–3. 10.1080/17512433.2018.1415755. - DOI - PMC - PubMed
    1. Johnson M. W.; Griffiths R. R. Potential therapeutic effects of psilocybin. Neurotherapeutics 2017, 14, 734–740. 10.1007/s13311-017-0542-y. - DOI - PMC - PubMed
    1. Carhart-Harris R. L.; Bolstridge M.; Rucker J.; Day C. M.; Erritzoe D.; Kaelen M.; Bloomfield M.; Rickard J. A.; Forbes B.; Feilding A.; et al. Psilocybin With Psychological Support For Treatment-Resistant Depression: An Open-Label Feasibility Study. Lancet Psychiat. 2016, 3, 619–627. 10.1016/S2215-0366(16)30065-7. - DOI - PubMed
    1. Griffiths R. R.; Johnson M. W.; Carducci M. A.; Umbricht A.; Richards W. A.; Richards B. D.; Cosimano M. P.; Klinedinst M. A. Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial. J. Psychopharmacol. 2016, 30, 1181–1197. 10.1177/0269881116675513. - DOI - PMC - PubMed
    1. Ross S.; Bossis A.; Guss J.; Agin-Liebes G.; Malone T.; Cohen B.; Mennenga S. E.; Belser A.; Kalliontzi K.; Babb J.; et al. Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial. J. Psychopharmacol. 2016, 30, 1165–1180. 10.1177/0269881116675512. - DOI - PMC - PubMed

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