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Synthesis 2020; 52(05): 688-694
DOI: 10.1055/s-0039-1691565
psp
© Georg Thieme Verlag Stuttgart · New York

An Improved, Practical, and Scalable Five-Step Synthesis of Psilocybin

Alexander M. Sherwood
,
Poncho Meisenheimer
,
Gary Tarpley
,
Robert B. Kargbo  ∗
Further Information

Publication History

Received: 02 November 2019

Accepted after revision: 12 December 2019

Publication Date:
08 January 2020 (online)

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Abstract

Described herein is an improved synthesis of 3-[2-(dimethylamino)ethyl]-1H-indol-4-yl dihydrogen phosphate (psilocybin). The protocol outlines: synthesis of multigram quantities of psilocybin, identification of critical in-process parameters, and isolation of psilocybin without the use of chromatography, TLC, or aqueous workup. The synthesis furnishes psilocybin in five steps in 23% overall yield from an inexpensive acetoxyindole starting material. With specific focus on process control and impurity fate and removal, the improved procedure is amenable to providing high-quality psilocybin.

Key words

psilocybin - psilocin - phosphorylation - hydrogenolysis - reduction - quenching method - major depressive disorder

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/s-0039-1691565.
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